WorldWideScience

Sample records for regulate sternal morphogenesis

  1. Sternal Tuberculosis

    African Journals Online (AJOL)

    TB) case load in immuno‑competent patients. Affliction of the skeletal system is rare with still rarer presentation of sternal osteomyelitis even in endemic countries. A patient with primary sternal TB presenting with multiple cutaneous sinuses over ...

  2. Sternal chondrosarcoma

    Directory of Open Access Journals (Sweden)

    Nelson Perelman Rosenberg

    2003-01-01

    Full Text Available Sternal neoplasms are extremely rare. It is difficult to make prospective evaluations due to the lack of consistent reports in the literature. The authors report the case of a woman in her seventies, who presented a chondrosarcoma of the sternum, treated by them.

  3. Sternal exploration or closure

    Science.gov (United States)

    VAC - vacuum-assisted closure - sternal wound; Sternal dehiscence; Sternal infection ... in the wound to look for signs of infection Remove dead or infected ... use a VAC (vacuum-assisted closure) dressing. It is a negative ...

  4. NFIX Regulates Neural Progenitor Cell Differentiation During Hippocampal Morphogenesis

    Science.gov (United States)

    Heng, Yee Hsieh Evelyn; McLeay, Robert C.; Harvey, Tracey J.; Smith, Aaron G.; Barry, Guy; Cato, Kathleen; Plachez, Céline; Little, Erica; Mason, Sharon; Dixon, Chantelle; Gronostajski, Richard M.; Bailey, Timothy L.; Richards, Linda J.; Piper, Michael

    2014-01-01

    Neural progenitor cells have the ability to give rise to neurons and glia in the embryonic, postnatal and adult brain. During development, the program regulating whether these cells divide and self-renew or exit the cell cycle and differentiate is tightly controlled, and imbalances to the normal trajectory of this process can lead to severe functional consequences. However, our understanding of the molecular regulation of these fundamental events remains limited. Moreover, processes underpinning development of the postnatal neurogenic niches within the cortex remain poorly defined. Here, we demonstrate that Nuclear factor one X (NFIX) is expressed by neural progenitor cells within the embryonic hippocampus, and that progenitor cell differentiation is delayed within Nfix−/− mice. Moreover, we reveal that the morphology of the dentate gyrus in postnatal Nfix−/− mice is abnormal, with fewer subgranular zone neural progenitor cells being generated in the absence of this transcription factor. Mechanistically, we demonstrate that the progenitor cell maintenance factor Sry-related HMG box 9 (SOX9) is upregulated in the hippocampus of Nfix−/− mice and demonstrate that NFIX can repress Sox9 promoter-driven transcription. Collectively, our findings demonstrate that NFIX plays a central role in hippocampal morphogenesis, regulating the formation of neuronal and glial populations within this structure. PMID:23042739

  5. Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons

    Directory of Open Access Journals (Sweden)

    Shan Meltzer

    2017-10-01

    Full Text Available Disruptions in lipid homeostasis have been observed in many neurodevelopmental disorders that are associated with dendrite morphogenesis defects. However, the molecular mechanisms of how lipid homeostasis affects dendrite morphogenesis are unclear. We find that easily shocked (eas, which encodes a kinase with a critical role in phospholipid phosphatidylethanolamine (PE synthesis, and two other enzymes in this synthesis pathway are required cell autonomously in sensory neurons for dendrite growth and stability. Furthermore, we show that the level of Sterol Regulatory Element-Binding Protein (SREBP activity is important for dendrite development. SREBP activity increases in eas mutants, and decreasing the level of SREBP and its transcriptional targets in eas mutants largely suppresses the dendrite growth defects. Furthermore, reducing Ca2+ influx in neurons of eas mutants ameliorates the dendrite morphogenesis defects. Our study uncovers a role for EAS kinase and reveals the in vivo function of phospholipid homeostasis in dendrite morphogenesis.

  6. Melatonin Inhibits Embryonic Salivary Gland Branching Morphogenesis by Regulating Both Epithelial Cell Adhesion and Morphology

    Science.gov (United States)

    Miura, Jiro; Sakai, Manabu; Uchida, Hitoshi; Nakamura, Wataru; Nohara, Kanji; Maruyama, Yusuke; Hattori, Atsuhiko; Sakai, Takayoshi

    2015-01-01

    Many organs, including salivary glands, lung, and kidney, are formed by epithelial branching during embryonic development. Branching morphogenesis occurs via either local outgrowths or the formation of clefts that subdivide epithelia into buds. This process is promoted by various factors, but the mechanism of branching morphogenesis is not fully understood. Here we have defined melatonin as a potential negative regulator or “brake” of branching morphogenesis, shown that the levels of it and its receptors decline when branching morphogenesis begins, and identified the process that it regulates. Melatonin has various physiological functions, including circadian rhythm regulation, free-radical scavenging, and gonadal development. Furthermore, melatonin is present in saliva and may have an important physiological role in the oral cavity. In this study, we found that the melatonin receptor is highly expressed on the acinar epithelium of the embryonic submandibular gland. We also found that exogenous melatonin reduces salivary gland size and inhibits branching morphogenesis. We suggest that this inhibition does not depend on changes in either proliferation or apoptosis, but rather relates to changes in epithelial cell adhesion and morphology. In summary, we have demonstrated a novel function of melatonin in organ formation during embryonic development. PMID:25876057

  7. Regulation of Epithelial Morphogenesis by the G-Protein Coupled Receptor Mist and its Ligand Fog*

    Science.gov (United States)

    Manning, Alyssa J.; Peters, Kimberly A.; Peifer, Mark; Rogers, Stephen L.

    2014-01-01

    Epithelial morphogenesis is essential for shaping organs and tissues and for establishment of the three embryonic germ layers during gastrulation. Studies of gastrulation in Drosophila have provided insight into how epithelial morphogenesis is governed by developmental patterning mechanisms. We developed an assay to recapitulate morphogenetic shape changes in individual cultured cells, and used RNAi-based screening to identify Mist, a Drosophila G protein-coupled receptor (GPCR) that transduces signals from the secreted ligand Folded gastrulation (Fog) in cultured cells. Mist functioned in Fog-dependent embryonic morphogenesis, and the transcription factor Snail regulated expression of mist in zygotes. Our data revealed how a cell fate transcriptional program acts through a ligand-GPCR pair to stimulate epithelial morphogenetic shape changes. PMID:24222713

  8. MicroRNA miR-328 regulates zonation morphogenesis by targeting CD44 expression.

    Science.gov (United States)

    Wang, Chia-Hui; Lee, Daniel Y; Deng, Zhaoqun; Jeyapalan, Zina; Lee, Shao-Chen; Kahai, Shireen; Lu, Wei-Yang; Zhang, Yaou; Yang, Burton B

    2008-06-18

    Morphogenesis is crucial to initiate physiological development and tumor invasion. Here we show that a microRNA controls zonation morphogenesis by targeting hyaluronan receptor CD44. We have developed a novel system to study microRNA functions by generating constructs expressing pre-miRNAs and mature miRNAs. Using this system, we have demonstrated that expression of miR-328 reduced cell adhesion, aggregation, and migration, and regulated formation of capillary structure. Protein analysis indicated that miR-328 repressed CD44 expression. Activities of luciferase constructs harboring the target site in CD44, but not the one containing mutation, were repressed by miR-328. Zonation morphogenesis appeared in cells transfected by miR-328: miR-328-transfected cells were present on the surface of zonating structures while the control cells stayed in the middle. MiR-328-mediated CD44 actions was validated by anti-CD44 antibody, hyaluronidase, CD44 siRNA, and CD44 expression constructs. In vivo experiments showed that CD44-silencing cells appeared as layers on the surfaces of nodules or zonating structures. Immuno-histochemistry also exhibited CD44-negative cells on the surface layers of normal rat livers and the internal zones of Portal veins. Our results demonstrate that miR-328 targets CD44, which is essential in regulating zonation morphogenesis: silencing of CD44 expression is essential in sealing the zonation structures to facilitate their extension and to inhibit complex expansion.

  9. S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

    Science.gov (United States)

    Fang, Chao; Bian, Ganlan; Ren, Pan; Xiang, Jie; Song, Jun; Yu, Caiyong; Zhang, Qian; Liu, Ling; Chen, Kun; Liu, Fangfang; Zhang, Kun; Wu, Chunfeng; Sun, Ruixia; Hu, Dan; Ju, Gong; Wang, Jian

    2018-02-08

    Spinster homolog 2 (SPNS2) is the membrane transporter of sphingosine-1-phosphate (S1P), and it participates in several physiologic processes by activating different S1P receptors (S1PRs). However, its functions in the nervous system remain largely unclear. We explored the important role of SPNS2 in the process of retinal morphogenesis using a spns2-deficient rat model. In the absence of the functional SPNS2 transporter, we observed progressively aggravating laminar disorganization of the epithelium at the postnatal stage of retinal development. Disrupted cell polarity, delayed cell-cycle exit of retinal progenitor cells, and insufficient migration of newborn neurons were proposed in this study as potential mechanisms accounting for this structural disorder. In addition, we analyzed the expression profiles of spns2 and s1prs, and proposed that SPNS2 regulated retinal morphogenesis by establishing the S1P level in the eye and activating S1PR3 signaling. These data indicate that SPNS2 is indispensable for normal retinal morphogenesis and provide new insights on the role of S1P in the developing retina using an established in vivo model.-Fang, C., Bian, G., Ren, P., Xiang, J., Song, J., Yu, C., Zhang, Q., Liu, L., Chen, K., Liu, F., Zhang, K., Wu, C., Sun, R., Hu, D., Ju, G., Wang, J. S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

  10. SACE_0012, a TetR-Family Transcriptional Regulator, Affects the Morphogenesis of Saccharopolyspora erythraea

    OpenAIRE

    Yin, Xiaojuan; Xu, Xinqiang; Wu, Hang; Yuan, Li; Huang, Xunduan; Zhang, Buchang

    2013-01-01

    Saccharopolyspora erythraea, a mycelium-forming actinomycete, produces a clinically important antibiotic erythromycin. Extensive investigations have provided insights into erythromycin biosynthesis in S. erythraea, but knowledge of its morphogenesis remains limited. By gene inactivation and complementation strategies, the TetR-family transcriptional regulator SACE_0012 was identified to be a negative regulator of mycelium formation of S. erythraea A226. Detected by quantitative real-time PCR,...

  11. Shape self-regulation in early lung morphogenesis.

    Directory of Open Access Journals (Sweden)

    Raphaël Clément

    Full Text Available The arborescent architecture of mammalian conductive airways results from the repeated branching of lung endoderm into surrounding mesoderm. Subsequent lung's striking geometrical features have long raised the question of developmental mechanisms involved in morphogenesis. Many molecular actors have been identified, and several studies demonstrated the central role of Fgf10 and Shh in growth and branching. However, the actual branching mechanism and the way branching events are organized at the organ scale to achieve a self-avoiding tree remain to be understood through a model compatible with evidenced signaling. In this paper we show that the mere diffusion of FGF10 from distal mesenchyme involves differential epithelial proliferation that spontaneously leads to branching. Modeling FGF10 diffusion from sub-mesothelial mesenchyme where Fgf10 is known to be expressed and computing epithelial and mesenchymal growth in a coupled manner, we found that the resulting laplacian dynamics precisely accounts for the patterning of FGF10-induced genes, and that it spontaneously involves differential proliferation leading to a self-avoiding and space-filling tree, through mechanisms that we detail. The tree's fine morphological features depend on the epithelial growth response to FGF10, underlain by the lung's complex regulatory network. Notably, our results suggest that no branching information has to be encoded and that no master routine is required to organize branching events at the organ scale. Despite its simplicity, this model identifies key mechanisms of lung development, from branching to organ-scale organization, and could prove relevant to the development of other branched organs relying on similar pathways.

  12. SACE_0012, a TetR-family transcriptional regulator, affects the morphogenesis of Saccharopolyspora erythraea.

    Science.gov (United States)

    Yin, Xiaojuan; Xu, Xinqiang; Wu, Hang; Yuan, Li; Huang, Xunduan; Zhang, Buchang

    2013-12-01

    Saccharopolyspora erythraea, a mycelium-forming actinomycete, produces a clinically important antibiotic erythromycin. Extensive investigations have provided insights into erythromycin biosynthesis in S. erythraea, but knowledge of its morphogenesis remains limited. By gene inactivation and complementation strategies, the TetR-family transcriptional regulator SACE_0012 was identified to be a negative regulator of mycelium formation of S. erythraea A226. Detected by quantitative real-time PCR, the relative transcription of SACE_7115, the amfC homolog for an aerial mycelium formation protein, was dramatically increased in SACE_0012 mutant, whereas erythromycin biosynthetic gene eryA, a pleiotropic regulatory gene bldD, and the genes SACE_2141, SACE_6464, SACE_6040, that are the homologs to the sporulation regulators WhiA, WhiB, WhiG, were not differentially expressed. SACE_0012 disruption could not restore its defect of aerial development in bldD mutant, and also did not further accelerate the mycelium formation in the mutant of SACE_7040 gene, that was previously identified to be a morphogenesis repressor. Furthermore, the transcriptional level of SACE_0012 had not markedly changed in bldD and SACE_7040 mutant over A226. Taken together, these results suggest that SACE_0012 is a negative regulator of S. erythraea morphogenesis by mainly increasing the transcription of amfC gene, independently of the BldD regulatory system.

  13. A novel ALS-associated variant in UBQLN4 regulates motor axon morphogenesis

    Science.gov (United States)

    Edens, Brittany M; Yan, Jianhua; Miller, Nimrod; Deng, Han-Xiang; Siddique, Teepu; Ma, Yongchao C

    2017-01-01

    The etiological underpinnings of amyotrophic lateral sclerosis (ALS) are complex and incompletely understood, although contributions to pathogenesis by regulators of proteolytic pathways have become increasingly apparent. Here, we present a novel variant in UBQLN4 that is associated with ALS and show that its expression compromises motor axon morphogenesis in mouse motor neurons and in zebrafish. We further demonstrate that the ALS-associated UBQLN4 variant impairs proteasomal function, and identify the Wnt signaling pathway effector beta-catenin as a UBQLN4 substrate. Inhibition of beta-catenin function rescues the UBQLN4 variant-induced motor axon phenotypes. These findings provide a strong link between the regulation of axonal morphogenesis and a new ALS-associated gene variant mediated by protein degradation pathways. DOI: http://dx.doi.org/10.7554/eLife.25453.001 PMID:28463112

  14. Bmp signaling mediates endoderm pouch morphogenesis by regulating Fgf signaling in zebrafish

    Science.gov (United States)

    Swartz, Mary E.; McCarthy, Neil; Norrie, Jacqueline L.; Eberhart, Johann K.

    2016-01-01

    The endodermal pouches are a series of reiterated structures that segment the pharyngeal arches and help pattern the vertebrate face. Multiple pathways regulate the complex process of endodermal development, including the Bone morphogenetic protein (Bmp) pathway. However, the role of Bmp signaling in pouch morphogenesis is poorly understood. Using genetic and chemical inhibitor approaches, we show that pouch morphogenesis requires Bmp signaling from 10-18 h post-fertilization, immediately following gastrulation. Blocking Bmp signaling during this window results in morphological defects to the pouches and craniofacial skeleton. Using genetic chimeras we show that Bmp signals directly to the endoderm for proper morphogenesis. Time-lapse imaging and analysis of reporter transgenics show that Bmp signaling is necessary for pouch outpocketing via the Fibroblast growth factor (Fgf) pathway. Double loss-of-function analyses demonstrate that Bmp and Fgf signaling interact synergistically in craniofacial development. Collectively, our analyses shed light on the tissue and signaling interactions that regulate development of the vertebrate face. PMID:27122171

  15. MicroRNA miR-328 regulates zonation morphogenesis by targeting CD44 expression.

    Directory of Open Access Journals (Sweden)

    Chia-Hui Wang

    Full Text Available Morphogenesis is crucial to initiate physiological development and tumor invasion. Here we show that a microRNA controls zonation morphogenesis by targeting hyaluronan receptor CD44. We have developed a novel system to study microRNA functions by generating constructs expressing pre-miRNAs and mature miRNAs. Using this system, we have demonstrated that expression of miR-328 reduced cell adhesion, aggregation, and migration, and regulated formation of capillary structure. Protein analysis indicated that miR-328 repressed CD44 expression. Activities of luciferase constructs harboring the target site in CD44, but not the one containing mutation, were repressed by miR-328. Zonation morphogenesis appeared in cells transfected by miR-328: miR-328-transfected cells were present on the surface of zonating structures while the control cells stayed in the middle. MiR-328-mediated CD44 actions was validated by anti-CD44 antibody, hyaluronidase, CD44 siRNA, and CD44 expression constructs. In vivo experiments showed that CD44-silencing cells appeared as layers on the surfaces of nodules or zonating structures. Immuno-histochemistry also exhibited CD44-negative cells on the surface layers of normal rat livers and the internal zones of Portal veins. Our results demonstrate that miR-328 targets CD44, which is essential in regulating zonation morphogenesis: silencing of CD44 expression is essential in sealing the zonation structures to facilitate their extension and to inhibit complex expansion.

  16. Auxin and plant morphogenesis - a model of regulation

    Directory of Open Access Journals (Sweden)

    Stefan Zajączkowski

    2015-01-01

    Full Text Available In the presented model cells of the plant body form a spatial medium in which three-dimensional morphogenic waves of auxin are propagated. Points in the same phase of oscillation form isophasic surfaces and the vectors of wave propagation form a three-dimensional vector field. The vectors in the case of local inhomogeneities of the medium deviate from organ polarity, providing positional information recognized by cells. Models of functioning of such a supracellular oscillatory system in regulation of tissue differentiation, tropic responses and plant form are discussed.

  17. the role of plant growth regulators in morphogenesis

    Directory of Open Access Journals (Sweden)

    A. Mujib

    2018-01-01

    Full Text Available Althaea officinalis L. (marshmallow belonging to the Malvaceae family, is an important plant that contains a variety of important phytocompounds including asparagine, pectin, flavonoids, polyphenolic acid, and scopoletin. The yield of these compounds can be improved using biotechnological methods that allow for a steady and continuous regeneration of plant material. To the best of our knowledge, thus far, the In vitro clonal multiplication of marshmallow has not been attempted on a large scale. Therefore, in this study, we developed callus induction and multiple shoot regeneration protocols from explants. All the explants, i.e., roots, nodes, and leaves, evoked compact white or yellow calli in a medium supplemented with 2,4-dichlorophenoxyacetic acid (2,4-D, which grew vigorously. The callus induction frequency was the highest (62.1% from stem nodes, followed by leaves (39.1% and roots (27.5%. The differential behavior of explants in response to various plant growth regulators (PGRs was studied. The calli from leaves and roots were noted to be non-organogenic/embryogenic in media containing different PGR concentrations and have been described in this communication. The stem nodes used were cultured on MS media amended with different concentrations of benzyl-amino-purine (BAP: 0.5, 1.0, and 2.0 mg/l. Multiple shoots were formed at variable numbers, the maximum being in a medium supplemented with 1.0 mg/l of BAP. The induced shoots were rooted in IBA-, NAA-, and IAA-amended media, where IBA at 0.5 mg/l induced a maximum number of roots (8.8 roots/shoot. The regenerated plants were transferred to plastic pots, filled with soilrite and soil (1 : 1, and finally, transferred to outdoor conditions.

  18. CDKL5, a protein associated with rett syndrome, regulates neuronal morphogenesis via Rac1 signaling.

    Science.gov (United States)

    Chen, Qian; Zhu, Yong-Chuan; Yu, Jing; Miao, Sheng; Zheng, Jing; Xu, Li; Zhou, Yang; Li, Dan; Zhang, Chi; Tao, Jiong; Xiong, Zhi-Qi

    2010-09-22

    Mutations in cyclin-dependent kinase-like 5 (CDKL5), also known as serine/threonine kinase 9 (STK9), have been identified in patients with Rett syndrome (RTT) and X-linked infantile spasm. However, the function of CDKL5 in the brain remains unknown. Here, we report that CDKL5 is a critical regulator of neuronal morphogenesis. We identified a neuron-specific splicing variant of CDKL5 whose expression was markedly induced during postnatal development of the rat brain. Downregulating CDKL5 by RNA interference (RNAi) in cultured cortical neurons inhibited neurite growth and dendritic arborization, whereas overexpressing CDKL5 had opposite effects. Furthermore, knocking down CDKL5 in the rat brain by in utero electroporation resulted in delayed neuronal migration, and severely impaired dendritic arborization. In contrast to its proposed function in the nucleus, we found that CDKL5 regulated dendrite development through a cytoplasmic mechanism. In fibroblasts and in neurons, CDKL5 colocalized and formed a protein complex with Rac1, a critical regulator of actin remodeling and neuronal morphogenesis. Overexpression of Rac1 prevented the inhibition of dendrite growth caused by CDKL5 knockdown, and the growth-promoting effect of ectopically expressed CDKL5 on dendrites was abolished by coexpressing a dominant-negative form of Rac1. Moreover, CDKL5 was required for brain-derived neurotrophic factor (BDNF)-induced activation of Rac1. Together, these results demonstrate a critical role of CDKL5 in neuronal morphogenesis and identify a Rho GTPase signaling pathway which may contribute to CDKL5-related disorders.

  19. Hypoxia-inducible factor 1α regulates branching morphogenesis during kidney development.

    Science.gov (United States)

    Tsuji, Kenji; Kitamura, Shinji; Makino, Hirofumi

    2014-04-25

    The kidneys are exposed to hypoxic conditions during development. Hypoxia-inducible factor (HIF), an important mediator of the response to hypoxia, is believed to have an important role in development. However, the relationship between HIF and branching morphogenesis has not been elucidated clearly. In this study, we examined whether HIF regulates kidney development. We harvested kidneys from day 13 rat embryos (E13Ks) and cultured the organs under normoxic (20% O2/5% CO2) or hypoxic (5% O2/5% CO2) conditions. We evaluated the kidneys based on morphology and gene expression. E13Ks cultured under hypoxic conditions had significantly more ureteric bud (UB) branching than the E13Ks cultured under normoxic conditions. In addition, the mRNA levels of GDNF and GDNF receptor (GFR-α1), increased under hypoxic conditions in E13Ks. When we cultured E13Ks with the HIF-1α inhibitor digoxin or with siRNA targeting HIF-1α under hypoxic conditions, we did not observe increased UB branching. In addition, the expression of GDNF and GFR-α1 was inhibited under hypoxic conditions when the kidneys were treated with siRNA targeting HIF-1α. We also elucidated that hypoxia inhibited UB cell apoptosis and promoted the expression of FGF7 mRNA levels in metanephric mesenchymal (MM) cells in vitro. These findings suggest that hypoxic condition has important roles in inducing branching morphogenesis during kidney development. Hypoxia might mediate branching morphogenesis via not only GDNF/Ret but also FGF signaling pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Canonical TGF-β Signaling Negatively Regulates Neuronal Morphogenesis through TGIF/Smad Complex-Mediated CRMP2 Suppression.

    Science.gov (United States)

    Nakashima, Hideyuki; Tsujimura, Keita; Irie, Koichiro; Ishizu, Masataka; Pan, Miao; Kameda, Tomonori; Nakashima, Kinichi

    2018-05-16

    Functional neuronal connectivity requires proper neuronal morphogenesis and its dysregulation causes neurodevelopmental diseases. Transforming growth factor-β (TGF-β) family cytokines play pivotal roles in development, but little is known about their contribution to morphological development of neurons. Here we show that the Smad-dependent canonical signaling of TGF-β family cytokines negatively regulates neuronal morphogenesis during brain development. Mechanistically, activated Smads form a complex with transcriptional repressor TG-interacting factor (TGIF), and downregulate the expression of a neuronal polarity regulator, collapsin response mediator protein 2. We also demonstrate that TGF-β family signaling inhibits neurite elongation of human induced pluripotent stem cell-derived neurons. Furthermore, the expression of TGF-β receptor 1, Smad4, or TGIF, which have mutations found in patients with neurodevelopmental disorders, disrupted neuronal morphogenesis in both mouse (male and female) and human (female) neurons. Together, these findings suggest that the regulation of neuronal morphogenesis by an evolutionarily conserved function of TGF-β signaling is involved in the pathogenesis of neurodevelopmental diseases. SIGNIFICANCE STATEMENT Canonical transforming growth factor-β (TGF-β) signaling plays a crucial role in multiple organ development, including brain, and mutations in components of the signaling pathway associated with several human developmental disorders. In this study, we found that Smads/TG-interacting factor-dependent canonical TGF-β signaling regulates neuronal morphogenesis through the suppression of collapsin response mediator protein-2 (CRMP2) expression during brain development, and that function of this signaling is evolutionarily conserved in the mammalian brain. Mutations in canonical TGF-β signaling factors identified in patients with neurodevelopmental disorders disrupt the morphological development of neurons. Thus, our

  1. A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis

    NARCIS (Netherlands)

    Siegel, Gabriele; Obernosterer, Gregor; Fiore, Roberto; Oehmen, Martin; Bicker, Silvia; Christensen, Mette; Khudayberdiev, Sharof; Leuschner, Philipp F; Busch, Clara J L; Kane, Christina; Hübel, Katja; Dekker, Frank; Hedberg, Christian; Rengarajan, Balamurugan; Drepper, Carsten; Waldmann, Herbert; Kauppinen, Sakari; Greenberg, Michael E; Draguhn, Andreas; Rehmsmeier, Marc; Martinez, Javier; Schratt, Gerhard M; Dekker, Frank

    The microRNA pathway has been implicated in the regulation of synaptic protein synthesis and ultimately in dendritic spine morphogenesis, a phenomenon associated with long-lasting forms of memory. However, the particular microRNAs (miRNAs) involved are largely unknown. Here we identify specific

  2. The microRNA-200 family coordinately regulates cell adhesion and proliferation in hair morphogenesis.

    Science.gov (United States)

    Hoefert, Jaimee E; Bjerke, Glen A; Wang, Dongmei; Yi, Rui

    2018-06-04

    The microRNA (miRNA)-200 (miR-200) family is highly expressed in epithelial cells and frequently lost in metastatic cancer. Despite intensive studies into their roles in cancer, their targets and functions in normal epithelial tissues remain unclear. Importantly, it remains unclear how the two subfamilies of the five-miRNA family, distinguished by a single nucleotide within the seed region, regulate their targets. By directly ligating miRNAs to their targeted mRNA regions, we identify numerous miR-200 targets involved in the regulation of focal adhesion, actin cytoskeleton, cell cycle, and Hippo/Yap signaling. The two subfamilies bind to largely distinct target sites, but many genes are coordinately regulated by both subfamilies. Using inducible and knockout mouse models, we show that the miR-200 family regulates cell adhesion and orientation in the hair germ, contributing to precise cell fate specification and hair morphogenesis. Our findings demonstrate that combinatorial targeting of many genes is critical for miRNA function and provide new insights into miR-200's functions. © 2018 Hoefert et al.

  3. Sternal fractures and their management

    Directory of Open Access Journals (Sweden)

    Al-achraf Khoriati

    2013-01-01

    Full Text Available Sternal fractures are predominantly associated with deceleration injuries and blunt anterior chest trauma. Sternal trauma must be carefully evaluated by monitoring of vital parameters and it is of paramount importance that concomitant injuries are excluded. Nevertheless, routine admission of patients with isolated sternal fractures for observation is still common in today′s practice, which is often unnecessary. This article aims to describe the prognosis, the recommended assessment and management of patients with sternal fractures, to help clinicians make an evidence-based judgment regarding the need for hospitalization.

  4. Inwardly rectifying potassium channels influence Drosophila wing morphogenesis by regulating Dpp release.

    Science.gov (United States)

    Dahal, Giri Raj; Pradhan, Sarala Joshi; Bates, Emily Anne

    2017-08-01

    Loss of embryonic ion channel function leads to morphological defects, but the underlying reason for these defects remains elusive. Here, we show that inwardly rectifying potassium (Irk) channels regulate release of the Drosophila bone morphogenetic protein Dpp in the developing fly wing and that this is necessary for developmental signaling. Inhibition of Irk channels decreases the incidence of distinct Dpp-GFP release events above baseline fluorescence while leading to a broader distribution of Dpp-GFP. Work by others in different cell types has shown that Irk channels regulate peptide release by modulating membrane potential and calcium levels. We found calcium transients in the developing wing, and inhibition of Irk channels reduces the duration and amplitude of calcium transients. Depolarization with high extracellular potassium evokes Dpp release. Taken together, our data implicate Irk channels as a requirement for regulated release of Dpp, highlighting the importance of the temporal pattern of Dpp presentation for morphogenesis of the wing. © 2017. Published by The Company of Biologists Ltd.

  5. Mutations in TSPEAR, Encoding a Regulator of Notch Signaling, Affect Tooth and Hair Follicle Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Alon Peled

    2016-10-01

    Full Text Available Despite recent advances in our understanding of the pathogenesis of ectodermal dysplasias (EDs, the molecular basis of many of these disorders remains unknown. In the present study, we aimed at elucidating the genetic basis of a new form of ED featuring facial dysmorphism, scalp hypotrichosis and hypodontia. Using whole exome sequencing, we identified 2 frameshift and 2 missense mutations in TSPEAR segregating with the disease phenotype in 3 families. TSPEAR encodes the thrombospondin-type laminin G domain and EAR repeats (TSPEAR protein, whose function is poorly understood. TSPEAR knock-down resulted in altered expression of genes known to be regulated by NOTCH and to be involved in murine hair and tooth development. Pathway analysis confirmed that down-regulation of TSPEAR in keratinocytes is likely to affect Notch signaling. Accordingly, using a luciferase-based reporter assay, we showed that TSPEAR knock-down is associated with decreased Notch signaling. In addition, NOTCH1 protein expression was reduced in patient scalp skin. Moreover, TSPEAR silencing in mouse hair follicle organ cultures was found to induce apoptosis in follicular epithelial cells, resulting in decreased hair bulb diameter. Collectively, these observations indicate that TSPEAR plays a critical, previously unrecognized role in human tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway.

  6. Spatial organization of adhesion: force-dependent regulation and function in tissue morphogenesis

    OpenAIRE

    Papusheva, Ekaterina; Heisenberg, Carl-Philipp

    2010-01-01

    The Heisenberg laboratory reviews the spatial organization of signalling complexes at cell–matrix and cell–cell contact sites and its impact on cell integrity, cellular polarity and tissue morphogenesis.

  7. bullwinkle and shark regulate dorsal-appendage morphogenesis in Drosophila oogenesis.

    Science.gov (United States)

    Tran, David H; Berg, Celeste A

    2003-12-01

    bullwinkle (bwk) regulates embryonic anteroposterior patterning and, through a novel germline-to-soma signal, morphogenesis of the eggshell dorsal appendages. We screened for dominant modifiers of the bullwinkle mooseantler eggshell phenotype and identified shark, which encodes an SH2-domain, ankyrin-repeat tyrosine kinase. At the onset of dorsal-appendage formation, shark is expressed in a punctate pattern in the squamous stretch cells overlying the nurse cells. Confocal microscopy with cell-type-specific markers demonstrates that the stretch cells act as a substrate for the migrating dorsal-appendage-forming cells and extend cellular projections towards them. Mosaic analyses reveal that shark is required in follicle cells for cell migration and chorion deposition. Proper shark RNA expression in the stretch cells requires bwk activity, while restoration of shark expression in the stretch cells suppresses the bwk dorsal-appendage phenotype. These results suggest that shark plays an important downstream role in the bwk-signaling pathway. Candidate testing implicates Src42A in a similar role, suggesting conservation with a vertebrate signaling pathway involving non-receptor tyrosine kinases.

  8. Theoretical study of Beloussov's hyper-restoration hypothesis for mechanical regulation of morphogenesis.

    Science.gov (United States)

    Taber, Larry A

    2008-12-01

    Computational models were used to explore the idea that morphogenesis is regulated, in part, by feedback from mechanical stress according to Beloussov's hyper-restoration (HR) hypothesis. According to this hypothesis, active tissue responses to stress perturbations tend to restore, but overshoot, the original (target) stress. To capture this behavior, the rate of growth or contraction is assumed to depend on the difference between the current and target stresses. Stress overshoot is obtained by letting the target stress change at a rate proportional to the same stress difference. The feasibility of the HR hypothesis is illustrated by models for stretching of epithelia, cylindrical bending of plates, invagination of cylindrical and spherical shells, and early amphibian development. In each case, an initial perturbation leads to an active mechanical response that changes the form of the tissue. The results show that some morphogenetic processes can be entirely self-driven by HR responses once they are initiated (possibly by genetic activity). Other processes, however, may require secondary mechanisms or perturbations to proceed to completion.

  9. Cross-talk between light and glucose regulation controls toxin production and morphogenesis in Aspergillus nidulans

    International Nuclear Information System (INIS)

    Atoui, A.; Larey, C.; Thokala, R.; Calvo, A.M.; Kastner, C.; Fischer, R.; Etxebeste, O; Espeso, E.A.

    2010-01-01

    Light is a major environmental stimulus that has a broad effect on organisms, triggering a cellular response that results in an optimal adaptation enhancing fitness and survival. In fungi, light affects growth, and causes diverse morphological changes such as those leading to reproduction. Light can also affect fungal metabolism, including the biosynthesis of natural products. In this study we show that in Aspergillus nidulans the effect of light on the production of the sterigmatocystin (ST) toxin depends on the glucose concentration. In cultures grown with 1% glucose and exposed to light, ST production was lower than when grown in the dark. This lower ST production coincided with an elevated rate of cellular damage with partial loss of nuclear integrity and vacuolated cytoplasm. However, in cultures grown with 2% glucose these effects were reversed and light enhanced ST production. Glucose abundance also affected the light-dependent subcellular localization of the VeA (velvet) protein, a key regulator necessary for normal light-dependent morphogenesis and secondary metabolism in Aspergilli and other fungal gen- era. The role of other VeA-associated proteins, particularly the blue-light-sensing proteins LreA and LreB (WC-1 and WC-2 orthologs), on conidiation could also be modified by the abundance of glucose. We also show that LreA and LreB, as well as the phytochrome FphA, modulate not only the synthesis of sterigmat- ocystin, but also the production of the antibiotic penicillin. (author)

  10. Imaging findings of sternal abnormalities

    International Nuclear Information System (INIS)

    Franquet, T.; Gimenez, A.; Alegret, X.; Sanchis, E.; Rivas, A.

    1997-01-01

    Radiographic findings in the sternal abnormalities are often nonspecific, showing appearances from a localized benign lesion to an aggressive lesion as seen with infections and malignant neoplasms. A specific diagnosis of sternal abnormalities can be suggested on the basis of CT and MR characteristics. Familiarity with the presentation and variable appearance of sternal abnormalities may aid the radiologist is suggesting a specific diagnosis. We present among others characteristic radiographic findings of hemangioma, chondrosarcoma, hydatid disease, and SAPHO syndrome. In those cases in which findings are not specific, cross-sectional imaging modalities may help the clinician in their management. (orig.)

  11. A Global Analysis of Kinase Function in Candida albicans Hyphal Morphogenesis Reveals a Role for the Endocytosis Regulator Akl1

    Directory of Open Access Journals (Sweden)

    Hagit Bar-Yosef

    2018-02-01

    Full Text Available The human pathogenic fungus Candida albicans can switch between yeast and hyphal morphologies as a function of environmental conditions and cellular physiology. The yeast-to-hyphae morphogenetic switch is activated by well-established, kinase-based signal transduction pathways that are induced by extracellular stimuli. In order to identify possible inhibitory pathways of the yeast-to-hyphae transition, we interrogated a collection of C. albicans protein kinases and phosphatases ectopically expressed under the regulation of the TETon promoter. Proportionately more phosphatases than kinases were identified that inhibited hyphal morphogenesis, consistent with the known role of protein phosphorylation in hyphal induction. Among the kinases, we identified AKL1 as a gene that significantly suppressed hyphal morphogenesis in serum. Akl1 specifically affected hyphal elongation rather than initiation: overexpression of AKL1 repressed hyphal growth, and deletion of AKL1 resulted in acceleration of the rate of hyphal elongation. Akl1 suppressed fluid-phase endocytosis, probably via Pan1, a putative clathrin-mediated endocytosis scaffolding protein. In the absence of Akl1, the Pan1 patches were delocalized from the sub-apical region, and fluid-phase endocytosis was intensified. These results underscore the requirement of an active endocytic pathway for hyphal morphogenesis. Furthermore, these results suggest that under standard conditions, endocytosis is rate-limiting for hyphal elongation.

  12. A Global Analysis of Kinase Function in Candida albicans Hyphal Morphogenesis Reveals a Role for the Endocytosis Regulator Akl1.

    Science.gov (United States)

    Bar-Yosef, Hagit; Gildor, Tsvia; Ramírez-Zavala, Bernardo; Schmauch, Christian; Weissman, Ziva; Pinsky, Mariel; Naddaf, Rawi; Morschhäuser, Joachim; Arkowitz, Robert A; Kornitzer, Daniel

    2018-01-01

    The human pathogenic fungus Candida albicans can switch between yeast and hyphal morphologies as a function of environmental conditions and cellular physiology. The yeast-to-hyphae morphogenetic switch is activated by well-established, kinase-based signal transduction pathways that are induced by extracellular stimuli. In order to identify possible inhibitory pathways of the yeast-to-hyphae transition, we interrogated a collection of C. albicans protein kinases and phosphatases ectopically expressed under the regulation of the TETon promoter. Proportionately more phosphatases than kinases were identified that inhibited hyphal morphogenesis, consistent with the known role of protein phosphorylation in hyphal induction. Among the kinases, we identified AKL1 as a gene that significantly suppressed hyphal morphogenesis in serum. Akl1 specifically affected hyphal elongation rather than initiation: overexpression of AKL1 repressed hyphal growth, and deletion of AKL1 resulted in acceleration of the rate of hyphal elongation. Akl1 suppressed fluid-phase endocytosis, probably via Pan1, a putative clathrin-mediated endocytosis scaffolding protein. In the absence of Akl1, the Pan1 patches were delocalized from the sub-apical region, and fluid-phase endocytosis was intensified. These results underscore the requirement of an active endocytic pathway for hyphal morphogenesis. Furthermore, these results suggest that under standard conditions, endocytosis is rate-limiting for hyphal elongation.

  13. MDCT evaluation of sternal variations: Pictorial essay

    International Nuclear Information System (INIS)

    Duraikannu, Chary; Noronha, Olma V; Sundarrajan, Pushparajan

    2016-01-01

    Sternal variations and anomalies have been identified in the past during autopsy or cadaveric studies. Recently, an increasing number of minor sternal variations have been reported with the advent of multidetector computed tomography (CT). Although there are many sternal variations that occur with varying appearance and prevalence, most of them are not recognized or are underreported during routine imaging of thorax. Identification of sternal variations is important to differentiate from pathological conditions and to prevent fatal complications prior to sternal interventions like marrow aspiration or acupuncture. This article aims to describe the minor and asymptomatic sternal variations by multidetector CT and their clinical significance

  14. Regulation of cellulase expression, sporulation, and morphogenesis by velvet family proteins in Trichoderma reesei.

    Science.gov (United States)

    Liu, Kuimei; Dong, Yanmei; Wang, Fangzhong; Jiang, Baojie; Wang, Mingyu; Fang, Xu

    2016-01-01

    Homologs of the velvet protein family are encoded by the ve1, vel2, and vel3 genes in Trichoderma reesei. To test their regulatory functions, the velvet protein-coding genes were disrupted, generating Δve1, Δvel2, and Δvel3 strains. The phenotypic features of these strains were examined to identify their functions in morphogenesis, sporulation, and cellulase expression. The three velvet-deficient strains produced more hyphal branches, indicating that velvet family proteins participate in the morphogenesis in T. reesei. Deletion of ve1 and vel3 did not affect biomass accumulation, while deletion of vel2 led to a significantly hampered growth when cellulose was used as the sole carbon source in the medium. The deletion of either ve1 or vel2 led to the sharp decrease of sporulation as well as a global downregulation of cellulase-coding genes. In contrast, although the expression of cellulase-coding genes of the ∆vel3 strain was downregulated in the dark, their expression in light condition was unaffected. Sporulation was hampered in the ∆vel3 strain. These results suggest that Ve1 and Vel2 play major roles, whereas Vel3 plays a minor role in sporulation, morphogenesis, and cellulase expression.

  15. Sternal wound infection revisited

    International Nuclear Information System (INIS)

    Liberatore, M.; Fiore, V.; D'Agostini, A.; Prosperi, D.; Iurilli, A.P.; Santini, C.; Baiocchi, P.; Galie, M.; Di Nucci, G.D.; Sinatra, R.

    2000-01-01

    Sternal wound infections (SWIs) can be subdivided into two types, superficial or deep, that require different treatments. The clinical diagnosis of superficial SWI is normally easy to perform, whereas the involvement of deep tissues is frequently difficult to detect. Therefore, there is a need for an imaging study that permits the assessment of SWIs and is able to distinguish between superficial and deep SWI. The present work was a prospective study aiming to evaluate the role of technetium-99m hexamethylpropylene amine oxime ( 99m Tc-HMPAO) labelled leucocyte scan in SWI management. Twenty-eight patients with suspected SWIs were included in the study. On the basis of clinical examination they were subdivided into three groups: patients with signs of superficial SWI (group 1), patients with signs of superficial SWI and suspected deep infection (group 2) and patients with suspected deep SWI without superficial involvement (group 3). Ten patients previously submitted to median sternotomy, but without suspected SWI, were also included in the study as a control group (group 4). All patients with suspected SWI had bacteriological examinations of wound secretion, if present. In addition 99m Tc-HMPAO labelled leucocyte scan was performed in all patients. The patients of groups 1, 2 and 3 were treated on the basis of the clinical signs and microbiological findings, independently of the scintigraphic results. The patients of group 4 did not receive treatment. The final assessment of infection was based on histological and microbiological findings or on long-term clinical follow-up. Sensitivity, specificity, accuracy and positive and negative predictive values for scintigraphic and non-scintigraphic results were calculated. In the diagnosis of superficial and deep SWI, clinical and microbiological examination (combined) yielded, respectively, a sensitivity of 68.7% and 100%, a specificity of 77.3% and 80.8%, an accuracy of 73.7% and 86.8%, a positive predictive value of 68

  16. Plexin A3 and turnout regulate motor axonal branch morphogenesis in zebrafish.

    Directory of Open Access Journals (Sweden)

    Rajiv Sainath

    Full Text Available During embryogenesis motor axons navigate to their target muscles, where individual motor axons develop complex branch morphologies. The mechanisms that control axonal branching morphogenesis have been studied intensively, yet it still remains unclear when branches begin to form or how branch locations are determined. Live cell imaging of individual zebrafish motor axons reveals that the first axonal branches are generated at the ventral extent of the myotome via bifurcation of the growth cone. Subsequent branches are generated by collateral branching restricted to their synaptic target field along the distal portion of the axon. This precisely timed and spatially restricted branching process is disrupted in turnout mutants we identified in a forward genetic screen. Molecular genetic mapping positioned the turnout mutation within a 300 kb region encompassing eight annotated genes, however sequence analysis of all eight open reading frames failed to unambiguously identify the turnout mutation. Chimeric analysis and single cell labeling reveal that turnout function is required cell non-autonomously for intraspinal motor axon guidance and peripheral branch formation. turnout mutant motor axons form the first branch on time via growth cone bifurcation, but unlike wild-type they form collateral branches precociously, when the growth cone is still navigating towards the ventral myotome. These precocious collateral branches emerge along the proximal region of the axon shaft typically devoid of branches, and they develop into stable, permanent branches. Furthermore, we find that null mutants of the guidance receptor plexin A3 display identical motor axon branching defects, and time lapse analysis reveals that precocious branch formation in turnout and plexin A3 mutants is due to increased stability of otherwise short-lived axonal protrusions. Thus, plexin A3 dependent intrinsic and turnout dependent extrinsic mechanisms suppress collateral branch

  17. Is sternal rewiring mandatory in surgical treatment of deep sternal wound infections?

    Science.gov (United States)

    Rashed, Aref; Gombocz, Karoly; Alotti, Nasri; Verzar, Zsofia

    2018-04-01

    Deep sternal wound infections (DSWIs) are a rare but serious complication after median sternotomy, and treatment success depends mainly on surgical experience. We compared treatment outcomes after conventional sternal rewiring and reconstruction with no sternal rewiring in patients with a sternal wound infection. We retrospectively enrolled patients who developed a DSWI after an open-heart procedure with median sternotomy at the Department of Cardiac Surgery, at the St. Rafael Hospital, Zalaegerszeg, Hungary, between 2012 and 2016. All patients received negative pressure wound and antibiotic therapy before surgical reconstruction. Patients were divided into groups determined by the reconstruction technique and compared. Subjects were followed up for 12 months, and the primary end-points were readmission and 90-day mortality. Among 3,177 median sternotomy cases, 60 patients developed a DSWI, 4 of whom died of sepsis before surgical treatment. Fifty-six patients underwent surgical reconstruction with conventional sternal rewiring (23 cases, 41%) or another interventions with no sternal refixation (33 cases, 59%). Eighty-one percent of sternal wound infections followed coronary bypass surgery (alone or combinated with another procedures), and 60% were diagnosed after hospital discharge. Staphylococcus aureus was cultured in 30% of all wounds and, 56.5% of cases reconstructed by sternal rewiring vs. 26.5% with no sternal rewiring, (P=0.022). Hospital readmission occurred in 63.6% of the sternal rewiring group vs. 14.7% of the no sternal rewiring group. The rate of death before wound healing or the 90 th postoperative day was 21.7% in the sternal rewiring group vs. 0% in the no sternal rewiring group. The median hospital stay was longer in the sternal rewiring group than in the other group (51 vs. 30 days, P=0.006). Sternal rewiring may be associated with a higher rate of treatment failure than other forms of treatment for sternal wound infections.

  18. Fis1, DLP1, and Pex11p coordinately regulate peroxisome morphogenesis

    International Nuclear Information System (INIS)

    Kobayashi, Shinta; Tanaka, Atsushi; Fujiki, Yukio

    2007-01-01

    Dynamin-like protein 1 (DLP1) and Pex11pβ function in morphogenesis of peroxisomes. In the present work, we investigated whether Fis1 is involved in fission of peroxisomes. Endogenous Fis1 was morphologically detected in peroxisomes as well as mitochondria in wild-type CHO-K1 and DLP1-defective ZP121 cells. Subcellular fractionation studies also revealed the presence of Fis1 in peroxisomes. Peroxisomal Fis1 showed the same topology, i.e., C-tail anchored membrane protein, as the mitochondrial one. Furthermore, ectopic expression of FIS1 induced peroxisome proliferation in CHO-K1 cells, while the interference of FIS1 RNA resulted in tubulation of peroxisomes, hence reducing the number of peroxisomes. Fis1 interacted with Pex11pβ, by direct binding apparently involving the C-terminal region of Pex11pβ in the interaction. Pex11pβ also interacted with each other, whereas the binding of Pex11pβ to DLP1 was not detectable. Moreover, ternary complexes comprising Fis1, Pex11pβ, and DLP1 were detected by chemical cross-linking. We also showed that the highly conserved N-terminal domain of Pex11pβ was required for the homo-oligomerization of Pex11pβ and indispensable for the peroxisome-proliferating activity. Taken together, these findings indicate that Fis1 plays important roles in peroxisome division and maintenance of peroxisome morphology in mammalian cells, possibly in a concerted manner with Pex11pβ and DLP1

  19. The Petunia GRAS Transcription Factor ATA/RAM1 Regulates Symbiotic Gene Expression and Fungal Morphogenesis in Arbuscular Mycorrhiza1

    Science.gov (United States)

    Rich, Mélanie K.

    2015-01-01

    Arbuscular mycorrhiza (AM) is a mutual symbiosis that involves a complex symbiotic interface over which nutrients are exchanged between the plant host and the AM fungus. Dozens of genes in the host are required for the establishment and functioning of the interaction, among them nutrient transporters that mediate the uptake of mineral nutrients delivered by the fungal arbuscules. We have isolated in a genetic mutant screen a petunia (Petunia hybrida) GIBBERELLIC ACID INSENSITIVE, REPRESSOR of GIBBERELLIC ACID INSENSITIVE, and SCARECROW (GRAS)-type transcription factor, ATYPICAL ARBUSCULE (ATA), that acts as the central regulator of AM-related genes and is required for the morphogenesis of arbuscules. Forced mycorrhizal inoculations from neighboring wild-type plants revealed an additional role of ATA in restricting mycorrhizal colonization of the root meristem. The lack of ATA, which represents the ortholog of REQUIRED FOR ARBUSCULAR MYCORRHIZA1 in Medicago truncatula, renders the interaction completely ineffective, hence demonstrating the central role of AM-related genes for arbuscule development and function. PMID:25971550

  20. The Petunia GRAS Transcription Factor ATA/RAM1 Regulates Symbiotic Gene Expression and Fungal Morphogenesis in Arbuscular Mycorrhiza.

    Science.gov (United States)

    Rich, Mélanie K; Schorderet, Martine; Bapaume, Laure; Falquet, Laurent; Morel, Patrice; Vandenbussche, Michiel; Reinhardt, Didier

    2015-07-01

    Arbuscular mycorrhiza (AM) is a mutual symbiosis that involves a complex symbiotic interface over which nutrients are exchanged between the plant host and the AM fungus. Dozens of genes in the host are required for the establishment and functioning of the interaction, among them nutrient transporters that mediate the uptake of mineral nutrients delivered by the fungal arbuscules. We have isolated in a genetic mutant screen a petunia (Petunia hybrida) Gibberellic Acid Insensitive, Repressor of Gibberellic Acid Insensitive, and Scarecrow (GRAS)-type transcription factor, Atypical Arbuscule (ATA), that acts as the central regulator of AM-related genes and is required for the morphogenesis of arbuscules. Forced mycorrhizal inoculations from neighboring wild-type plants revealed an additional role of ATA in restricting mycorrhizal colonization of the root meristem. The lack of ATA, which represents the ortholog of Required For Arbuscular Mycorrhiza1 in Medicago truncatula, renders the interaction completely ineffective, hence demonstrating the central role of AM-related genes for arbuscule development and function. © 2015 American Society of Plant Biologists. All Rights Reserved.

  1. Msx2 Plays a central Role in Regulating Branching Morphogenesis During Mammary Development

    National Research Council Canada - National Science Library

    Liu, Yi-Hsin

    2002-01-01

    The purpose of this study is to determine the role of a transcriptional factor, Msx2, in regulating branching events in the development of the mouse mammary gland To define the function of Msx2 gene...

  2. Sternal reconstruction after post-sternotomy mediastinitis

    Directory of Open Access Journals (Sweden)

    Pankaj Kaul

    2017-11-01

    Full Text Available Abstract Background Deep sternal wound complications are uncommon after cardiac surgery. They comprise sternal dehiscence, deep sternal wound infections and mediastinitis, which will be treated as varying expressions of a singular pathology for reasons explained in the text. Methodology and review This article reviews the definition, prevalence, risk factors, prevention, diagnosis, microbiology and management of deep sternal wound infections and mediastinitis after cardiac surgery. The role of negative pressure wound therapy and initial and delayed surgical management is discussed with special emphasis on plastic techniques with muscle and omental flaps. Recent advances in reconstructive surgery are presented. Conclusions Deep sternal wound complications no longer spell debilitating morbidity and high mortality. Better understanding of risk factors that predispose to deep sternal wound complications and general improvement in theatre protocols for asepsis have dramatically reduced the incidence of deep sternal wound complications. Negative pressure wound therapy and appropriately timed and staged muscle or omental flap reconstruction have transformed the outcomes once these complications occur.

  3. Developmental gene regulation during tomato fruit ripening and in-vitro sepal morphogenesis

    Directory of Open Access Journals (Sweden)

    Ishida Betty K

    2003-08-01

    Full Text Available Abstract Background Red ripe tomatoes are the result of numerous physiological changes controlled by hormonal and developmental signals, causing maturation or differentiation of various fruit tissues simultaneously. These physiological changes affect visual, textural, flavor, and aroma characteristics, making the fruit more appealing to potential consumers for seed dispersal. Developmental regulation of tomato fruit ripening has, until recently, been lacking in rigorous investigation. We previously indicated the presence of up-regulated transcription factors in ripening tomato fruit by data mining in TIGR Tomato Gene Index. In our in-vitro system, green tomato sepals cultured at 16 to 22°C turn red and swell like ripening tomato fruit while those at 28°C remain green. Results Here, we have further examined regulation of putative developmental genes possibly involved in tomato fruit ripening and development. Using molecular biological methods, we have determined the relative abundance of various transcripts of genes during in vitro sepal ripening and in tomato fruit pericarp at three stages of development. A number of transcripts show similar expression in fruits to RIN and PSY1, ripening-associated genes, and others show quite different expression. Conclusions Our investigation has resulted in confirmation of some of our previous database mining results and has revealed differences in gene expression that may be important for tomato cultivar variation. We present new and intriguing information on genes that should now be studied in a more focused fashion.

  4. Regulation of morphogenesis and biocontrol properties in Trichoderma virens by a VELVET protein, Vel1.

    Science.gov (United States)

    Mukherjee, Prasun K; Kenerley, Charles M

    2010-04-01

    Mycoparasitic strains of Trichoderma are applied as commercial biofungicides for control of soilborne plant pathogens. Although the majority of commercial biofungicides are Trichoderma based, chemical pesticides, which are ecological and environmental hazards, still dominate the market. This is because biofungicides are not as effective or consistent as chemical fungicides. Efforts to improve these products have been limited by a lack of understanding of the genetic regulation of biocontrol activities. In this study, using gene knockout and complementation, we identified the VELVET protein Vel1 as a key regulator of biocontrol, as well as morphogenetic traits, in Trichoderma virens, a commercial biocontrol agent. Mutants with mutations in vel1 were defective in secondary metabolism (antibiosis), mycoparasitism, and biocontrol efficacy. In nutrient-rich media they also lacked two types of spores important for survival and development of formulation products: conidia (on agar) and chlamydospores (in liquid shake cultures). These findings provide an opportunity for genetic enhancement of biocontrol and industrial strains of Trichoderma, since Vel1 is very highly conserved across three Trichoderma species.

  5. Disruption of Core Planar Cell Polarity Signaling Regulates Renal Tubule Morphogenesis but Is Not Cystogenic.

    Science.gov (United States)

    Kunimoto, Koshi; Bayly, Roy D; Vladar, Eszter K; Vonderfecht, Tyson; Gallagher, Anna-Rachel; Axelrod, Jeffrey D

    2017-10-23

    Oriented cell division (OCD) and convergent extension (CE) shape developing renal tubules, and their disruption has been associated with polycystic kidney disease (PKD) genes, the majority of which encode proteins that localize to primary cilia. Core planar cell polarity (PCP) signaling controls OCD and CE in other contexts, leading to the hypothesis that disruption of PCP signaling interferes with CE and/or OCD to produce PKD. Nonetheless, the contribution of PCP to tubulogenesis and cystogenesis is uncertain, and two major questions remain unanswered. Specifically, the inference that mutation of PKD genes interferes with PCP signaling is untested, and the importance of PCP signaling for cystogenic PKD phenotypes has not been examined. We show that, during proliferative stages, PCP signaling polarizes renal tubules to control OCD. However, we find that, contrary to the prevailing model, PKD mutations do not disrupt PCP signaling but instead act independently and in parallel with PCP signaling to affect OCD. Indeed, PCP signaling that is normally downregulated once development is completed is retained in cystic adult kidneys. Disrupting PCP signaling results in inaccurate control of tubule diameter, a tightly regulated parameter with important physiological ramifications. However, we show that disruption of PCP signaling is not cystogenic. Our results suggest that regulating tubule diameter is a key function of PCP signaling but that loss of this control does not induce cysts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Endothelium-derived fibronectin regulates neonatal vascular morphogenesis in an autocrine fashion.

    Science.gov (United States)

    Turner, Christopher J; Badu-Nkansah, Kwabena; Hynes, Richard O

    2017-11-01

    Fibronectin containing alternatively spliced EIIIA and EIIIB domains is largely absent from mature quiescent vessels in adults, but is highly expressed around blood vessels during developmental and pathological angiogenesis. The precise functions of fibronectin and its splice variants during developmental angiogenesis however remain unclear due to the presence of cardiac, somitic, mesodermal and neural defects in existing global fibronectin KO mouse models. Using a rare family of surviving EIIIA EIIIB double KO mice, as well as inducible endothelial-specific fibronectin-deficient mutant mice, we show that vascular development in the neonatal retina is regulated in an autocrine manner by endothelium-derived fibronectin, and requires both EIIIA and EIIIB domains and the RGD-binding α5 and αv integrins for its function. Exogenous sources of fibronectin do not fully substitute for the autocrine function of endothelial fibronectin, demonstrating that fibronectins from different sources contribute differentially to specific aspects of angiogenesis.

  7. Kctd10 regulates heart morphogenesis by repressing the transcriptional activity of Tbx5a in zebrafish

    Science.gov (United States)

    Tong, Xiangjun; Zu, Yao; Li, Zengpeng; Li, Wenyuan; Ying, Lingxiao; Yang, Jing; Wang, Xin; He, Shuonan; Liu, Da; Zhu, Zuoyan; Chen, Jianming; Lin, Shuo; Zhang, Bo

    2014-01-01

    The T-box transcription factor Tbx5 (Tbx5a in zebrafish) plays a crucial role in the formation of cardiac chambers in a dose-dependent manner. Its deregulation leads to congenital heart disease. However, little is known regarding its regulation. Here we isolate a zebrafish mutant with heart malformations, called 34c. The affected gene is identified as kctd10, a member of the potassium channel tetramerization domain (KCTD)-containing family. In the mutant, the expressions of the atrioventricular canal marker genes, such as tbx2b, hyaluronan synthase 2 (has2), notch1b and bmp4, are changed. The knockdown of tbx5 rescues the ectopic expression of has2, and knockdown of either tbx5a or has2 alleviates the heart defects. We show that Kctd10 directly binds to Tbx5 to repress its transcriptional activity. Our results reveal a new essential factor for cardiac development and suggest that KCTD10 could be considered as a new causative gene of congenital heart disease.

  8. VPS35 regulates developing mouse hippocampal neuronal morphogenesis by promoting retrograde trafficking of BACE1

    Directory of Open Access Journals (Sweden)

    Chun-Lei Wang

    2012-10-01

    VPS35, a major component of the retromer, plays an important role in the selective endosome-to-Golgi retrieval of membrane proteins. Dysfunction of retromer is a risk factor for neurodegenerative disorders, but its function in developing mouse brain remains poorly understood. Here we provide evidence for VPS35 promoting dendritic growth and maturation, and axonal protein transport in developing mouse hippocampal neurons. Embryonic hippocampal CA1 neurons suppressing Vps35 expression by in utero electroporation of its micro RNAs displayed shortened apical dendrites, reduced dendritic spines, and swollen commissural axons in the neonatal stage, those deficits reflecting a defective protein transport/trafficking in developing mouse neurons. Further mechanistic studies showed that Vps35 depletion in neurons resulted in an impaired retrograde trafficking of BACE1 (β1-secretase and altered BACE1 distribution. Suppression of BACE1 expression in CA1 neurons partially rescued both dendritic and axonal deficits induced by Vps35-deficiency. These results thus demonstrate that BACE1 acts as a critical cargo of retromer in vitro and in vivo, and suggest that VPS35 plays an essential role in regulating apical dendritic maturation and in preventing axonal spheroid formation in developing hippocampal neurons.

  9. Klf8 regulates left-right asymmetric patterning through modulation of Kupffer's vesicle morphogenesis and spaw expression.

    Science.gov (United States)

    Lin, Che-Yi; Tsai, Ming-Yuan; Liu, Yu-Hsiu; Lu, Yu-Fen; Chen, Yi-Chung; Lai, Yun-Ren; Liao, Hsin-Chi; Lien, Huang-Wei; Yang, Chung-Hsiang; Huang, Chang-Jen; Hwang, Sheng-Ping L

    2017-07-17

    . Interestingly, klf8 mutant embryos, generated by a CRISPR-Cas9 system, showed bilateral spaw expression in the LPM at late somite stages. This observation may be partly attributed to compensatory upregulation of klf12b, because klf12b knockdown reduced the percentage of klf8 mutants exhibiting bilateral spaw expression. Our results demonstrate that zebrafish Klf8 regulates left-right asymmetric patterning by modulating both Kupffer's vesicle morphogenesis and spaw expression in the left LPM.

  10. MRI findings of prolonged post-traumatic sternal pain

    International Nuclear Information System (INIS)

    Grosse, Alexandra; Grosse, Claudia; Anderson, Suzanne; Steinbach, Lynne

    2007-01-01

    The objective of this study was to characterize the different causes of prolonged sternal pain following thoracic trauma with involvement of the sternum and to define criteria for sternal nonunion diagnosis using MRI. Five patients with abnormalities of the sternum were evaluated for prolonged sternal pain following thoracic trauma using MRI. MR images were evaluated by two radiologists in consensus. The patients were selected from the radiology database, which included 8 patients with post-traumatic prolonged sternal pain. Two patients (n = 2) revealed a sternal nonunion after sternal fracture. One patient had a sternal fracture with delayed union and minor displacement of the sternal halves. Abnormal signal intensity alterations adjacent to and within the manubrio-sternal joint were evident in 2 patients and considered due to trauma-related changes in the manubrio-sternal joint. The 3 patients who were not included in the study had no abnormalities of the sternum: 1 of them proved to have a well-healed sternal fracture and nonunion of a rib fracture, 1 had subtle Tietze's syndrome, and 1 patient revealed no pathological findings on imaging. Various factors may be responsible for prolonged sternal pain following thoracic trauma, and these can be viewed with MRI. In cases of sternal nonunion there was common fluid-like signal in the fracture interspace between the bony edges, and the bone marrow adjacent to the nonunion showed altered signal intensity. MRI identified sternal nonunion and other trauma-related abnormalities of the sternum following chest trauma. (orig.)

  11. Sternal plate fixation for sternal wound reconstruction: initial experience (Retrospective study

    Directory of Open Access Journals (Sweden)

    Musgrave Melinda

    2011-04-01

    Full Text Available Abstract Background Median sternotomy infection and bony nonunion are two commonly described complications which occur in 0.4 - 5.1% of cardiac procedures. Although relatively infrequent, these complications can lead to significant morbidity and mortality. The aim of this retrospective study is to evaluate the initial experience of a transverse plate fixation system following wound complications associated with sternal dehiscence with or without infection following cardiac surgery. Methods A retrospective chart review of 40 consecutive patients who required sternal wound reconstruction post sternotomy was performed. Soft tissue debridement with removal of all compromised tissue was performed. Sternal debridement was carried using ronguers to healthy bleeding bone. All patients underwent sternal fixation using three rib plates combined with a single manubrial plate (Titanium Sternal Fixation System®, Synthes. Incisions were closed in a layered fashion with the pectoral muscles being advanced to the midline. Data were expressed as mean ± SD, Median (range or number (%. Statistical analyses were made by using Excel 2003 for Windows (Microsoft, Redmond, WA, USA. Results There were 40 consecutive patients, 31 males and 9 females. Twenty two patients (55% were diagnosed with sternal dehiscence alone and 18 patients (45% with associated wound discharge. Thirty eight patients went on to heal their wounds. Two patients developed recurrent wound infection and required VAC therapy. Both were immunocompromised. Median post-op ICU stay was one day with the median hospital stay of 18 days after plating. Conclusion Sternal plating appears to be an effective option for the treatment of sternal wound dehiscence associated with sternal instability. Long-term follow-up and further larger studies are needed to address the indications, benefits and complications of sternal plating.

  12. Regulation of neurite morphogenesis by interaction between R7 regulator of G protein signaling complexes and G protein subunit Gα13.

    Science.gov (United States)

    Scherer, Stephanie L; Cain, Matthew D; Kanai, Stanley M; Kaltenbronn, Kevin M; Blumer, Kendall J

    2017-06-16

    The R7 regulator of G protein signaling family (R7-RGS) critically regulates nervous system development and function. Mice lacking all R7-RGS subtypes exhibit diverse neurological phenotypes, and humans bearing mutations in the retinal R7-RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms heterotrimeric complexes with Gβ 5 and R7-RGS-binding protein (R7BP) that regulate G protein-coupled receptor signaling by accelerating deactivation of G i/o α-subunits, several neurological phenotypes of R7-RGS knock-out mice are not readily explained by dysregulated G i/o signaling. Accordingly, we used tandem affinity purification and LC-MS/MS to search for novel proteins that interact with R7-RGS heterotrimers in the mouse brain. Among several proteins detected, we focused on Gα 13 because it had not been linked to R7-RGS complexes before. Split-luciferase complementation assays indicated that Gα 13 in its active or inactive state interacts with R7-RGS heterotrimers containing any R7-RGS isoform. LARG (leukemia-associated Rho guanine nucleotide exchange factor (GEF)), PDZ-RhoGEF, and p115RhoGEF augmented interaction between activated Gα 13 and R7-RGS heterotrimers, indicating that these effector RhoGEFs can engage Gα 13 ·R7-RGS complexes. Because Gα 13 /R7-RGS interaction required R7BP, we analyzed phenotypes of neuronal cell lines expressing RGS7 and Gβ 5 with or without R7BP. We found that neurite retraction evoked by Gα 12/13 -dependent lysophosphatidic acid receptors was augmented in R7BP-expressing cells. R7BP expression blunted neurite formation evoked by serum starvation by signaling mechanisms involving Gα 12/13 but not Gα i/o These findings provide the first evidence that R7-RGS heterotrimers interact with Gα 13 to augment signaling pathways that regulate neurite morphogenesis. This mechanism expands the diversity of functions whereby R7-RGS complexes regulate critical aspects of nervous system development and function. © 2017 by

  13. Autoimmune Myasthenia Gravis after Sternal Fracture

    Directory of Open Access Journals (Sweden)

    Jens A. Petersen

    2012-01-01

    Full Text Available We report a 54-year-old woman who suffered a commotio cerebri, whiplash injury and a chest trauma with sternal fracture due to a high-velocity car accident. Two months later, she developed unilateral ptosis and blurred vision, which worsened during the day. Multiple diagnoses were suggested, ranging from thoracic outlet syndrome towards depression. Symptoms persisted and five years later, the patient consulted a neurologist. Laboratory analysis revealed significantly elevated levels of antibodies to acetylcholine receptors, and the diagnosis of myasthenia gravis was made. Speculatively, the damage of retrosternal thymic remnants due to a sternal fracture might have precipitated the condition or exacerbated subclinical disease.

  14. Evolution and functional significance of derived sternal ossification patterns in ornithothoracine birds

    Science.gov (United States)

    O’connor, J. K.; Zheng, X.-T.; Sullivan, C.; Chuong, C.-M.; Wang, X.-L.; Li, A.; Wang, Y.; Zhang, X.-M.; Zhou, Z.-H.

    2017-01-01

    The midline pattern of sternal ossification characteristic of the Cretaceous enantiornithine birds is unique among the Ornithodira, the group containing birds, nonavian dinosaurs and pterosaurs. This has been suggested to indicate that Enantiornithes is not the sister group of Ornithuromorpha, the clade that includes living birds and their close relatives, which would imply rampant convergence in many nonsternal features between enantiornithines and ornithuromorphs. However, detailed comparisons reveal greater similarity between neornithine (i.e. crown group bird) and enantiornithine modes of sternal ossification than previously recognized. Furthermore, a new subadult enantiornithine specimen demonstrates that sternal ossification followed a more typically ornithodiran pattern in basal members of the clade. This new specimen, referable to the Pengornithidae, indicates that the unique ossification pattern observed in other juvenile enantiornithines is derived within Enantiornithes. A similar but clearly distinct pattern appears to have evolved in parallel in the ornithuromorph lineage. The atypical mode of sternal ossification in some derived enantiornithines should be regarded as an autapomorphic condition rather than an indication that enantiornithines are not close relatives of ornithuromorphs. Based on what is known about molecular mechanisms for morphogenesis and the possible selective advantages, the parallel shifts to midline ossification that took place in derived enantiornithines and living neognathous birds appear to have been related to the development of a large ventral keel, which is only present in ornithuromorphs and enantiornithines. Midline ossification can serve to medially reinforce the sternum at a relatively early ontogenetic stage, which would have been especially beneficial during the protracted development of the superprecocial Cretaceous enantiornithines. PMID:26079847

  15. DEAR1 is a dominant regulator of acinar morphogenesis and an independent predictor of local recurrence-free survival in early-onset breast cancer.

    Directory of Open Access Journals (Sweden)

    Steven T Lott

    2009-05-01

    Full Text Available Breast cancer in young women tends to have a natural history of aggressive disease for which rates of recurrence are higher than in breast cancers detected later in life. Little is known about the genetic pathways that underlie early-onset breast cancer. Here we report the discovery of DEAR1 (ductal epithelium-associated RING Chromosome 1, a novel gene encoding a member of the TRIM (tripartite motif subfamily of RING finger proteins, and provide evidence for its role as a dominant regulator of acinar morphogenesis in the mammary gland and as an independent predictor of local recurrence-free survival in early-onset breast cancer.Suppression subtractive hybridization identified DEAR1 as a novel gene mapping to a region of high-frequency loss of heterozygosity (LOH in a number of histologically diverse human cancers within Chromosome 1p35.1. In the breast epithelium, DEAR1 expression is limited to the ductal and glandular epithelium and is down-regulated in transition to ductal carcinoma in situ (DCIS, an early histologic stage in breast tumorigenesis. DEAR1 missense mutations and homozygous deletion (HD were discovered in breast cancer cell lines and tumor samples. Introduction of the DEAR1 wild type and not the missense mutant alleles to complement a mutation in a breast cancer cell line, derived from a 36-year-old female with invasive breast cancer, initiated acinar morphogenesis in three-dimensional (3D basement membrane culture and restored tissue architecture reminiscent of normal acinar structures in the mammary gland in vivo. Stable knockdown of DEAR1 in immortalized human mammary epithelial cells (HMECs recapitulated the growth in 3D culture of breast cancer cell lines containing mutated DEAR1, in that shDEAR1 clones demonstrated disruption of tissue architecture, loss of apical basal polarity, diffuse apoptosis, and failure of lumen formation. Furthermore, immunohistochemical staining of a tissue microarray from a cohort of 123 young

  16. MRI findings of prolonged post-traumatic sternal pain

    Energy Technology Data Exchange (ETDEWEB)

    Grosse, Alexandra; Grosse, Claudia; Anderson, Suzanne [University Hospital of Berne, Department of Diagnostic, Pediatric and Interventional Radiology, Berne (Switzerland); Steinbach, Lynne [University of California San Francisco, Department of Radiology, San Francisco, CA (United States)

    2007-05-15

    The objective of this study was to characterize the different causes of prolonged sternal pain following thoracic trauma with involvement of the sternum and to define criteria for sternal nonunion diagnosis using MRI. Five patients with abnormalities of the sternum were evaluated for prolonged sternal pain following thoracic trauma using MRI. MR images were evaluated by two radiologists in consensus. The patients were selected from the radiology database, which included 8 patients with post-traumatic prolonged sternal pain. Two patients (n = 2) revealed a sternal nonunion after sternal fracture. One patient had a sternal fracture with delayed union and minor displacement of the sternal halves. Abnormal signal intensity alterations adjacent to and within the manubrio-sternal joint were evident in 2 patients and considered due to trauma-related changes in the manubrio-sternal joint. The 3 patients who were not included in the study had no abnormalities of the sternum: 1 of them proved to have a well-healed sternal fracture and nonunion of a rib fracture, 1 had subtle Tietze's syndrome, and 1 patient revealed no pathological findings on imaging. Various factors may be responsible for prolonged sternal pain following thoracic trauma, and these can be viewed with MRI. In cases of sternal nonunion there was common fluid-like signal in the fracture interspace between the bony edges, and the bone marrow adjacent to the nonunion showed altered signal intensity. MRI identified sternal nonunion and other trauma-related abnormalities of the sternum following chest trauma. (orig.)

  17. Regulation of root morphogenesis in arbuscular mycorrhizae: what role do fungal exudates, phosphate, sugars and hormones play in lateral root formation?

    Science.gov (United States)

    Fusconi, Anna

    2014-01-01

    Background Arbuscular mycorrhizae (AMs) form a widespread root–fungus symbiosis that improves plant phosphate (Pi) acquisition and modifies the physiology and development of host plants. Increased branching is recognized as a general feature of AM roots, and has been interpreted as a means of increasing suitable sites for colonization. Fungal exudates, which are involved in the dialogue between AM fungi and their host during the pre-colonization phase, play a well-documented role in lateral root (LR) formation. In addition, the increased Pi content of AM plants, in relation to Pi-starved controls, as well as changes in the delivery of carbohydrates to the roots and modulation of phytohormone concentration, transport and sensitivity, are probably involved in increasing root system branching. Scope This review discusses the possible causes of increased branching in AM plants. The differential root responses to Pi, sugars and hormones of potential AM host species are also highlighted and discussed in comparison with those of the non-host Arabidopsis thaliana. Conclusions Fungal exudates are probably the main compounds regulating AM root morphogenesis during the first colonization steps, while a complex network of interactions governs root development in established AMs. Colonization and high Pi act synergistically to increase root branching, and sugar transport towards the arbusculated cells may contribute to LR formation. In addition, AM colonization and high Pi generally increase auxin and cytokinin and decrease ethylene and strigolactone levels. With the exception of cytokinins, which seem to regulate mainly the root:shoot biomass ratio, these hormones play a leading role in governing root morphogenesis, with strigolactones and ethylene blocking LR formation in the non-colonized, Pi-starved plants, and auxin inducing them in colonized plants, or in plants grown under high Pi conditions. PMID:24227446

  18. The safe zone for blinded sternal interventions based on CT evaluation of midline congenital sternal foramina

    International Nuclear Information System (INIS)

    Boruah, Deb K.; Dhingani, Dhaval D.; Achar, Shashidhar; Augustine, Antony; Mahanta, Kangkana; Prakash, Arjun; Yadav, Rajnikant R.

    2016-01-01

    The aim of this study was to evaluate the safe zone for performing blind sternal procedures based on computed tomography (CT) evaluation of congenital midline sternal foramina using multidetector computed tomography (MDCT). This retrospective study was carried out on 1,180 patients who underwent MDCT of the thorax from March 2015 to February 2016. The MDCT images were evaluated in axial and reformatted planes. Morphometry and prevalence of midline congenital sternal foramina (SF) and manubrio-foraminal distance (MFD) were evaluated. The safe zone was defined for a blinded intervention, based on palpable anatomical landmarks. Data were presented in terms of percentage, mean ± standard deviation and calculations were carried out using Microsoft Excel. The prevalence of SF in our study sample was 11.6 %. The majority of SF were located in a typical position in the lower sternal body at the level of fifth costo-chondral junction (CCJ) in 108 patients (78.8 %). The structure directly beneath the SF was mediastinal fat in 73 patients (53.3 %), followed by anterior pericardium in 44 patients (32.1 %) and lung parenchyma in 20 patients (14.6 %). The mean MFD in our study population was 11.90 ± 1.31 cm. Sternal interventions should be avoided at the level of fourth to sixth CCJ, which is considered the danger zone. An intervention at the fourth to sixth CCJ may lead to disastrous consequences in patients who have SF. (orig.)

  19. The safe zone for blinded sternal interventions based on CT evaluation of midline congenital sternal foramina

    Energy Technology Data Exchange (ETDEWEB)

    Boruah, Deb K.; Dhingani, Dhaval D.; Achar, Shashidhar; Augustine, Antony; Mahanta, Kangkana [Assam Medical College and Hospital, Department of Radio-diagnosis, Dibrugarh, Assam (India); Prakash, Arjun [NIMHANS, Department of Radio-diagnosis, Bangalore, Karnataka (India); Yadav, Rajnikant R. [Sanjay Gandhi Post Graduate Institute and Medical Sciences, Department of Radio-diagnosis, Lucknow (India)

    2016-12-15

    The aim of this study was to evaluate the safe zone for performing blind sternal procedures based on computed tomography (CT) evaluation of congenital midline sternal foramina using multidetector computed tomography (MDCT). This retrospective study was carried out on 1,180 patients who underwent MDCT of the thorax from March 2015 to February 2016. The MDCT images were evaluated in axial and reformatted planes. Morphometry and prevalence of midline congenital sternal foramina (SF) and manubrio-foraminal distance (MFD) were evaluated. The safe zone was defined for a blinded intervention, based on palpable anatomical landmarks. Data were presented in terms of percentage, mean ± standard deviation and calculations were carried out using Microsoft Excel. The prevalence of SF in our study sample was 11.6 %. The majority of SF were located in a typical position in the lower sternal body at the level of fifth costo-chondral junction (CCJ) in 108 patients (78.8 %). The structure directly beneath the SF was mediastinal fat in 73 patients (53.3 %), followed by anterior pericardium in 44 patients (32.1 %) and lung parenchyma in 20 patients (14.6 %). The mean MFD in our study population was 11.90 ± 1.31 cm. Sternal interventions should be avoided at the level of fourth to sixth CCJ, which is considered the danger zone. An intervention at the fourth to sixth CCJ may lead to disastrous consequences in patients who have SF. (orig.)

  20. The regulation of tooth morphogenesis is associated with epithelial cell proliferation and the expression of Sonic hedgehog through epithelial-mesenchymal interactions

    International Nuclear Information System (INIS)

    Ishida, Kentaro; Murofushi, Mayumi; Nakao, Kazuhisa; Morita, Ritsuko; Ogawa, Miho; Tsuji, Takashi

    2011-01-01

    Research highlights: → Bioengineered teeth regulated the contact area of epithelium and mesenchyme. → The crown width is regulated by the contact area of the epithelium and mesenchyme. → This regulation is associated with cell proliferation and Sonic hedgehog expression. → The cusp number is correlated with the crown width of the bioengineered tooth. → Cell proliferation and Shh expression areas regulate the tooth morphogenesis. -- Abstract: Ectodermal organs, such as the tooth, salivary gland, hair, and mammary gland, develop through reciprocal epithelial-mesenchymal interactions. Tooth morphologies are defined by the crown width and tooth length (macro-morphologies), and by the number and locations of the cusp and roots (micro-morphologies). In our current study, we report that the crown width of a bioengineered molar tooth, which was reconstructed using dissociated epithelial and mesenchymal cells via an organ germ method, can be regulated by the contact area between epithelial and mesenchymal cell layers. We further show that this is associated with cell proliferation and Sonic hedgehog (Shh) expression in the inner enamel epithelium after the germ stage has formed a secondary enamel knot. We also demonstrate that the cusp number is significantly correlated with the crown width of the bioengineered tooth. These findings suggest that the tooth micro-morphology, i.e. the cusp formation, is regulated after the tooth width, or macro-morphology, is determined. These findings also suggest that the spatiotemporal patterning of cell proliferation and the Shh expression areas in the epithelium regulate the crown width and cusp formation of the developing tooth.

  1. Regulation of cell wall morphogenesis in Bacillus subtilis by recruitment of PBP1 to the MreB helix.

    Science.gov (United States)

    Kawai, Yoshikazu; Daniel, Richard A; Errington, Jeffery

    2009-03-01

    The bacterial actin homologue MreB plays a key role in cell morphogenesis. In Bacillus subtilis MreB is essential under normal growth conditions and mreB mutants are defective in the control of cell diameter. However, the precise role of MreB is still unclear. Analysis of the lethal phenotypic consequences of mreB disruption revealed an unusual bulging phenotype that precedes cell death. A similar phenotype was seen in wild-type cells at very low Mg(2+) concentrations. We found that inactivation of the major bi-functional penicillin-binding protein (PBP) PBP1 of B. subtilis restored the viability of an mreB null mutant as well as preventing bulging in both mutant and wild-type backgrounds. Bulging was associated with delocalization of PBP1. We show that the normal pattern of localization of PBP1 is dependent on MreB and that the proteins can physically interact using in vivo pull-down and bacterial two-hybrid approaches. Interactions between MreB and several other PBPs were also detected. Our results suggest that MreB filaments associate directly with the peptidoglycan biosynthetic machinery in B. subtilis as part of the mechanism that brings about controlled cell elongation.

  2. Prx1 and Prx2 cooperatively regulate the morphogenesis of the medial region of the mandibular process

    Science.gov (United States)

    Balic, Anamaria; Adams, Douglas; Mina, Mina

    2009-01-01

    Mice lacking both Prx1 and Prx2 display severe abnormalities in the mandible. Our analysis showed that complete loss of Prx gene products leads to growth abnormalities in the mandibular processes evident as early as E10.5 associated with changes in the survival of the mesenchyme in the medial region. Changes in the gene expression in the medial and lateral regions were related to gradual loss of a subpopulation of mesenchyme in the medial region expressing eHand. Our analysis also showed that Prx gene products are required for the initiation and maintenance of chondrogenesis and terminal differentiation of the chondrocytes in the caudal and rostral ends of Meckel’s cartilage. The fusion of the mandibular processes in the Prx1/Prx2 double mutants is caused by accelerated ossification. These observations together show that during mandibular morphogenesis Prx gene products play multiple roles including the cell survival, the region-specific terminal differentiation of Meckelian chondrocytes and osteogenesis. PMID:19777594

  3. A versatile overexpression strategy in the pathogenic yeast Candida albicans: identification of regulators of morphogenesis and fitness.

    Directory of Open Access Journals (Sweden)

    Murielle Chauvel

    Full Text Available Candida albicans is the most frequently encountered human fungal pathogen, causing both superficial infections and life-threatening systemic diseases. Functional genomic studies performed in this organism have mainly used knock-out mutants and extensive collections of overexpression mutants are still lacking. Here, we report the development of a first generation C. albicans ORFeome, the improvement of overexpression systems and the construction of two new libraries of C. albicans strains overexpressing genes for components of signaling networks, in particular protein kinases, protein phosphatases and transcription factors. As a proof of concept, we screened these collections for genes whose overexpression impacts morphogenesis or growth rates in C. albicans. Our screens identified genes previously described for their role in these biological processes, demonstrating the functionality of our strategy, as well as genes that have not been previously associated to these processes. This article emphasizes the potential of systematic overexpression strategies to improve our knowledge of regulatory networks in C. albicans. The C. albicans plasmid and strain collections described here are available at the Fungal Genetics Stock Center. Their extension to a genome-wide scale will represent important resources for the C. albicans community.

  4. Inner-membrane proteins PMI/TMEM11 regulate mitochondrial morphogenesis independently of the DRP1/MFN fission/fusion pathways.

    Science.gov (United States)

    Rival, Thomas; Macchi, Marc; Arnauné-Pelloquin, Laetitia; Poidevin, Mickael; Maillet, Frédéric; Richard, Fabrice; Fatmi, Ahmed; Belenguer, Pascale; Royet, Julien

    2011-03-01

    Mitochondria are highly dynamic organelles that can change in number and morphology during cell cycle, development or in response to extracellular stimuli. These morphological dynamics are controlled by a tight balance between two antagonistic pathways that promote fusion and fission. Genetic approaches have identified a cohort of conserved proteins that form the core of mitochondrial remodelling machineries. Mitofusins (MFNs) and OPA1 proteins are dynamin-related GTPases that are required for outer- and inner-mitochondrial membrane fusion respectively whereas dynamin-related protein 1 (DRP1) is the master regulator of mitochondrial fission. We demonstrate here that the Drosophila PMI gene and its human orthologue TMEM11 encode mitochondrial inner-membrane proteins that regulate mitochondrial morphogenesis. PMI-mutant cells contain a highly condensed mitochondrial network, suggesting that PMI has either a pro-fission or an anti-fusion function. Surprisingly, however, epistatic experiments indicate that PMI shapes the mitochondria through a mechanism that is independent of drp1 and mfn. This shows that mitochondrial networks can be shaped in higher eukaryotes by at least two separate pathways: one PMI-dependent and one DRP1/MFN-dependent.

  5. The canonical Wnt signaling activator, R-spondin2, regulates craniofacial patterning and morphogenesis within the branchial arch through ectodermal-mesenchymal interaction

    Science.gov (United States)

    Jin, Yong-Ri; Turcotte, Taryn J.; Crocker, Alison L.; Han, Xiang Hua; Yoon, Jeong Kyo

    2011-01-01

    R-spondins are a recently characterized family of secreted proteins that activate Wnt/β-catenin signaling. Herein, we determine R-spondin2 (Rspo2) function in craniofacial development in mice. Mice lacking a functional Rspo2 gene exhibit craniofacial abnormalities such as mandibular hypoplasia, maxillary and mandibular skeletal deformation, and cleft palate. We found that loss of the mouse Rspo2 gene significantly disrupted Wnt/β-catenin signaling and gene expression within the first branchial arch (BA1). Rspo2, which is normally expressed in BA1 mesenchymal cells, regulates gene expression through a unique ectoderm-mesenchyme interaction loop. The Rspo2 protein, potentially in combination with ectoderm-derived Wnt ligands, up-regulates Msx1 and Msx2 expression within mesenchymal cells. In contrast, Rspo2 regulates expression of the Dlx5, Dlx6, and Hand2 genes in mesenchymal cells via inducing expression of their upstream activator, Endothelin1 (Edn1), within ectodermal cells. Loss of Rspo2 also causes increased cell apoptosis, especially within the aboral (or caudal) domain of the BA1, resulting in hypoplasia of the BA1. Severely reduced expression of Fgf8, a survival factor for mesenchymal cells, in the ectoderm of Rspo2−/− embryos is likely responsible for increased cell apoptosis. Additionally, we found that cleft palate in Rspo2−/− mice is not associated with defects intrinsic to the palatal shelves. A possible cause of cleft palate is a delay of proper palatal shelf elevation that may result from the small mandible and a failure of lowering the tongue. Thus, our study identifies Rspo2 as a mesenchyme-derived factor that plays critical roles in regulating BA1 patterning and morphogenesis through ectodermal-mesenchymal interaction and a novel genetic factor for cleft palate. PMID:21237142

  6. Sternal tuberculosis | Sachdeva | Annals of Medical and Health ...

    African Journals Online (AJOL)

    Extra‑pulmonary tuberculosis constitutes 15‑20% of total tuberculosis (TB) case load in immuno‑competent patients. Affliction of the skeletal system is rare with still rarer presentation of sternal osteomyelitis even in endemic countries. A patient with primary sternal TB presenting with multiple cutaneous sinuses over the ...

  7. A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis

    DEFF Research Database (Denmark)

    Siegel, Gabriele; Obernosterer, Gregor; Fiore, Roberto

    2009-01-01

    of acyl protein thioesterase 1 (APT1), an enzyme regulating the palmitoylation status of proteins that are known to function at the synapse, including the alpha(13) subunits of G proteins (Galpha(13)). RNA-interference-mediated knockdown of APT1 and the expression of membrane-localized Galpha(13) both...... suppress spine enlargement caused by inhibition of miR-138, suggesting that APT1-regulated depalmitoylation of Galpha(13) might be an important downstream event of miR-138 function. Our results uncover a previously unknown miRNA-dependent mechanism in neurons and demonstrate a previously unrecognized...

  8. Two novel transcriptional regulators are essential for infection-related morphogenesis and pathogenicity of the rice blast fungus Magnaporthe oryzae.

    Directory of Open Access Journals (Sweden)

    Xia Yan

    2011-12-01

    Full Text Available The cyclic AMP-dependent protein kinase A signaling pathway plays a major role in regulating plant infection by the rice blast fungus Magnaporthe oryzae. Here, we report the identification of two novel genes, MoSOM1 and MoCDTF1, which were discovered in an insertional mutagenesis screen for non-pathogenic mutants of M. oryzae. MoSOM1 or MoCDTF1 are both necessary for development of spores and appressoria by M. oryzae and play roles in cell wall differentiation, regulating melanin pigmentation and cell surface hydrophobicity during spore formation. MoSom1 strongly interacts with MoStu1 (Mstu1, an APSES transcription factor protein, and with MoCdtf1, while also interacting more weakly with the catalytic subunit of protein kinase A (CpkA in yeast two hybrid assays. Furthermore, the expression levels of MoSOM1 and MoCDTF1 were significantly reduced in both Δmac1 and ΔcpkA mutants, consistent with regulation by the cAMP/PKA signaling pathway. MoSom1-GFP and MoCdtf1-GFP fusion proteins localized to the nucleus of fungal cells. Site-directed mutagenesis confirmed that nuclear localization signal sequences in MoSom1 and MoCdtf1 are essential for their sub-cellular localization and biological functions. Transcriptional profiling revealed major changes in gene expression associated with loss of MoSOM1 during infection-related development. We conclude that MoSom1 and MoCdtf1 functions downstream of the cAMP/PKA signaling pathway and are novel transcriptional regulators associated with cellular differentiation during plant infection by the rice blast fungus.

  9. The tailless ortholog nhr-67 regulates patterning of gene expression and morphogenesis in the C. elegans vulva.

    Directory of Open Access Journals (Sweden)

    Jolene S Fernandes

    2007-04-01

    Full Text Available Regulation of spatio-temporal gene expression in diverse cell and tissue types is a critical aspect of development. Progression through Caenorhabditis elegans vulval development leads to the generation of seven distinct vulval cell types (vulA, vulB1, vulB2, vulC, vulD, vulE, and vulF, each with its own unique gene expression profile. The mechanisms that establish the precise spatial patterning of these mature cell types are largely unknown. Dissection of the gene regulatory networks involved in vulval patterning and differentiation would help us understand how cells generate a spatially defined pattern of cell fates during organogenesis. We disrupted the activity of 508 transcription factors via RNAi and assayed the expression of ceh-2, a marker for vulB fate during the L4 stage. From this screen, we identified the tailless ortholog nhr-67 as a novel regulator of gene expression in multiple vulval cell types. We find that one way in which nhr-67 maintains cell identity is by restricting inappropriate cell fusion events in specific vulval cells, namely vulE and vulF. nhr-67 exhibits a dynamic expression pattern in the vulval cells and interacts with three other transcriptional regulators cog-1 (Nkx6.1/6.2, lin-11 (LIM, and egl-38 (Pax2/5/8 to generate the composite expression patterns of their downstream targets. We provide evidence that egl-38 regulates gene expression in vulB1, vulC, vulD, vulE, as well as vulF cells. We demonstrate that the pairwise interactions between these regulatory genes are complex and vary among the seven cell types. We also discovered a striking regulatory circuit that affects a subset of the vulval lineages: cog-1 and nhr-67 inhibit both one another and themselves. We postulate that the differential levels and combinatorial patterns of lin-11, cog-1, and nhr-67 expression are a part of a regulatory code for the mature vulval cell types.

  10. The use of antigibberelins with different mechanisms of action on morphogenesis and production process regulation in the plant Solanum melongena (Solanaceae

    Directory of Open Access Journals (Sweden)

    V. G. Kuriata

    2016-03-01

    Full Text Available The influence of antigibberelin on the growth, development and productivity of eggplant was investigated. It was established that the use of tebuconazole and chlormequat chloride is a highly effective tool for regulation of morphogenesis and productivity of eggplant. We found that retardants slowed the growth of plants, and increased the number of leaves and leaf area and dry substance weight of the whole plant. Under the influence of Esfon ethylene producers the inhibition of the growth process was not accompanied by increase of the number, weight and area of leaves.Antigibberelin agents caused the thickening of chlorenchyma and the growth of the columnar cells and cell sizes of spongy parenchyma. Under the action of agents the thickness of the upper and lower epidermis of the leaf increased. As a result of mesostructural and morphometric changes of leaf structure under the influence of retardants the leaf index and specific leaf surface density increased.The growth inhibitory agents increased the chlorophyll content in leaves and caused the growth of chlorophyll index in crops.Retardants reduced the content of sugar and starch in leaves because of their enhanced outflow to fruits, the amount of which was predicted to be greater. Under the influence of Esfon the flow of carbohydrates to the acceptor areas was slower.The use of retardants of triazole and onium origin positively influenced the formation of productivity elements of the culture, which led to increase in the fruit yield. The use of tebuconazole was found to be the most effective.

  11. Regulation of Morphogenesis and Biocontrol Properties in Trichoderma virens by a VELVET Protein, Vel1▿ †

    Science.gov (United States)

    Mukherjee, Prasun K.; Kenerley, Charles M.

    2010-01-01

    Mycoparasitic strains of Trichoderma are applied as commercial biofungicides for control of soilborne plant pathogens. Although the majority of commercial biofungicides are Trichoderma based, chemical pesticides, which are ecological and environmental hazards, still dominate the market. This is because biofungicides are not as effective or consistent as chemical fungicides. Efforts to improve these products have been limited by a lack of understanding of the genetic regulation of biocontrol activities. In this study, using gene knockout and complementation, we identified the VELVET protein Vel1 as a key regulator of biocontrol, as well as morphogenetic traits, in Trichoderma virens, a commercial biocontrol agent. Mutants with mutations in vel1 were defective in secondary metabolism (antibiosis), mycoparasitism, and biocontrol efficacy. In nutrient-rich media they also lacked two types of spores important for survival and development of formulation products: conidia (on agar) and chlamydospores (in liquid shake cultures). These findings provide an opportunity for genetic enhancement of biocontrol and industrial strains of Trichoderma, since Vel1 is very highly conserved across three Trichoderma species. PMID:20154111

  12. Wnt ligands from the embryonic surface ectoderm regulate ‘bimetallic strip’ optic cup morphogenesis in mouse

    Science.gov (United States)

    Carpenter, April C.; Smith, April N.; Wagner, Heidi; Cohen-Tayar, Yamit; Rao, Sujata; Wallace, Valerie; Ashery-Padan, Ruth; Lang, Richard A.

    2015-01-01

    The Wnt/β-catenin response pathway is central to many developmental processes. Here, we assessed the role of Wnt signaling in early eye development using the mouse as a model system. We showed that the surface ectoderm region that includes the lens placode expressed 12 out of 19 possible Wnt ligands. When these activities were suppressed by conditional deletion of wntless (Le-cre; Wlsfl/fl) there were dramatic consequences that included a saucer-shaped optic cup, ventral coloboma, and a deficiency of periocular mesenchyme. This phenotype shared features with that produced when the Wnt/β-catenin pathway co-receptor Lrp6 is mutated or when retinoic acid (RA) signaling in the eye is compromised. Consistent with this, microarray and cell fate marker analysis identified a series of expression changes in genes known to be regulated by RA or by the Wnt/β-catenin pathway. Using pathway reporters, we showed that Wnt ligands from the surface ectoderm directly or indirectly elicit a Wnt/β-catenin response in retinal pigment epithelium (RPE) progenitors near the optic cup rim. In Le-cre; Wlsfl/fl mice, the numbers of RPE cells are reduced and this can explain, using the principle of the bimetallic strip, the curvature of the optic cup. These data thus establish a novel hypothesis to explain how differential cell numbers in a bilayered epithelium can lead to shape change. PMID:25715397

  13. N,N-dimethyl hexadecylamine and related amines regulate root morphogenesis via jasmonic acid signaling in Arabidopsis thaliana.

    Science.gov (United States)

    Raya-González, Javier; Velázquez-Becerra, Crisanto; Barrera-Ortiz, Salvador; López-Bucio, José; Valencia-Cantero, Eduardo

    2017-05-01

    Plant growth-promoting rhizobacteria are natural inhabitants of roots, colonize diverse monocot and dicot species, and affect several functional traits such as root architecture, adaptation to adverse environments, and protect plants from pathogens. N,N-dimethyl-hexadecylamine (C16-DMA) is a rhizobacterial amino lipid that modulates the postembryonic development of several plants, likely as part of volatile blends. In this work, we evaluated the bioactivity of C16-DMA and other related N,N-dimethyl-amines with varied length and found that inhibition of primary root growth was related to the length of the acyl chain. C16-DMA inhibited primary root growth affecting cell division and elongation, while promoting lateral root formation and root hair growth and density in Arabidopsis thaliana (Arabidopsis) wild-type (WT) seedlings. Interestingly, C16-DMA induced the expression of the jasmonic acid (JA)-responsive gene marker pLOX2:uidA, while JA-related mutants jar1, coi1-1, and myc2 affected on JA biosynthesis and perception, respectively, are compromised in C16-DMA responses. Comparison of auxin-regulated gene expression, root architectural changes in WT, and auxin-related mutants aux1-7, tir1/afb2/afb3, and arf7-1/arf19-1 to C16-DMA shows that the C16-DMA effects occur independently of auxin signaling. Together, these results reveal a novel class of aminolipids modulating root organogenesis via crosstalk with the JA signaling pathway.

  14. Interaction of E-cadherin and PTEN regulates morphogenesis and growth arrest in human mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Fournier, Marcia V.; Fata, Jimmie E.; Martin, Katherine J.; Yaswen, Paul; Bissell, Mina J.

    2009-06-03

    PTEN is a dual function phosphatase with tumor suppressor function compromised in a wide spectrum of cancers. Because tissue polarity and architecture are crucial modulators of normal and malignant behavior, we postulated that PTEN may play a role in maintenance of tissue integrity. We used two non-malignant human mammary epithelial cell lines (HMECs) that form polarized, growth-arrested structures (acini) when cultured in 3-dimensional laminin-rich extracellular matrix gels (3D lrECM). As acini begin to form, PTEN accumulates in both the cytoplasm, and at cell-cell contacts where it colocalizes with E-cadherin/{beta}-catenin complex. Reduction of PTEN levels by shRNA in lrECM prevents formation of organized breast acini and disrupts growth arrest. Importantly, disruption of acinar polarity and cell-cell contact by E-cadherin function-blocking antibodies reduces endogenous PTEN protein levels and inhibits its accumulation at cell-cell contacts. Conversely, in SKBR3 breast cancer cells lacking endogenous E-cadherin expression, exogenous introduction of E-cadherin gene causes induction of PTEN expression and its accumulation at sites of cell interactions. These studies provide evidence that E-cadherin regulates both the PTEN protein levels and its recruitment to cell-cell junctions in 3D lrECM indicating a dynamic reciprocity between architectural integrity and the levels and localization of PTEN. This interaction thus appears to be a critical integrator of proliferative and morphogenetic signaling in breast epithelial cells.

  15. Premature sternal fusion in gonadal dysgenesis with coarctation

    International Nuclear Information System (INIS)

    Herman, T.E.; Kushner, D.C.; Cleveland, R.H.

    1985-01-01

    In reviewing lateral chest roentgenograms in three infants with Turner's syndrome and aortic coarctation, and in infant with mixed gonadal dysgenesis and aortic coarctation, we have found obvious sternal fusion abnormalities which are reported here. (orig./MG)

  16. Sternal fractures as a manifestation of abusive injury in children

    International Nuclear Information System (INIS)

    Hechter, Sloane; Manson, David; Huyer, Dirk

    2002-01-01

    Sternal fractures are rare injuries in children. The rarity of this injury is likely due to both the relative plasticity of the pediatric thorax and to the difficulty in establishing a radiographic diagnosis without dedicated views. Current literature suggests that this injury in young children is highly specific for abusive injury.Hypothesis. Sternal fractures are not highly specific for abusive injury. Materials and methods. This was a retrospective radiographic and clinical chart review of all documented sternal fractures over an 11-year period at a large pediatric hospital.Results. Of 12 children with sternal fractures identified, four were ≤2 years of age and eight were ≥3 years of age. The mechanism of injury was suspicious for child abuse in two children. Both of these children were ≤2 years of age. In one toddler, an unwitnessed injury resulted in extensive initial familial anxiety until abusive injury was excluded.Conclusion. Sternal fractures are unusual injuries, yet they, in themselves, are not highly specific for abusive injury. (orig.)

  17. Sternal fractures as a manifestation of abusive injury in children

    Energy Technology Data Exchange (ETDEWEB)

    Hechter, Sloane; Manson, David [Department of Diagnostic Imaging, Hospital for Sick Children, 555 University Ave, Toronto, Ontario, M5G 1X8 (Canada); Huyer, Dirk [Department of Pediatrics, Division of Suspected Child Abuse and Neglect, Hospital for Sick Children, Toronto, Ontario (Canada)

    2002-12-01

    Sternal fractures are rare injuries in children. The rarity of this injury is likely due to both the relative plasticity of the pediatric thorax and to the difficulty in establishing a radiographic diagnosis without dedicated views. Current literature suggests that this injury in young children is highly specific for abusive injury.Hypothesis. Sternal fractures are not highly specific for abusive injury. Materials and methods. This was a retrospective radiographic and clinical chart review of all documented sternal fractures over an 11-year period at a large pediatric hospital.Results. Of 12 children with sternal fractures identified, four were {<=}2 years of age and eight were {>=}3 years of age. The mechanism of injury was suspicious for child abuse in two children. Both of these children were {<=}2 years of age. In one toddler, an unwitnessed injury resulted in extensive initial familial anxiety until abusive injury was excluded.Conclusion. Sternal fractures are unusual injuries, yet they, in themselves, are not highly specific for abusive injury. (orig.)

  18. Ascidian notochord morphogenesis

    OpenAIRE

    Jiang, Di; Smith, William C.

    2007-01-01

    The development of the notochord involves a complex set of cellular behaviors. While these morphogenic behaviors are common to all chordates, the ascidian provides a particularly attractive experimental model because of its relative simplicity. In particular, all notochord morphogenesis in ascidians takes place with only 40 cells, as opposed to the hundreds of cells in vertebrate models systems. Initial steps in ascidian notochord development convert a monolayer of epithelial-like cells in th...

  19. Feedback, Lineages and Self-Organizing Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Sameeran Kunche

    2016-03-01

    Full Text Available Feedback regulation of cell lineage progression plays an important role in tissue size homeostasis, but whether such feedback also plays an important role in tissue morphogenesis has yet to be explored. Here we use mathematical modeling to show that a particular feedback architecture in which both positive and negative diffusible signals act on stem and/or progenitor cells leads to the appearance of bistable or bi-modal growth behaviors, ultrasensitivity to external growth cues, local growth-driven budding, self-sustaining elongation, and the triggering of self-organization in the form of lamellar fingers. Such behaviors arise not through regulation of cell cycle speeds, but through the control of stem or progenitor self-renewal. Even though the spatial patterns that arise in this setting are the result of interactions between diffusible factors with antagonistic effects, morphogenesis is not the consequence of Turing-type instabilities.

  20. Feedback, Lineages and Self-Organizing Morphogenesis

    Science.gov (United States)

    Calof, Anne L.; Lowengrub, John S.; Lander, Arthur D.

    2016-01-01

    Feedback regulation of cell lineage progression plays an important role in tissue size homeostasis, but whether such feedback also plays an important role in tissue morphogenesis has yet to be explored. Here we use mathematical modeling to show that a particular feedback architecture in which both positive and negative diffusible signals act on stem and/or progenitor cells leads to the appearance of bistable or bi-modal growth behaviors, ultrasensitivity to external growth cues, local growth-driven budding, self-sustaining elongation, and the triggering of self-organization in the form of lamellar fingers. Such behaviors arise not through regulation of cell cycle speeds, but through the control of stem or progenitor self-renewal. Even though the spatial patterns that arise in this setting are the result of interactions between diffusible factors with antagonistic effects, morphogenesis is not the consequence of Turing-type instabilities. PMID:26989903

  1. Sea Urchin Morphogenesis.

    Science.gov (United States)

    McClay, David R

    2016-01-01

    In the sea urchin morphogenesis follows extensive molecular specification. The specification controls the many morphogenetic events and these, in turn, precede patterning steps that establish the larval body plan. To understand how the embryo is built it was necessary to understand those series of molecular steps. Here an example of the historical sequence of those discoveries is presented as it unfolded over the last 50 years, the years during which major progress in understanding development of many animals and plants was documented by CTDB. In sea urchin development a rich series of experimental studies first established many of the phenomenological components of skeletal morphogenesis and patterning without knowledge of the molecular components. The many discoveries of transcription factors, signals, and structural proteins that contribute to the shape of the endoskeleton of the sea urchin larva then followed as molecular tools became available. A number of transcription factors and signals were discovered that were necessary for specification, morphogenesis, and patterning. Perturbation of the transcription factors and signals provided the means for assembling models of the gene regulatory networks used for specification and controlled the subsequent morphogenetic events. The earlier experimental information informed perturbation experiments that asked how patterning worked. As a consequence it was learned that ectoderm provides a series of patterning signals to the skeletogenic cells and as a consequence the skeletogenic cells secrete a highly patterned skeleton based on their ability to genotypically decode the localized reception of several signals. We still do not understand the complexity of the signals received by the skeletogenic cells, nor do we understand in detail how the genotypic information shapes the secreted skeletal biomineral, but the current knowledge at least outlines the sequence of events and provides a useful template for future

  2. Sternal instability measured with radiostereometric analysis. A study of method feasibility, accuracy and precision

    DEFF Research Database (Denmark)

    Vestergaard, Rikke Falsig; Søballe, Kjeld; Hasenkam, John Michael

    2018-01-01

    BACKGROUND: A small, but unstable, saw-gap may hinder bone-bridging and induce development of painful sternal dehiscence. We propose the use of Radiostereometric Analysis (RSA) for evaluation of sternal instability and present a method validation. METHODS: Four bone analogs (phantoms) were sterno...... modality feasible for clinical evaluation of sternal stability in research. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02738437 , retrospectively registered.......BACKGROUND: A small, but unstable, saw-gap may hinder bone-bridging and induce development of painful sternal dehiscence. We propose the use of Radiostereometric Analysis (RSA) for evaluation of sternal instability and present a method validation. METHODS: Four bone analogs (phantoms) were...

  3. The usefulness of sagittal reformation for diagnosis of sternal fracture

    Energy Technology Data Exchange (ETDEWEB)

    Im, Dong Jin; Hahn, Seok; Kim, Young Ju [Dept. of Radiology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)

    2014-01-15

    The purpose of our study was to evaluate the usefulness of sagittal reformation of chest computed tomography for the diagnosis of sternal fracture after trauma. We retrospectively reviewed medical records and chest computer tomography (CT) of 716 patients in the emergency department after trauma between January and December 2010. Two radiologists investigated chest CT images. We investigated numbers and locations of sternal fractures on axial images only and on both axial and sagittal images for each radiologist. First, radiologist found sternal fractures in 58 patients (70.7%) on only axial images, and 80 (97.5%) on both axial and sagittal images. Second, radiologist found fractures in 67 patients (81.7%) on axial image only and 81 (98.7%) on both axial and sagittal images. The sensitivity increased after adding sagittal reformation images for each radiologist (p < 0.05, respectively). On the axial images, the interobserver agreement was low (k 0.596) between the two radiologists. However, on both axial and sagittal images, the interobserver agreement increased (k = 0.872). Sagittal reformation of chest CT increases the chance of diagnosis for sternal fracture and leads to early diagnosis resulting in appropriate treatment.

  4. The usefulness of sagittal reformation for diagnosis of sternal fracture

    International Nuclear Information System (INIS)

    Im, Dong Jin; Hahn, Seok; Kim, Young Ju

    2014-01-01

    The purpose of our study was to evaluate the usefulness of sagittal reformation of chest computed tomography for the diagnosis of sternal fracture after trauma. We retrospectively reviewed medical records and chest computer tomography (CT) of 716 patients in the emergency department after trauma between January and December 2010. Two radiologists investigated chest CT images. We investigated numbers and locations of sternal fractures on axial images only and on both axial and sagittal images for each radiologist. First, radiologist found sternal fractures in 58 patients (70.7%) on only axial images, and 80 (97.5%) on both axial and sagittal images. Second, radiologist found fractures in 67 patients (81.7%) on axial image only and 81 (98.7%) on both axial and sagittal images. The sensitivity increased after adding sagittal reformation images for each radiologist (p < 0.05, respectively). On the axial images, the interobserver agreement was low (k 0.596) between the two radiologists. However, on both axial and sagittal images, the interobserver agreement increased (k = 0.872). Sagittal reformation of chest CT increases the chance of diagnosis for sternal fracture and leads to early diagnosis resulting in appropriate treatment.

  5. The laparoscopically harvested omental flap for deep sternal wound infection

    NARCIS (Netherlands)

    van Wingerden, Jan J.; Coret, Matijn E. H.; van Nieuwenhoven, Christianne A.; Totté, Eric R.

    2010-01-01

    To report our experience with the laparoscopically harvested omental flap in the treatment of deep sternal wound infection, and to present a modification and introduce two supportive techniques in the perioperative management. Between June 2005 and September 2007, six patients with grade IV (El

  6. Improved results of the vacuum assisted closure and Nitinol clips sternal closure after postoperative deep sternal wound infection.

    Science.gov (United States)

    Tocco, Maria Pia; Costantino, Alberto; Ballardini, Milva; D'Andrea, Claudio; Masala, Marcello; Merico, Eusebio; Mosillo, Luigi; Sordini, Paolo

    2009-05-01

    Postoperative deep sternal wound infection is a severe complication of cardiac surgery, with a high mortality rate and a high morbidity rate. The objective of this prospective study is to report our experience with the vacuum assisted closure (VAC) system for the management of deep wound infection. We also devised an innovative closure technique post VAC therapy using thermo reactive clips. The advantage of this technique is that the posterior face of the sternum does not have to be separated from the mediastinal structures thus minimising the risk of damage. From October 2006 to October 2008, we prospectively evaluated 21 patients affected by mediastinitis after sternotomy. Nineteen patients had sternotomy for coronary artery bypass grafting (CABG), one patient for aortic valve replacement (AVR) and another one for ascending aortic replacement (AAR). All patients were treated with the VAC system at the time of infection diagnosis. When the wound tissue appeared viable and the microbiological cultures were negative, the chest was closed using the most suitable procedure for the patient in question; nine patients were closed using pectoralis flaps, nine patients using Nitinol clips, one patient with a combined technique (use of Nitinol clips and muscle flap), one patient with a direct wound closure and another patient, who needed AAR with a homograft performed in another institution, was closed using sternal wires. We had no mortality; wound healing was successfully achieved in all patients. In more than 50% of the patients, the VAC therapy allowed direct sternal resynthesis. The average duration of the vacuum therapy was 26 days (range 14-37 days). VAC is a safe and effective option in the treatment of post-sternotomy mediastinitis, with excellent survival and immediate improvement of local wound conditions; furthermore, the use of Nitinol clips after VAC therapy demonstrated to be a safe and non-invasive option for sternal resynthesis. After VAC therapy, a

  7. Failure analysis of the fractured wires in sternal perichronal loops.

    Science.gov (United States)

    Chao, Jesús; Voces, Roberto; Peña, Carmen

    2011-10-01

    We report failure analysis of sternal wires in two cases in which a perichronal fixation technique was used to close the sternotomy. Various characteristics of the retrieved wires were compared to those of unused wires of the same grade and same manufacturer and with surgical wire specifications. In both cases, wire fracture was un-branched and transgranular and proceeded by a high cycle fatigue process, apparently in the absence of corrosion. However, stress anlysis indicates that the effective stress produced during strong coughing is lower than the yield strength. Our findings suggest that in order to reduce the risk for sternal dehiscence, the diameter of the wire used should be increased. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Sex estimation from sternal measurements using multidetector computed tomography.

    Science.gov (United States)

    Ekizoglu, Oguzhan; Hocaoglu, Elif; Inci, Ercan; Bilgili, Mustafa Gokhan; Solmaz, Dilek; Erdil, Irem; Can, Ismail Ozgur

    2014-12-01

    We aimed to show the utility and reliability of sternal morphometric analysis for sex estimation.Sex estimation is a very important step in forensic identification. Skeletal surveys are main methods for sex estimation studies. Morphometric analysis of sternum may provide high accuracy rated data in sex discrimination. In this study, morphometric analysis of sternum was evaluated in 1 mm chest computed tomography scans for sex estimation. Four hundred forty 3 subjects (202 female, 241 male, mean age: 44 ± 8.1 [distribution: 30-60 year old]) were included the study. Manubrium length (ML), mesosternum length (2L), Sternebra 1 (S1W), and Sternebra 3 (S3W) width were measured and also sternal index (SI) was calculated. Differences between genders were evaluated by student t-test. Predictive factors of sex were determined by discrimination analysis and receiver operating characteristic (ROC) analysis. Male sternal measurement values are significantly higher than females (P discrimination analysis, MSL has high accuracy rate with 80.2% in females and 80.9% in males. MSL also has the best sensitivity (75.9%) and specificity (87.6%) values. Accuracy rates were above 80% in 3 stepwise discrimination analysis for both sexes. Stepwise 1 (ML, MSL, S1W, S3W) has the highest accuracy rate in stepwise discrimination analysis with 86.1% in females and 83.8% in males. Our study showed that morphometric computed tomography analysis of sternum might provide important information for sex estimation.

  9. Surgical repair of a congenital sternal cleft in a cat.

    Science.gov (United States)

    Schwarzkopf, Ilona; Bavegems, Valerie C A; Vandekerckhove, Peter M F P; Melis, Sanne M; Cornillie, Pieter; de Rooster, Hilde

    2014-07-01

    To describe the clinical findings, diagnosis, and treatment of an incomplete cleft of the 5th-8th sternebra and a cranioventral abdominal wall hernia in a 2 month old Ragdoll kitten and to evaluate the short- and long-term outcome. Clinical report. Ragdoll cat (n = 1), 2 months old. Sternal cleft was confirmed by thoracic radiographs. Computed tomography (CT) was used to plan an optimal surgical approach. A ventral median incision was made, starting at the 3rd sternebra and extended into the abdomen. Ostectomy of the proximal part of the 5th left sternebra was performed. Lateral periosteal flaps were created, unfolded, and absorbable monofilament sutures preplaced to facilitate closure and the repair was reinforced by 2 peristernal sutures. A bone graft was applied, and the free margin of the omentum was sutured to the cranial aspect of the wound. No major complications occurred. At 3 weeks, CT scan confirmed approximation of the hemisternebrae and at 10 months, complete fusion of the hemisternebrae had not occurred, but a strong connection of the sternal bars was present. Sternal cleft is a rare congenital abnormality that can be corrected surgically with favorable outcome. © Copyright 2014 by The American College of Veterinary Surgeons.

  10. Isolated sternal fracture - a swing-related injury in two children

    International Nuclear Information System (INIS)

    DeFriend, D.E.; Franklin, K.

    2001-01-01

    Isolated fracture of the sternum is an uncommon injury in a child. We report two cases of sternal fracture following falls from swings, which illustrate the mechanisms of injury in sternal fracture. One fracture resulted from a flexion compression injury of the thoracic spine, which has very rarely been reported in children. Sternal fracture should be considered in the differential diagnosis of acute chest pain in a child where there has been an activity involving hyperflexion force. (orig.)

  11. The morphogenesis of feathers.

    Science.gov (United States)

    Yu, Mingke; Wu, Ping; Widelitz, Randall B; Chuong, Cheng-Ming

    2002-11-21

    Feathers are highly ordered, hierarchical branched structures that confer birds with the ability of flight. Discoveries of fossilized dinosaurs in China bearing 'feather-like' structures have prompted interest in the origin and evolution of feathers. However, there is uncertainty about whether the irregularly branched integumentary fibres on dinosaurs such as Sinornithosaurus are truly feathers, and whether an integumentary appendage with a major central shaft and notched edges is a non-avian feather or a proto-feather. Here, we use a developmental approach to analyse molecular mechanisms in feather-branching morphogenesis. We have used the replication-competent avian sarcoma retrovirus to deliver exogenous genes to regenerating flight feather follicles of chickens. We show that the antagonistic balance between noggin and bone morphogenetic protein 4 (BMP4) has a critical role in feather branching, with BMP4 promoting rachis formation and barb fusion, and noggin enhancing rachis and barb branching. Furthermore, we show that sonic hedgehog (Shh) is essential for inducing apoptosis of the marginal plate epithelia, which results in spaces between barbs. Our analyses identify the molecular pathways underlying the topological transformation of feathers from cylindrical epithelia to the hierarchical branched structures, and provide insights on the possible developmental mechanisms in the evolution of feather forms.

  12. Preliminary experience with a new device for delayed sternal closure strategy in cardiac surgery.

    Science.gov (United States)

    Santini, Francesco; Onorati, Francesco; Telesca, Mariassunta; Faggian, Giuseppe; Mazzucco, Alessandro

    2012-06-01

    Open chest management with delayed sternal closure (DSC) is a valuable strategy in the management of patients with postcardiotomy hemodynamic instability or severe coagulopathy. The conventional extemporized material available for off-label sternal stenting however may limit its efficacy. We evaluated outcomes of patients with refractory severe postcardiotomy cardiogenic shock (SPCCS) treated with DSC using a novel temporary sternal spreader (NTSS) which allows myocardial recovery by progressive controlled approximation of the sternal edges. Seven patients (4 male, mean age 66.5 ± 5 years) with refractory SPCCS showing acute hemodynamic instability at sternal closure, were implanted with the NTSS, consisting of stainless-steel branches linked to 2 diverging plates of polyether-ether ketone, whose progressive opening/closing mechanism can be controlled from outside the chest with a rotating steel wire. The sternal wound was closed by an elastic membrane to achieve a sterile field. Swan-Ganz monitoring was employed, and clinical outcomes evaluated. The device was successfully implanted in all patients without device-related complications or failures. Progressive approximation of sternal edges, titrated on cardiac index values, was successfully completed allowing subsequent uneventful sternal closure in all. Mean time from SPCCS to sternal closure was 70 ± 21 hours. No patient developed infective complications or late hemodynamic instability after device removal and sternal closure. One patient (14%) died of multiorgan failure on postoperative day 9. Despite the limited number of patients enrolled, the NTSS proved safe and effective in allowing complete myocardial recovery after SPCCS, avoiding hemodynamic instability related to abrupt sternal closure, with no occurrence of infective complications.

  13. Perithecium morphogenesis in Sordaria macrospora.

    Science.gov (United States)

    Lord, Kathryn M; Read, Nick D

    2011-04-01

    The perithecium of the self-fertile ascomycete Sordaria macrospora provides an excellent model in which to analyse fungal multicellular development. This study provides a detailed analysis of perithecium morphogenesis in the wild type and eight developmental mutants of S. macrospora, using a range of correlative microscopical techniques. Fundamentally, perithecia and other complex multicellular structures produced by fungi arise by hyphal aggregation and adhesion, and these processes are followed by specialization and septation of hyphal compartments within the aggregates. Perithecial morphogenesis can be divided into the ascogonial, protoperithecial, and perithecial stages of development. At least 13 specialized, morphologically distinct cell-types are involved in perithecium morphogenesis, and these fall into three basic classes: hyphae, conglutinate cells and spores. Conglutinate cells arise from hyphal adhesion and certain perithecial hyphae develop from conglutinate cells. Various hypha-conglutinate cell transitions play important roles during the development of the perithecial wall and neck. Copyright © 2010. Published by Elsevier Inc.

  14. Treatment of sternal wound infection with vacuum-assisted closure.

    Science.gov (United States)

    Dezfuli, Bobby; Li, Chin-Shang; Young, J Nilas; Wong, Michael S

    2013-02-01

    Previous work has demonstrated the efficacy of vacuum-assisted closure (VAC) in the treatment of poststernotomy local wound infections, compared to historical treatment protocol. The negative pressure has been found to protect wounds against contamination, prevent wound fluid retention, increase blood flow, and increase rates of granulation tissue formation. For this study, a retrospective analysis compared patients receiving VAC as definitive treatment versus bridging to delayed flap closure. Sixteen patients developed sternal wound infections after cardiac surgeries at the authors' institution from 2006 to 2008. Data was gathered regarding patient comorbidities, treatment method, and outcome. Study objectives included assessment of risk factors that warranted secondary surgicalclosure and examination of long-term followup where VAC was thedefinitive treatment modality. Group A (n = 12) had VAC as the final treatment modality. Group B (n = 4) required myocutaneous flap closure. One patient in Group B passed away prior to flap surgery. Both groups had similar risk factors, except Group B had a higher risk of body mass index (BMI) > 35 that was near statistically significant (P = 0.085; odds ratio = 0.0, 95% CI = [0.0 - 1.21]). Group A required a shorter hospital stay on average. Long-term follow-up showed the majority of Group A had completely healed sternal wounds 2-3 years from initial cardiac surgery. Vacuum-assisted closure as definitive treatment modality is a successful, first line therapy for local superficial sternal wound infections. When deep infections occur, however, VAC as bridge-to-flap coverage is recommended over attempted secondary healing with VAC. .

  15. Staphylococcus aureus sternal osteomyelitis: a rare cause of chest pain

    Directory of Open Access Journals (Sweden)

    Kaur M

    2015-10-01

    Full Text Available Chest pain is a common presenting symptom with a broad differential. Life-threatening cardiac and pulmonary etiologies of chest pain should be evaluated first. However, it is critical to perform a thorough assessment for other sources of chest pain in order to limit morbidity and mortality from less common causes. We present a rare case of a previously healthy 45 year old man who presented with focal, substernal, reproducible chest pain and Staphylococcus aureus bacteremia who was later found to have primary Staphylococcus aureus sternal osteomyelitis.

  16. Pseudomass of the sternal manubrium in osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Yekeler, Ensar; Kumbasar, Basak; Dursun, Memduh; Tunaci, Mehtap [Department of Radiology, Istanbul University, Istanbul Faculty of Medicine, 34390, Capa, Istanbul (Turkey); Cantez, Serdar; Emiroglu, Halil Haldun [Department of Pediatrics, Istanbul University, Istanbul Faculty of Medicine, 34390, Capa, Istanbul (Turkey)

    2003-06-01

    Skeletal abnormalities such as hypertrophic callus formation and ''popcorn'' calcifications are rare radiological findings of osteogenesis imperfecta, causing tumor-like appearances on imaging. We report on a 7-year-old girl with osteogenesis imperfecta presenting with hepatomegaly and palpable lymphadenopathy in the left inguinal region on physical examination. Computed tomography examination revealed a high-density mass-like lesion of the manubrium sterni. Ultrasonography and a lateral roentgenogram of the chest verified that this was a pseudomass caused by a bowed sternal manubrium. (orig.)

  17. Pseudomass of the sternal manubrium in osteogenesis imperfecta

    International Nuclear Information System (INIS)

    Yekeler, Ensar; Kumbasar, Basak; Dursun, Memduh; Tunaci, Mehtap; Cantez, Serdar; Emiroglu, Halil Haldun

    2003-01-01

    Skeletal abnormalities such as hypertrophic callus formation and ''popcorn'' calcifications are rare radiological findings of osteogenesis imperfecta, causing tumor-like appearances on imaging. We report on a 7-year-old girl with osteogenesis imperfecta presenting with hepatomegaly and palpable lymphadenopathy in the left inguinal region on physical examination. Computed tomography examination revealed a high-density mass-like lesion of the manubrium sterni. Ultrasonography and a lateral roentgenogram of the chest verified that this was a pseudomass caused by a bowed sternal manubrium. (orig.)

  18. Investigation of Sternal Photoplethysmography – Design of a Vital Sign Patch

    DEFF Research Database (Denmark)

    Chreiteh, Shadi

    %). In the second study, sternal PPG recording was conducted from 30 admitted patients with either asthma or Chronic Obstructive Pulmonary Disease (COPD). We compared the SpO2 levels simultaneously obtained from the sternal PPG recording and a conventional finger pulse oximeter. The Pearson correlation between...... to 36 breaths/min the Pearson correlation was 0.93 (p

  19. Epithelial morphogenesis: the mouse eye as a model system.

    Science.gov (United States)

    Chauhan, Bharesh; Plageman, Timothy; Lou, Ming; Lang, Richard

    2015-01-01

    Morphogenesis is the developmental process by which tissues and organs acquire the shape that is critical to their function. Here, we review recent advances in our understanding of the mechanisms that drive morphogenesis in the developing eye. These investigations have shown that regulation of the actin cytoskeleton is central to shaping the presumptive lens and retinal epithelia that are the major components of the eye. Regulation of the actin cytoskeleton is mediated by Rho family GTPases, by signaling pathways and indirectly, by transcription factors that govern the expression of critical genes. Changes in the actin cytoskeleton can shape cells through the generation of filopodia (that, in the eye, connect adjacent epithelia) or through apical constriction, a process that produces a wedge-shaped cell. We have also learned that one tissue can influence the shape of an adjacent one, probably by direct force transmission, in a process we term inductive morphogenesis. Though these mechanisms of morphogenesis have been identified using the eye as a model system, they are likely to apply broadly where epithelia influence the shape of organs during development. © 2015 Elsevier Inc. All rights reserved.

  20. RhoJ is an endothelial cell-restricted Rho GTPase that mediates vascular morphogenesis and is regulated by the transcription factor ERG

    NARCIS (Netherlands)

    Yuan, Lei; Sacharidou, Anastasia; Stratman, Amber N.; Le Bras, Alexandra; Zwiers, Peter J.; Spokes, Katherine; Bhasin, Manoj; Shih, Shou-ching; Nagy, Janice A.; Molema, Grietje; Aird, William C.; Davis, George E.; Oettgen, Peter

    2011-01-01

    ERG is a member of the ETS transcription factor family that is highly enriched in endothelial cells (ECs). To further define the role of ERG in regulating EC function, we evaluated the effect of ERG knockdown on EC lumen formation in 3D collagen matrices. Blockade of ERG using siRNA completely

  1. Lace plant ethylene receptors, AmERS1a and AmERS1c, regulate ethylene-induced programmed cell death during leaf morphogenesis.

    Science.gov (United States)

    Rantong, Gaolathe; Evans, Rodger; Gunawardena, Arunika H L A N

    2015-10-01

    The lace plant, Aponogeton madagascariensis, is an aquatic monocot that forms perforations in its leaves as part of normal leaf development. Perforation formation occurs through developmentally regulated programmed cell death (PCD). The molecular basis of PCD regulation in the lace plant is unknown, however ethylene has been shown to play a significant role. In this study, we examined the role of ethylene receptors during perforation formation. We isolated three lace plant ethylene receptors AmERS1a, AmERS1b and AmERS1c. Using quantitative PCR, we examined their transcript levels at seven stages of leaf development. Through laser-capture microscopy, transcript levels were also determined in cells undergoing PCD and cells not undergoing PCD (NPCD cells). AmERS1a transcript levels were significantly lower in window stage leaves (in which perforation formation and PCD are occurring) as compared to all other leaf developmental stages. AmERS1a and AmERS1c (the most abundant among the three receptors) had the highest transcript levels in mature stage leaves, where PCD is not occurring. Their transcript levels decreased significantly during senescence-associated PCD. AmERS1c had significantly higher transcript levels in NPCD compared to PCD cells. Despite being significantly low in window stage leaves, AmERS1a transcripts were not differentially expressed between PCD and NPCD cells. The results suggested that ethylene receptors negatively regulate ethylene-controlled PCD in the lace plant. A combination of ethylene and receptor levels determines cell fate during perforation formation and leaf senescence. A new model for ethylene emission and receptor expression during lace plant perforation formation and senescence is proposed.

  2. The LacI–Family Transcription Factor, RbsR, Is a Pleiotropic Regulator of Motility, Virulence, Siderophore and Antibiotic Production, Gas Vesicle Morphogenesis and Flotation in Serratia

    Directory of Open Access Journals (Sweden)

    Chin M. Lee

    2017-09-01

    Full Text Available Gas vesicles (GVs are proteinaceous, gas-filled organelles used by some bacteria to enable upward movement into favorable air/liquid interfaces in aquatic environments. Serratia sp. ATCC39006 (S39006 was the first enterobacterium discovered to produce GVs naturally. The regulation of GV assembly in this host is complex and part of a wider regulatory network affecting various phenotypes, including antibiotic biosynthesis. To identify new regulators of GVs, a comprehensive mutant library containing 71,000 insertion mutants was generated by random transposon mutagenesis and 311 putative GV-defective mutants identified. Three of these mutants were found to have a transposon inserted in a LacI family transcription regulator gene (rbsR of the putative ribose operon. Each of these rbsR mutants was GV-defective; no GVs were visible by phase contrast microscopy (PCM or transmission electron microscopy (TEM. GV deficiency was caused by the reduction of gvpA1 and gvrA transcription (the first genes of the two contiguous operons in the GV gene locus. Our results also showed that a mutation in rbsR was highly pleiotropic; the production of two secondary metabolites (carbapenem and prodigiosin antibiotics was abolished. Interestingly, the intrinsic resistance to the carbapenem antibiotic was not affected by the rbsR mutation. In addition, the production of a siderophore, cellulase and plant virulence was reduced in the mutant, whereas it exhibited increased swimming and swarming motility. The RbsR protein was predicted to bind to regions upstream of at least 18 genes in S39006 including rbsD (the first gene of the ribose operon and gvrA. Electrophoretic mobility shift assays (EMSA confirmed that RbsR bound to DNA sequences upstream of rbsD, but not gvrA. The results of this study indicate that RbsR is a global regulator that affects the modulation of GV biogenesis, but also with complex pleiotropic physiological impacts in S39006.

  3. Expression and functional role of sprouty-2 in breast morphogenesis.

    Science.gov (United States)

    Sigurdsson, Valgardur; Ingthorsson, Saevar; Hilmarsdottir, Bylgja; Gustafsdottir, Sigrun M; Franzdottir, Sigridur Rut; Arason, Ari Jon; Steingrimsson, Eirikur; Magnusson, Magnus K; Gudjonsson, Thorarinn

    2013-01-01

    Branching morphogenesis is a mechanism used by many species for organogenesis and tissue maintenance. Receptor tyrosine kinases (RTKs), including epidermal growth factor receptor (EGFR) and the sprouty protein family are believed to be critical regulators of branching morphogenesis. The aim of this study was to analyze the expression of Sprouty-2 (SPRY2) in the mammary gland and study its role in branching morphogenesis. Human breast epithelial cells, breast tissue and mouse mammary glands were used for expression studies using immunoblotting, real rime PCR and immunohistochemistry. Knockdown of SPRY2 in the breast epithelial stem cell line D492 was done by lentiviral transduction of shRNA constructs targeting SPRY2. Three dimensional culture of D492 with or without endothelial cells was done in reconstituted basement membrane matrix. We show that in the human breast, SPRY2 is predominantly expressed in the luminal epithelial cells of both ducts and lobuli. In the mouse mammary gland, SPRY2 expression is low or absent in the virgin state, while in the pregnant mammary gland SPRY2 is expressed at branching epithelial buds with increased expression during lactation. This expression pattern is closely associated with the activation of the EGFR pathway. Using D492 which generates branching structures in three-dimensional (3D) culture, we show that SPRY2 expression is low during initiation of branching with subsequent increase throughout the branching process. Immunostaining locates expression of phosphorylated SPRY2 and EGFR at the tip of lobular-like, branching ends. SPRY2 knockdown (KD) resulted in increased migration, increased pERK and larger and more complex branching structures indicating a loss of negative feedback control during branching morphogenesis. In D492 co-cultures with endothelial cells, D492 SPRY2 KD generates spindle-like colonies that bear hallmarks of epithelial to mesenchymal transition. These data indicate that SPRY2 is an important regulator of

  4. Expression and functional role of sprouty-2 in breast morphogenesis.

    Directory of Open Access Journals (Sweden)

    Valgardur Sigurdsson

    Full Text Available Branching morphogenesis is a mechanism used by many species for organogenesis and tissue maintenance. Receptor tyrosine kinases (RTKs, including epidermal growth factor receptor (EGFR and the sprouty protein family are believed to be critical regulators of branching morphogenesis. The aim of this study was to analyze the expression of Sprouty-2 (SPRY2 in the mammary gland and study its role in branching morphogenesis. Human breast epithelial cells, breast tissue and mouse mammary glands were used for expression studies using immunoblotting, real rime PCR and immunohistochemistry. Knockdown of SPRY2 in the breast epithelial stem cell line D492 was done by lentiviral transduction of shRNA constructs targeting SPRY2. Three dimensional culture of D492 with or without endothelial cells was done in reconstituted basement membrane matrix. We show that in the human breast, SPRY2 is predominantly expressed in the luminal epithelial cells of both ducts and lobuli. In the mouse mammary gland, SPRY2 expression is low or absent in the virgin state, while in the pregnant mammary gland SPRY2 is expressed at branching epithelial buds with increased expression during lactation. This expression pattern is closely associated with the activation of the EGFR pathway. Using D492 which generates branching structures in three-dimensional (3D culture, we show that SPRY2 expression is low during initiation of branching with subsequent increase throughout the branching process. Immunostaining locates expression of phosphorylated SPRY2 and EGFR at the tip of lobular-like, branching ends. SPRY2 knockdown (KD resulted in increased migration, increased pERK and larger and more complex branching structures indicating a loss of negative feedback control during branching morphogenesis. In D492 co-cultures with endothelial cells, D492 SPRY2 KD generates spindle-like colonies that bear hallmarks of epithelial to mesenchymal transition. These data indicate that SPRY2 is an

  5. Tremendous bleeding complication after vacuum-assisted sternal closure

    Directory of Open Access Journals (Sweden)

    Isgro Frank

    2011-02-01

    Full Text Available Abstract Vacuum-assisted closure (VAC of complex infected wounds has recently gained popularity among various surgical specialties. The system is based on the application of negative pressure by controlled suction to the wound surface. The effectiveness of the VAC System on microcirculation and the promotion of granulation tissue proliferation are proved. No contraindications for the use in deep sternal wounds in cardiac surgery are described. In our case report we illustrate a scenario were a patient developed severe bleeding from the ascending aorta by penetration of wire fragments in the vessel. We conclude that all free particles in the sternum have to be removed completely before negative pressure is used.

  6. Standard restrictive sternal precautions and modified sternal precautions had similar effects in people after cardiac surgery via median sternotomy (‘SMART’ Trial: a randomised trial

    Directory of Open Access Journals (Sweden)

    Md Ali Katijjahbe

    2018-04-01

    Full Text Available Question: In people who have undergone cardiac surgery via median sternotomy, does modifying usual sternal precautions to make them less restrictive improve physical function, pain, kinesiophobia and health-related quality of life? Design: Two-centre, randomised, controlled trial with concealed allocation, blinded assessors and intention-to-treat analysis. Participants: Seventy-two adults who had undergone cardiac surgery via a median sternotomy were included. Intervention: Participants were randomly allocated to one of two groups at 4 (SD 1 days after surgery. The control group received the usual advice to restrict their upper limb use for 4 to 6 weeks (ie, restrictive sternal precautions. The experimental group received advice to use pain and discomfort as the safe limits for their upper limb use during daily activities (ie, less restrictive precautions for the same period. Both groups received postoperative individualised education in hospital and via weekly telephone calls for 6 weeks. Outcome measures: The primary outcome was physical function assessed by the Short Physical Performance Battery. Secondary outcomes included upper limb function, pain, kinesophobia, and health-related quality of life. Outcomes were measured before hospital discharge and at 4 and 12 weeks postoperatively. Adherence to sternal precautions was recorded. Results: There were no statistically significant differences in physical function between the groups at 4 weeks (MD 1.0, 95% CI –0.2 to 2.3 and 12 weeks (MD 0.4, 95% CI –0.9 to 1.6 postoperatively. There were no statistically significant between-group differences in secondary outcomes. Conclusion: Modified (ie, less restrictive sternal precautions for people following cardiac surgery had similar effects on physical recovery, pain and health-related quality of life as usual restrictive sternal precautions. Similar outcomes can be anticipated regardless of whether people following cardiac surgery are managed with

  7. Plating versus wiring for fixation of traumatic rib and sternal fractures

    Directory of Open Access Journals (Sweden)

    Mostafa Kamel Abd-Elnaim

    2017-12-01

    Conclusions: Plating of rib and sternal fractures had better outcome than wiring, regarding better chest wall stability and restoration of chest contour; also it had shorter intensive care unit, hospital and ventilator days.

  8. Congenital superior sternal cleft repair using our modified Sally technique: A case report

    Directory of Open Access Journals (Sweden)

    Tomoyuki Kuwata

    2014-12-01

    Full Text Available We report the case of an 8-month-old male neonate who underwent reconstructive surgery for a congenital superior sternal cleft to decrease the risk of commotio cordis. With regard to use of the Sally technique for the repair of a relatively wide cleft (4 × 4 cm, we were concerned about respiratory problems caused by compression following closure of the sternal halves. By closing the sternal halves imperfectly, elevation of intrapleural pressure can be avoided to some extent. By bridging the surplus resected cartilage from the lower sternum over the gap of the upper sternum, the heart is protected by more rigid material. We recommend our modified Sally technique because it is both flexible and effective for sternal cleft repair.

  9. Solitary sternal lesions in breast cancer. Lesiones esternales unicas en cancer de mama

    Energy Technology Data Exchange (ETDEWEB)

    Morales, R; Cano, R; Mendoza, G [Instituto Peruano de Energia Nuclear, Lima (Peru); Guzman, C; Cotrina, M; Aguilar, C [Instituto Nacional de Enfermedades Neoplasicas, Lima (Peru)

    1993-12-01

    In a retrospective review of bone scans performed in 1740 patients with breast cancer from January 1988 to April 1993, twenty had a solitary sternal lesion. Etiology was found correlating this finding with pathology, x-rays and/or final outcome. Nineteen lesions were due to metastases and one to infection. This experience suggests that solitary sternal lesions in breast cancer patients are uncommon and are most frequently (95%) associated with malignant etiology. (Authors). 10 refs., 2 figs.

  10. Deep Sternal Wound Infection after Open-Heart Surgery: A 13-Year Single Institution Analysis.

    Science.gov (United States)

    Juhl, Alexander Andersen; Hody, Sofie; Videbaek, Tina Senholt; Damsgaard, Tine Engberg; Nielsen, Per Hostrup

    2017-04-20

    The present study aimed to compare the clinical outcome for patients with or without muscle flap reconstruction after deep sternal wound infection due to open-heart surgery. The study was a retrospective cohort study, including patients who developed deep sternal wound infection after open-heart surgery in the Western Denmark Region from 1999 to 2011. Journals of included patients were reviewed for clinical data regarding the treatment of their sternal defect. Patients were divided into two groups depending on whether they received a muscle-flap-based sternal reconstruction or traditional rewiring of the sternum. A total of 130 patients developed deep sternal wound infection in the study period. In all, 12 patients died before being discharged, leaving a total of 118 patients for analysis. Of these, 50 (42%) patients received muscle flap reconstruction. Muscle flap recipients had significantly longer total hospital stays (p <0.001). However, after receiving muscle flap reconstruction, patients were discharged after a median of 14 days, with 74% not needing additional surgery. It is difficult to predict which patients eventually require muscle flap reconstruction after deep sternal wound infection. Although patients receiving muscle flap reconstructions have longer hospital stays, they are quickly discharged after the reconstruction.

  11. Sternal instability measured with radiostereometric analysis. A study of method feasibility, accuracy and precision.

    Science.gov (United States)

    Vestergaard, Rikke Falsig; Søballe, Kjeld; Hasenkam, John Michael; Stilling, Maiken

    2018-05-18

    A small, but unstable, saw-gap may hinder bone-bridging and induce development of painful sternal dehiscence. We propose the use of Radiostereometric Analysis (RSA) for evaluation of sternal instability and present a method validation. Four bone analogs (phantoms) were sternotomized and tantalum beads were inserted in each half. The models were reunited with wire cerclage and placed in a radiolucent separation device. Stereoradiographs (n = 48) of the phantoms in 3 positions were recorded at 4 imposed separation points. The accuracy and precision was compared statistically and presented as translations along the 3 orthogonal axes. 7 sternotomized patients were evaluated for clinical RSA precision by double-examination stereoradiographs (n = 28). In the phantom study, we found no systematic error (p > 0.3) between the three phantom positions, and precision for evaluation of sternal separation was 0.02 mm. Phantom accuracy was mean 0.13 mm (SD 0.25). In the clinical study, we found a detection limit of 0.42 mm for sternal separation and of 2 mm for anterior-posterior dislocation of the sternal halves for the individual patient. RSA is a precise and low-dose image modality feasible for clinical evaluation of sternal stability in research. ClinicalTrials.gov Identifier: NCT02738437 , retrospectively registered.

  12. Polarized protein transport and lumen formation during epithelial tissue morphogenesis.

    Science.gov (United States)

    Blasky, Alex J; Mangan, Anthony; Prekeris, Rytis

    2015-01-01

    One of the major challenges in biology is to explain how complex tissues and organs arise from the collective action of individual polarized cells. The best-studied model of this process is the cross talk between individual epithelial cells during their polarization to form the multicellular epithelial lumen during tissue morphogenesis. Multiple mechanisms of apical lumen formation have been proposed. Some epithelial lumens form from preexisting polarized epithelial structures. However, de novo lumen formation from nonpolarized cells has recently emerged as an important driver of epithelial tissue morphogenesis, especially during the formation of small epithelial tubule networks. In this review, we discuss the latest findings regarding the mechanisms and regulation of de novo lumen formation in vitro and in vivo.

  13. Conserved RNA-Binding Proteins Required for Dendrite Morphogenesis in Caenorhabditis elegans Sensory Neurons

    Science.gov (United States)

    Antonacci, Simona; Forand, Daniel; Wolf, Margaret; Tyus, Courtney; Barney, Julia; Kellogg, Leah; Simon, Margo A.; Kerr, Genevieve; Wells, Kristen L.; Younes, Serena; Mortimer, Nathan T.; Olesnicky, Eugenia C.; Killian, Darrell J.

    2015-01-01

    The regulation of dendritic branching is critical for sensory reception, cell−cell communication within the nervous system, learning, memory, and behavior. Defects in dendrite morphology are associated with several neurologic disorders; thus, an understanding of the molecular mechanisms that govern dendrite morphogenesis is important. Recent investigations of dendrite morphogenesis have highlighted the importance of gene regulation at the posttranscriptional level. Because RNA-binding proteins mediate many posttranscriptional mechanisms, we decided to investigate the extent to which conserved RNA-binding proteins contribute to dendrite morphogenesis across phyla. Here we identify a core set of RNA-binding proteins that are important for dendrite morphogenesis in the PVD multidendritic sensory neuron in Caenorhabditis elegans. Homologs of each of these genes were previously identified as important in the Drosophila melanogaster dendritic arborization sensory neurons. Our results suggest that RNA processing, mRNA localization, mRNA stability, and translational control are all important mechanisms that contribute to dendrite morphogenesis, and we present a conserved set of RNA-binding proteins that regulate these processes in diverse animal species. Furthermore, homologs of these genes are expressed in the human brain, suggesting that these RNA-binding proteins are candidate regulators of dendrite development in humans. PMID:25673135

  14. Surveyed opinion of American trauma, orthopedic, and thoracic surgeons on rib and sternal fracture repair.

    Science.gov (United States)

    Mayberry, John C; Ham, L Bruce; Schipper, Paul H; Ellis, Thomas J; Mullins, Richard J

    2009-03-01

    Rib and sternal fracture repair are controversial. The opinion of surgeons regarding those patients who would benefit from repair is unknown. Members of the Eastern Association for the Surgery of Trauma, the Orthopedic Trauma Association, and thoracic surgeons (THS) affiliated with teaching hospitals in the United States were recruited to complete an electronic survey regarding rib and sternal fracture repair. Two hundred thirty-eight trauma surgeons (TRS), 97 orthopedic trauma surgeons (OTS), and 70 THS completed the survey. Eighty-two percent of TRS, 66% of OTS, and 71% of THS thought that rib fracture repair was indicated in selected patients. A greater proportion of surgeons thought that sternal fracture repair was indicated in selected patients (89% of TRS, 85% of OTS, and 95% of THS). Chest wall defect/pulmonary hernia (58%) and sternal fracture nonunion (>6 weeks) (68%) were the only two indications accepted by a majority of respondents. Twenty-six percent of surgeons reported that they had performed or assisted on a chest wall fracture repair, whereas 22% of surgeons were familiar with published randomized trials of the surgical repair of flail chest. Of surgeons who thought rib fracture or sternal fracture repair was rarely, if ever, indicated, 91% and 95%, respectively, specified that a randomized trial confirming efficacy would be necessary to change their negative opinion. A majority of surveyed surgeons reported that rib and sternal fracture repair is indicated in selected patients; however, a much smaller proportion indicated that they had performed the procedures. The published literature on surgical repair is sparse and unfamiliar to most surgeons. Barriers to surgical repair of rib and sternal fracture include a lack of expertise among TRS, lack of research of optimal techniques, and a dearth of randomized trials.

  15. Multifilament Cable Wire versus Conventional Wire for Sternal Closure in Patients Undergoing Major Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    You Na Oh

    2015-08-01

    Full Text Available Background: Stainless steel wiring remains the most popular technique for primary sternal closure. Recently, a multifilament cable wiring system (Pioneer Surgical Technology Inc., Marquette, MI, USA was introduced for sternal closure and has gained wide acceptance due to its superior resistance to tension. We aimed to compare conventional steel wiring to multifilament cable fixation for sternal closure in patients undergoing major cardiac surgery. Methods: Data were collected retrospectively on 1,354 patients who underwent sternal closure after major cardiac surgery, using either the multifilament cable wiring system or conventional steel wires between January 2009 and October 2010. The surgical outcomes of these two groups of patients were compared using propensity score matching based on 18 baseline patient characteristics. Results: Propensity score matching yielded 392 pairs of patients in the two groups whose baseline profiles showed no significant differences. No significant differences between the two groups were observed in the rates of early mortality (2.0% vs. 1.3%, p=0.578, major wound complications requiring reconstruction (1.3% vs. 1.3%, p>0.99, minor wound complications (3.6% vs. 2.0%, p=0.279, or mediastinitis (0.8% vs. 1.0%, p=1.00. Patients in the multifilament cable group had fewer sternal bleeding events than those in the conventional wire group, but this tendency was not statistically significant (4.3% vs. 7.4%, p=0.068. Conclusion: The surgical outcomes of sternal closure using multifilament cable wires were comparable to those observed when conventional steel wires were used. Therefore, the multifilament cable wiring system may be considered a viable option for sternal closure in patients undergoing major cardiac surgery.

  16. Multifilament Cable Wire versus Conventional Wire for Sternal Closure in Patients Undergoing Major Cardiac Surgery.

    Science.gov (United States)

    Oh, You Na; Ha, Keong Jun; Kim, Joon Bum; Jung, Sung-Ho; Choo, Suk Jung; Chung, Cheol Hyun; Lee, Jae Won

    2015-08-01

    Stainless steel wiring remains the most popular technique for primary sternal closure. Recently, a multifilament cable wiring system (Pioneer Surgical Technology Inc., Marquette, MI, USA) was introduced for sternal closure and has gained wide acceptance due to its superior resistance to tension. We aimed to compare conventional steel wiring to multifilament cable fixation for sternal closure in patients undergoing major cardiac surgery. Data were collected retrospectively on 1,354 patients who underwent sternal closure after major cardiac surgery, using either the multifilament cable wiring system or conventional steel wires between January 2009 and October 2010. The surgical outcomes of these two groups of patients were compared using propensity score matching based on 18 baseline patient characteristics. Propensity score matching yielded 392 pairs of patients in the two groups whose baseline profiles showed no significant differences. No significant differences between the two groups were observed in the rates of early mortality (2.0% vs. 1.3%, p=0.578), major wound complications requiring reconstruction (1.3% vs. 1.3%, p>0.99), minor wound complications (3.6% vs. 2.0%, p=0.279), or mediastinitis (0.8% vs. 1.0%, p=1.00). Patients in the multifilament cable group had fewer sternal bleeding events than those in the conventional wire group, but this tendency was not statistically significant (4.3% vs. 7.4%, p=0.068). The surgical outcomes of sternal closure using multifilament cable wires were comparable to those observed when conventional steel wires were used. Therefore, the multifilament cable wiring system may be considered a viable option for sternal closure in patients undergoing major cardiac surgery.

  17. Enhanced Sternal Healing via Platelet-Rich Plasma and Biodegradable Gelatin Hydrogel.

    Science.gov (United States)

    Shibata, Masafumi; Takagi, Gen; Kudo, Mitsuhiro; Kurita, Jiro; Kawamoto, Yoko; Miyagi, Yasuo; Kanazashi, Mikimoto; Sakatani, Takashi; Naito, Zenya; Tabata, Yasuhiko; Miyamoto, Masaaki; Nitta, Takashi

    2018-05-16

    Platelet-rich plasma (PRP) contains numerous growth factors and promotes bone fracture healing. The aim of this study was to evaluate the effectiveness of the controlled release of PRP from biodegradable gelatin hydrogel for promoting healing in a rabbit ischemic sternal model. PRP was prepared from the whole blood of a Japanese white rabbit. Sixteen rabbits were randomized into four groups (each n = 4) and all underwent median sternotomy and bilateral internal thoracic artery removal. Before the sternum was closed, the following solutions were applied between the sternum incisions in three of the groups: 30 mg of gelatin hydrogel incorporating 300 μL of phosphate-buffered saline, 300 μL of a solution form of PRP, or 30 mg of gelatin hydrogel incorporating 300 μL of PRP (PRP+Gel). The fourth group acted as a control. Sternal healing was evaluated by histology and micro-computed tomography 7 days after the intervention. The PRP+Gel group showed a significantly higher proportion of fibrosis within the fracture area (an indicator of sternal healing) than the other groups and a significantly higher mean intensity of osteocalcin. These results indicate that the controlled release of PRP from locally applied gelatin hydrogel was markedly effective in enhancing sternal healing in the early postoperative period. This novel therapy could potentially help prevent complications such as deep sternal wound infection and could result in early postoperative ambulation after median sternotomy.

  18. Secondary omental and pectoralis major double flap reconstruction following aggressive sternectomy for deep sternal wound infections after cardiac surgery

    Directory of Open Access Journals (Sweden)

    Shirasawa Bungo

    2011-04-01

    Full Text Available Abstract Background Deep sternal wound infection after cardiac surgery carries high morbidity and mortality. Our strategy for deep sternal wound infection is aggressive strenal debridement followed by vacuum-assisted closure (VAC therapy and omental-muscle flap reconstrucion. We describe this strategy and examine the outcome and long-term quality of life (QOL it achieves. Methods We retrospectively examined 16 patients treated for deep sternal wound infection between 2001 and 2007. The most recent nine patients were treated with total sternal resection followed by VAC therapy and secondary closure with omental-muscle flap reconstruction (recent group; whereas the former seven patients were treated with sternal preservation if possible, without VAC therapy, and four of these patients underwent primary closure (former group. We assessed long-term quality of life after DSWI by using the Short Form 36-Item Health Survey, Version 2 (SF36v2. Results One patient died and four required further surgery for recurrence of deep sternal wound infection in the former group. The duration of treatment for deep sternal wound infection in the recent group was significantly shorter than that in previous group (63.4 ± 54.1 days vs. 120.0 ± 31.8 days, respectively; p = 0.039. Despite aggressive sternal resection, the QOL of patients treated for DSWI was only minimally compromised compared with age-, sex-, surgical procedures-matched patients without deep sternal wound infection. Conclusions Aggressive sternal debridement followed by VAC therapy and secondary closure with an omental-muscle flap is effective for deep sternal wound infection. In this series, it resulted in a lower incidence of recurrent infection, shorter hospitalization, and it did not compromise long-term QOL greatly.

  19. Bilateral Subpectoral Interfascial Plane Catheters for Analgesia for Sternal Fractures: A Case Report.

    Science.gov (United States)

    Raza, Irfan; Narayanan, Madankumar; Venkataraju, Arun; Ciocarlan, Alexandra

    2016-01-01

    Sternal fractures occur after deceleration injuries such as falls and road traffic accidents. Recovery from isolated fractures is excellent, but mortality increases dramatically with concurrent chest injuries such as rib fractures and soft tissue injuries. Short-term complications include chest pain, which prevents patients from taking deep breaths and coughing, thereby predisposing them to chest infections. We present a case of a 73-year-old woman with sternal fracture in whom enteral analgesia was inadequate and who was intolerant to intravenous opiates. The patient was successfully treated with a continuous infusion of local anesthetic into the subpectoral interfascial plane. We also discuss the use and potential benefits of the subpectoral interfascial plane block in the treatment of pain from sternal fractures.

  20. [Vacuum-assisted closure therapy for the treatment of sternal wound infection after cardiac surgery].

    Science.gov (United States)

    Nishimura, K; Nakamura, Y; Harada, S; Saiki, M; Marumoto, A; Kanaoka, Y; Nishimura, M

    2009-11-01

    Sternal wound infection is still one of the critical and challenging complications after cardiac surgery. Vacuum-assisted closure (VAC) therapy is a unique and simple system that helps promote wound healing. We report 3 cases with the sternal wound infection after cardiac surgery, in which VAC therapy was applied between January, 2005 and April, 2007. Two of them had good response to VAC therapy and had their wound healed after 3 and 5 weeks, respectively. However, the remaining case, in which bilateral internal thoracic artery had been taken down for coronary artery bypass grafting (CABG) and osteomyelitis of the sternum was not well controlled, did not respond to VAC therapy. Our results suggested that VAC might facilitate wound healing of the patients with sternal wound infection only after abscess was drained and opened, while it might not be useful for the patents with osteomyelitis.

  1. The ureteric bud epithelium: morphogenesis and roles in metanephric kidney patterning.

    Science.gov (United States)

    Nagalakshmi, Vidya K; Yu, Jing

    2015-03-01

    The mammalian metanephric kidney is composed of two epithelial components, the collecting duct system and the nephron epithelium, that differentiate from two different tissues -the ureteric bud epithelium and the nephron progenitors, respectively-of intermediate mesoderm origin. The collecting duct system is generated through reiterative ureteric bud branching morphogenesis, whereas the nephron epithelium is formed in a process termed nephrogenesis, which is initiated with the mesenchymal-epithelial transition of the nephron progenitors. Ureteric bud branching morphogenesis is regulated by nephron progenitors, and in return, the ureteric bud epithelium regulates nephrogenesis. The metanephric kidney is physiologically divided along the corticomedullary axis into subcompartments that are enriched with specific segments of these two epithelial structures. Here, we provide an overview of the major molecular and cellular processes underlying the morphogenesis and patterning of the ureteric bud epithelium and its roles in the cortico-medullary patterning of the metanephric kidney. © 2015 Wiley Periodicals, Inc.

  2. Reliability of sternal instability scale (SIS) for transverse sternotomy in lung transplantation (LTX).

    Science.gov (United States)

    Fuller, Louise M; El-Ansary, Doa; Button, Brenda; Bondarenko, Janet; Marasco, Silvana; Snell, Greg; Holland, Anne E

    2018-01-25

    A surgical incision for bilateral sequential lung transplantation (BSLTX) is the "clam shell" (CSI) approach via bilateral anterior thoracotomies and a transverse sternotomy to allow for sequential replacement of the lungs. This can be associated with significant post-operative pain, bony overriding or sternal instability. The sternal instability scale (SIS) is a non-invasive manual assessment tool that can be used to detect early bony non-union or instability following CSI; however, its reliability is unknown. This prospective blinded reliability study aimed to assess intra-rater and inter-rater reliability of the SIS following lung transplantation. Participants post BSLTX aged older than 18 years underwent sternal assessment utilizing the SIS. Two assessors examined the sternum using a standardized protocol at two separate time points with a test-re-test time of 48 hours. The outcome measure was SIS tool using four categories from 0 (clinically stable) to 3 (separated sternum with overriding). In total, 20 participants (75% female) with a mean age of 48 years (SD 17) and mean pain score of 3 out of 10 were included, 60% having well healed wounds and 25% reporting symptoms of sternal clicking. The most painful self-reported painful activity was coughing. The SIS demonstrated excellent reliability with a kappa = 0.91 by different assessors on the same day, and kappa = 0.83 for assessments by the same assessor on different days. The SIS is a reliable manual assessment tool for evaluation of sternal instability after CSI following BSLTX and may facilitate the timely detection and management of sternal instability.

  3. Vacuum-assisted closure in the treatment of sternal wound infection after cardiac surgery.

    Science.gov (United States)

    Simek, Martin; Nemec, Petr; Zalesak, Bohumil; Kalab, Martin; Hajek, Roman; Jecminkova, Lenka; Kolar, Milan

    2007-12-01

    Vacuum-assisted closure (VAC) was primarily designed for the treatment of pressure ulcers or chronic, debilitating wounds. Recently, VAC has become an encouraging treatment modality for sternal wound infection after cardiac surgery, providing superior results to conventional treatment strategies. From November 2004 to September 2006, 34 patients, undergoing VAC therapy for sternal wound infection following cardiac surgery, were prospectively evaluated. Ten patients (29 %) were treated for superficial sternal wound infection and 24 (71 %) for deep sternal wound infection. The median age was 69.9 years (range 48 to 82) and the median BMI was 33.4 kg/m(2) (range 28 to 41). Twenty patients (59 %) were women and 19 patients (59 %) were diabetics. Owing to sternal wound infection complications, 16 patients (47 %) were readmitted to the department. VAC was used following the previous failure of the conventional treatment strategy in 7 patients (21 %). Thirty-three patients (97 %) were treated successfully. One patient (3 %) died of multiple organ failure. The overall length of hospitalization was 34.6 days (range 9 to 62). The median number of dressing changes was 4.6 (range 3 to 10). The median VAC treatment time until surgical closure was 9.2 days (range 6 to 21 days). VAC therapy was solely used as a bridge to definite wound closure. Three patients (9 %) with chronic fistula were re-admitted 1 to 6 months after VAC therapy. VAC therapy is a safe and reliable option in the treatment of sternal wound infection in cardiac surgery. VAC therapy should be considered an effective adjunct to conventional treatment modalities for the treatment of extensive and life-threatening wound infections following cardiac surgery, particularly in the presence of risk factors.

  4. Reconstruction of Chest Wall by Cryopreserved Sternal Allograft after Resection of Aneurysmal Bone Cyst of Sternum

    Directory of Open Access Journals (Sweden)

    Kambiz Sheikhy

    2017-01-01

    Full Text Available A 20-year-old female was referred to our hospital due to deformity and bulging in anterior aspect of chest wall in sternal area. Chest X-ray and CT scan confirmed a large mass with destruction of sternum. Pathologic diagnosis after incisional biopsy was compatible with aneurysmal bone cyst. We resected sternum completely and reconstructed large anterior defect by a cryopreserved sternal allograft. In follow-up of patient there was no unstability of chest wall with good cosmetic result.

  5. CRIM1 Complexes with ß-catenin and Cadherins, Stabilizes Cell-Cell Junctions and Is Critical for Neural Morphogenesis

    OpenAIRE

    Ponferrada, Virgilio G.; Fan, Jieqing; Vallance, Jefferson E.; Hu, Shengyong; Mamedova, Aygun; Rankin, Scott A.; Kofron, Matthew; Zorn, Aaron M.; Hegde, Rashmi S.; Lang, Richard A.

    2012-01-01

    In multicellular organisms, morphogenesis is a highly coordinated process that requires dynamically regulated adhesion between cells. An excellent example of cellular morphogenesis is the formation of the neural tube from the flattened epithelium of the neural plate. Cysteine-rich motor neuron protein 1 (CRIM1) is a single-pass (type 1) transmembrane protein that is expressed in neural structures beginning at the neural plate stage. In the frog Xenopus laevis, loss of function studies using C...

  6. On the Morphogenesis of Feathers

    Science.gov (United States)

    Yu, Mingke; Wu, Ping; Widelitz, Randall B.; Chuong, Cheng-Ming

    2015-01-01

    The most unique character of the feather is its highly ordered hierarchical branched structure1, 2. This evolutionary novelty confers flight function to birds3–5. Recent discoveries of fossils in China have prompted keen interest in the origin and evolution of feathers6–14. However, controversy arises whether the irregularly branched integumentary fibers on dinosaurs such as Sinornithosaurus are truly feathers6, 11, and whether an integumentary appendage with a major central shaft and notched edges is a non-avian feather or a proto-feather8–10. Here we take a developmental approach to analyze molecular mechanisms in feather branching morphogenesis. We have used the replication competent avian sarcoma (RCAS) retrovirus15 to efficiently deliver exogenous genes to regenerating chicken flight feather follicles. We show that the antagonistic balance between noggin and bone morphogenetic protein 4 (BMP4) plays a critical role in feather branching, with BMP4 promoting rachis formation and barb fusion, and noggin enhancing rachis and barb branching. Furthermore we show that sonic hedgehog (SHH) is essential for apoptosis of the marginal plate epithelia to become spaces between barbs. Our analyses show the molecular pathways underlying the topological transformation of feathers from cylindrical epithelia to the hierarchical branched structures, and provide first clues on the possible developmental mechanisms in the evolution of feather forms. PMID:12442169

  7. Mesenchymal Stem/Stromal Cells from Discarded Neonatal Sternal Tissue: In Vitro Characterization and Angiogenic Properties

    Directory of Open Access Journals (Sweden)

    Shuyun Wang

    2016-01-01

    Full Text Available Autologous and nonautologous bone marrow mesenchymal stem/stromal cells (MSCs are being evaluated as proangiogenic agents for ischemic and vascular disease in adults but not in children. A significant number of newborns and infants with critical congenital heart disease who undergo cardiac surgery already have or are at risk of developing conditions related to inadequate tissue perfusion. During neonatal cardiac surgery, a small amount of sternal tissue is usually discarded. Here we demonstrate that MSCs can be isolated from human neonatal sternal tissue using a nonenzymatic explant culture method. Neonatal sternal bone MSCs (sbMSCs were clonogenic, had a surface marker expression profile that was characteristic of bone marrow MSCs, were multipotent, and expressed pluripotency-related genes at low levels. Neonatal sbMSCs also demonstrated in vitro proangiogenic properties. Sternal bone MSCs cooperated with human umbilical vein endothelial cells (HUVECs to form 3D networks and tubes in vitro. Conditioned media from sbMSCs cultured in hypoxia also promoted HUVEC survival and migration. Given the neonatal source, ease of isolation, and proangiogenic properties, sbMSCs may have relevance to therapeutic applications.

  8. Role of Negative-Pressure Wound Therapy in Deep Sternal Wound Infection After Open Heart Surgery

    Directory of Open Access Journals (Sweden)

    Cemalettin Aydın

    2013-08-01

    Full Text Available Introduction: Mediastinitis is a devastating complication in open heart surgery. The most common treatments after debridement are rewiring with antibiotic irrigation. Vacuum assisted closure therapy is a recently introduced technique that promotes the healing of difficult wounds, including post-sternotomy mediastinitis.Patients and Methods: Forty one patients with deep sternal wound infection were divided into two groups based on the treatment method used. Twenty two patients with post-cardio to my deep sternal wound infection were treated primarily by vacuum assisted closure method (group A and 19 patients with deep sternal wound infection who received closed mediastinal irrigation were treated with antibiotics (group B between January 2006 and January 2010.Results: The two groups were compared. Three patients died during treatment in group B. The median healing time was significantly shorter in group A (mean, 13.5 ± 3.2 days compared to 18 days (mean, 21.2 ± 16.4 days in group B (p< 0.001. Deep sternal wound infection showed no recurrences after the vacuum treatment, while 7 (24% patients in group B suffered recurrences. Hospital stay was significantly shorter in group A (median, 30.5 days; mean, 32.2 ± 11.3 days vs. median, 45 days; mean, 49.2 ± 19.3 days (p= 0.001.Conclusion: A significantly shorter healing time was confirmed with vacuum assisted closure. Hospital stay remained significantly shorter in group A (35 vs. 46 days.

  9. A clinical study of short-term sternal photoplethysmography: recordings from patients with obstructive airways diseases

    DEFF Research Database (Denmark)

    Chreiteh, Shadi; Saadi, Dorthe Bodholt; Belhage, Bo

    2016-01-01

    and commercially accepted range. We then compared the SpO2 levels simultaneously obtained from the sternal PPGs and a commercially available finger pulse oximeter on 28 admitted patients with either asthma or Chronic Obstructive Pulmonary Disease (COPD). The Pearson correlation between the SpO2 levels estimated...

  10. Sternal wound complications after primary isolated myocardial revascularization: the importance of the post-operative variables.

    NARCIS (Netherlands)

    Noyez, L.; Druten, J.A.M. van; Mulder, J.; Schroen, A.M.; Skotnicki, S.H.; Brouwer, R.

    2001-01-01

    OBJECTIVE: Select pre-, peri-, and post-operative variables, predictive for sternal wound complications (SWC), in a clinical setting. METHODS: We analyzed pre-, peri-, and post-operative data of 3815 patients who underwent a primary isolated bypass grafting. 100 patients (2.6%) had post-operative

  11. Deep sternal wound infection after coronary artery bypass surgery: management and risk factor analysis for mortality.

    Science.gov (United States)

    Yumun, Gunduz; Erdolu, Burak; Toktas, Faruk; Eris, Cuneyt; Ay, Derih; Turk, Tamer; As, Ahmet Kagan

    2014-08-01

    Deep sternal wound infection is a life-threatening complication after cardiac surgery. The aim of this study was to investigate the factors leading to mortality, and to explore wound management techniques on deep sternal wound infection after coronary artery bypass surgery. Between 2008 and 2013, 58 patients with deep sternal wound infection were analyzed. Risk factors for mortality and morbidity including age, gender, body mass index, smoking status, chronic renal failure, hypertension, diabetes, and treatment choice were investigated. In this study, 19 patients (32.7%) were treated by primary surgical closure (PSC), and 39 patients (67.3%) were treated by delayed surgical closure following a vacuum-assisted closure system (VAC). Preoperative patient characteristics were similar between the groups. Fourteen patients (24.1%) died in the postoperative first month. The mortality rate and mean duration of hospitalization in the PSC group was higher than in the VAC group (P = .026, P = .034). Significant risk factors for mortality were additional operation, diabetes mellitus, and a high level of EuroSCORE. Delayed surgical closure following VAC therapy may be associated with shorter hospitalization and lower mortality in patients with deep sternal wound infection. Additional operation, diabetes mellitus, and a high level of EuroSCORE were associated with mortality.

  12. Chest reconstruction using a custom-designed polyethylene 3D implant after resection of the sternal manubrium

    Directory of Open Access Journals (Sweden)

    Lipińska J

    2017-08-01

    Full Text Available Joanna Lipińska,1 Leszek Kutwin,1 Marcin Wawrzycki,1 Leszek Olbrzymek,2 Sławomir Jabłoński1 1Department of Thoracic Surgery, General and Oncological Surgery, Medical University of Lodz, 2Ledo, Lodz, Poland Introduction: Resection of manubrium or body of the sternum is associated with a necessity of chest wall reconstruction. Large sternal defects require the use of different types of implants to ensure acceptable esthetic effect for the patient and chest stabilization. Aim: The purpose of this case report is to present a novel method of reconstruction of manubrium removed due to renal cancer metastasis to the sternum.Case: We present the case of a patient, who had underwent right nephrectomy for clear cell kidney cancer, diagnosed with a metastatic tumor in the sternum resulting in destruction of manubrium. The patient undergone tumor resection with primary reconstruction with an individual prosthesis. Sternal defect was filled with a personalized, computed tomography scan-based 3D-milled implant made of polyethylene.Results: Sternal reconstruction was uneventful. The patient endured surgery well, and has been under surveillance in outpatient clinic, without any respiration disorders, implant movement or local recurrence.Conclusion: Custom-designed sternal implants created by 3D technique constitute an interesting alternative for previous methods of filling defects after resection of a tumor in this location. Keywords: 3D-milled implant, thoracoplasty, reconstructive surgery, chest reconstruction, sternal metastasis, sternal implant, sternal tumor 

  13. A global sensitivity analysis approach for morphogenesis models

    KAUST Repository

    Boas, Sonja E. M.; Navarro, Marí a; Merks, Roeland M. H.; Blom, Joke G.

    2015-01-01

    Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand

  14. Programming Morphogenesis through Systems and Synthetic Biology.

    Science.gov (United States)

    Velazquez, Jeremy J; Su, Emily; Cahan, Patrick; Ebrahimkhani, Mo R

    2018-04-01

    Mammalian tissue development is an intricate, spatiotemporal process of self-organization that emerges from gene regulatory networks of differentiating stem cells. A major goal in stem cell biology is to gain a sufficient understanding of gene regulatory networks and cell-cell interactions to enable the reliable and robust engineering of morphogenesis. Here, we review advances in synthetic biology, single cell genomics, and multiscale modeling, which, when synthesized, provide a framework to achieve the ambitious goal of programming morphogenesis in complex tissues and organoids. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Dynamics of Spore Coat Morphogenesis in Bacillus subtilis

    Science.gov (United States)

    McKenney, Peter T.; Eichenberger, Patrick

    2011-01-01

    SUMMARY Spores of Bacillus subtilis are encased in a protective coat made up of at least 70 proteins. The structure of the spore coat has been examined using a variety of genetic, imaging and biochemical techniques, however, the majority of these studies have focused on mature spores. In this study we use a library of 41 spore coat proteins fused to the Green Fluorescent Protein (GFP) to examine spore coat morphogenesis over the time-course of sporulation. We found considerable diversity in the localization dynamics of coat proteins and were able to establish 6 classes based on localization kinetics. Localization dynamics correlate well with the known transcriptional regulators of coat gene expression. Previously, we described the existence of multiple layers in the mature spore coat. Here, we find that the spore coat initially assembles a scaffold that is organized into multiple layers on one pole of the spore. The coat then encases the spore in multiple coordinated waves. Encasement is driven, at least partially, by transcription of coat genes and deletion of sporulation transcription factors arrests encasement. We also identify the trans-compartment SpoIIIAH-SpoIIQ channel as necessary for encasement. This is the first demonstration of a forespore contribution to spore coat morphogenesis. PMID:22171814

  16. Sternal Osteomyelitis and Abscess Caused by Elbowing during a Basketball Game

    Directory of Open Access Journals (Sweden)

    Hideo Ichimura

    2012-01-01

    Full Text Available A 15-year-old boy was referred to our hospital for further investigation and treatment of sternal osteomyelitis due to blunt chest trauma, more specifically elbowing during a basketball game 19 days earlier. On an initial presentation, his chest was markedly swollen and chest computed tomography demonstrated a sternal fracture and massive fluid collection in the chest wall. Since his general condition remained fairly good, we initially selected minimal drainage concomitant with antibiotics; if it was unsuccessful, we planned to switch to a more radical debridement procedure. The patient recovered without further invasive intervention and was discharged on postoperative day 26. There is no sign of recurrence six months after operation. This case report indicates that minimal drainage would be a good option for treatment in a phased strategy.

  17. Correlated evolution of sternal keel length and ilium length in birds

    Directory of Open Access Journals (Sweden)

    Tao Zhao

    2017-07-01

    Full Text Available The interplay between the pectoral module (the pectoral girdle and limbs and the pelvic module (the pelvic girdle and limbs plays a key role in shaping avian evolution, but prior empirical studies on trait covariation between the two modules are limited. Here we empirically test whether (size-corrected sternal keel length and ilium length are correlated during avian evolution using phylogenetic comparative methods. Our analyses on extant birds and Mesozoic birds both recover a significantly positive correlation. The results provide new evidence regarding the integration between the pelvic and pectoral modules. The correlated evolution of sternal keel length and ilium length may serve as a mechanism to cope with the effect on performance caused by a tradeoff in muscle mass between the pectoral and pelvic modules, via changing moment arms of muscles that function in flight and in terrestrial locomotion.

  18. La tuberculose sternale: à propos de 2 cas | Ouarssani | Pan African ...

    African Journals Online (AJOL)

    On rapporte deux cas de tuberculose sternale âgés respectivement de 45 ans et de 10ans, colligés au service de pneumologie, l'examen histologique et bactériologique ont permis d'affirmer le diagnostic de tuberculose, et le traitement antibacillaire a permis une évolution favorable .A la lumière de ces observations, les ...

  19. A review of eleven cases of tuberculosis presenting as sternal wound abscess after open heart surgery.

    Science.gov (United States)

    Tabaja, Hussam; Hajar, Zeina; Kanj, Souha S

    2017-10-01

    Sternal wound infection with Mycobacterium tuberculosis is an uncommon yet highly challenging disease that can be quite insidious with various presentations. We hereby provide a review of 10 cases in current literature and describe an additional case which illustrates the difficulties associated with diagnosis. We used PubMed and Google search engine to search the literature for all published papers reporting on cases of sternal M. tuberculosis infections post open-heart surgeries. A total of 11 cases were presented, including a case of our own. The majority were males and were exposed to endemic areas. The average age was 59.6 ± 15.5 years. Coronary artery bypass surgery accounted for 73% of procedures and the average time to symptoms onset was 12.2 ± 16.6 months. Diabetes was the most reported non-cardiac comorbidity. Presenting symptoms varied and only 5 patients had other organs involved. Blood tests and radiographic studies were neither sensitive nor specific. M. tuberculosis culture on debrided tissues was the most sensitive test but often forgotten initially. Diagnostic delay was seen in almost all cases, often leading to unnecessary courses of antibiotics and aggressive surgical interventions. Finally, all patients responded well to anti-tuberculosis treatment, with reported treatment duration ranging from 9 to 12 months. M. tuberculosis infection of the sternum should be suspected in late-onset sternal wound infections post open-heart surgery especially when the course is chronic and indolent.

  20. MR analysis of sternal bone marrow using STIR in hematologic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Kozawa, Eito [Saitama Medical School, Moroyama (Japan)

    1998-12-01

    The magnetic resonance (MR) signal intensity pattern of sternal bone marrow was examined in 21 normal volunteers and 10 patients with aplastic anemia (n=4), multiple myeloma (2), AML (2), gammaglobulinemia (1) and MDS (1) using a sagittal STIR sequence. Double Echo STIR images (TR/TI/TE/NEX=2000/180/20, 100/1) were obtained with a CP body array coil. Craniocaudal phase-encoding with a handmade positioning device effectively avoided overlapping artifacts due to cardiac pulsation. In the normal volunteers, age showed a significant inverse correlation with the calculated SIR (signal intensity ratio of bone marrow relative to subcutaneous fat) using STIR with short TE. The SIR in the sternal body was significantly higher than that in the manubrium (p<0.05). Knowledge of the sternal bone marrow distribution according to age is useful for evaluating hematologic diseases. The proposed method provided high spatial resolution and an excellent bone marrow signal, and may be useful for determining site for aspiration. (author)

  1. Location of Sternal Fractures as a Possible Marker for Associated Injuries

    Directory of Open Access Journals (Sweden)

    Max J. Scheyerer

    2013-01-01

    Full Text Available Introduction. Sternal fractures often occur together with serious and life-threatening additional injuries. This retrospective study was designed to assess concomitant injuries and develop a correlation between fracture location and the severity of injury. Methods. All patients ( diagnosed with a fracture of the sternum by means of a CT scan were analysed with respect to accident circumstances, fracture morphology and topography, associated injuries, and outcome. Results. Isolated sternal fractures occurred in 9%. In all other admissions, concomitant injuries were diagnosed: mainly rip fractures (64%, injury to the head (48%, the thoracic spine (38%, lumbar spine (27%, and cervical spine (22%. Predominant fracture location was the manubrium sterni. In these locations, the observed mean ISS was the highest. They were strongly associated with thoracic spine and other chest injuries. Furthermore, the incidence of head injuries was significantly higher. ICU admission was significantly higher in patients with manubrium sterni fractures. Conclusion. Sternal fractures are frequently associated with other injuries. It appears that the fracture location can provide important information regarding concomitant injuries. In particular, in fractures of manubrium sterni, the need for further detailed clinical and radiologic workup is necessary to detect the frequently associated injuries and reduce the increased mortality.

  2. Impact of deep sternal wound infection management with vacuum-assisted closure therapy followed by sternal osteosynthesis: a 15-year review of 23,499 sternotomies.

    Science.gov (United States)

    Baillot, Richard; Cloutier, Daniel; Montalin, Livia; Côté, Louise; Lellouche, François; Houde, Chanel; Gaudreau, Geneviève; Voisine, Pierre

    2010-04-01

    This study was undertaken to examine the outcome of patients with deep sternal wound infection (DSWI) now treated with vacuum-assisted closure (VAC) therapy as a bridge to sternal osteosynthesis with horizontal titanium plate fixation. From 1992 to 2007, a consecutive cohort of 23,499 patients underwent open-heart surgery (OHS) in our institution. The period under study was divided in two according to the use of therapeutic modalities: conventional (1992-2001, N=118 DSWI): debridement/drainage with primary closure and irrigation (N=37), debridement/drainage, open packing followed by pectoralis myocutaneous flaps (PMFs) (N=81); contemporary (2002-2007, N=149 DSWI): conventional treatment (N=24) and VAC therapy (N=125/83.8%). VAC was followed by sternal osteosynthesis with horizontal titanium plates in 92 patients (61.7%). DSWI was diagnosed in 267 out of 23 499 (1.1%) patients of our entire series according to Center for Disease Control - Atlanta (CDC) criteria, 118 out of 13 180 (0.9%) in the first and 149 out of 10 319 (1.4%) in the second period (p=0.001). Hospital mortality (N=267/23,499) has been 10.25% for the entire cohort under study without any difference between groups (1992-2001: 11.4%; 2002-2007: 9.1%, p=0.67). More recently, VAC therapy (N=125) was associated with a lower mortality (4.8% vs 14.1%, p=0.01). Stepwise multivariable logistic regression analysis for both periods revealed that prolonged intubation in the intensive care unit (ICU), use of bilateral internal thoracic artery grafting (BIMA), diabetes, re-operation for bleeding and body mass index (BMI) >30 kgm(-2) are the most powerful predictors of DSWI. In the more recently treated patients using VAC therapy, combined procedures (valve and graft) also emerged as a significant predictor. For the entire study, Staphylococcus epidermidis (49.6%) has been the most frequently identified pathogen, followed by Staphylococcus aureus (38.8%). Methicillin-resistant S.aureus (MRSA) was observed in 4

  3. Computational models of airway branching morphogenesis.

    Science.gov (United States)

    Varner, Victor D; Nelson, Celeste M

    2017-07-01

    The bronchial network of the mammalian lung consists of millions of dichotomous branches arranged in a highly complex, space-filling tree. Recent computational models of branching morphogenesis in the lung have helped uncover the biological mechanisms that construct this ramified architecture. In this review, we focus on three different theoretical approaches - geometric modeling, reaction-diffusion modeling, and continuum mechanical modeling - and discuss how, taken together, these models have identified the geometric principles necessary to build an efficient bronchial network, as well as the patterning mechanisms that specify airway geometry in the developing embryo. We emphasize models that are integrated with biological experiments and suggest how recent progress in computational modeling has advanced our understanding of airway branching morphogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Imaging morphogenesis: technological advances and biological insights.

    Science.gov (United States)

    Keller, Philipp J

    2013-06-07

    Morphogenesis, the development of the shape of an organism, is a dynamic process on a multitude of scales, from fast subcellular rearrangements and cell movements to slow structural changes at the whole-organism level. Live-imaging approaches based on light microscopy reveal the intricate dynamics of this process and are thus indispensable for investigating the underlying mechanisms. This Review discusses emerging imaging techniques that can record morphogenesis at temporal scales from seconds to days and at spatial scales from hundreds of nanometers to several millimeters. To unlock their full potential, these methods need to be matched with new computational approaches and physical models that help convert highly complex image data sets into biological insights.

  5. Apoptosis during budding morphogenesis of dentition

    Czech Academy of Sciences Publication Activity Database

    Peterková, Renata; Peterka, Miroslav; Viriot, L.; Lesot, H.

    2002-01-01

    Roč. 70, č. 7 (2002), s. 353 ISSN 0301-4681. [International Conference of the International Society of Differentiation /12./. Lyon, France, 14.09.2002-17.09.2002] R&D Projects: GA ČR GA304/02/0448 Institutional research plan: CEZ:AV0Z5039906 Keywords : morphogenesis of dentition Subject RIV: FF - HEENT, Dentistry Impact factor: 2.078, year: 2002

  6. Sternal Healing after Coronary Artery Bypass Grafting Using Bilateral Internal Thoracic Arteries: Assessment by Computed Tomography Scan

    Directory of Open Access Journals (Sweden)

    Yoon Cheol Shin

    2015-02-01

    Full Text Available Background: This study aimed to investigate sternal healing over time and the incidence of poor sternal healing in patients undergoing coronary artery bypass graft (CABG surgery using bilateral internal thoracic arteries. Methods: This study enrolled 197 patients who underwent isolated CABG using skeletonized bilateral internal thoracic arteries (sBITA from 2006 through 2009. Postoperative computed tomography (CT angiography was performed on all patients at monthly intervals for three to six months after surgery. In 108 patients, an additional CT study was performed 24 to 48 months after surgery. The axial CT images were used to score sternal fusion at the manubrium, the upper sternum, and the lower sternum. These scores were added to evaluate overall healing: a score of 0 to 1 reflected poor healing, a score of 2 to 4 was defined as fair healing, and a score of 5 to 6 indicated complete healing. Medical records were also retrospectively reviewed to identify perioperative variables associated with poor early sternal healing. Results: Three to six months after surgery, the average total score of sternal healing was 2.07±1.52 and 68 patients (34.5% showed poor healing. Poor healing was most frequently found in the manubrium, which was scored as zero in 72.6% of patients. In multivariate analysis, the factors associated with poor early healing were shorter post-surgery time, older age, diabetes mellitus, and postoperative renal dysfunction. In later CT images, the average sternal healing score improved to 5.88±0.38 and complete healing was observed in 98.2% of patients. Conclusion: Complete sternal healing takes more than three months after a median sternotomy for CABG using sBITA. Healing is most delayed in the manubrium.

  7. Differentiated roles for MreB-actin isologues and autolytic enzymes in Bacillus subtilis morphogenesis.

    Science.gov (United States)

    Domínguez-Cuevas, Patricia; Porcelli, Ida; Daniel, Richard A; Errington, Jeff

    2013-09-01

    Cell morphogenesis in most bacteria is governed by spatiotemporal growth regulation of the peptidoglycan cell wall layer. Much is known about peptidoglycan synthesis but regulation of its turnover by hydrolytic enzymes is much less well understood. Bacillus subtilis has a multitude of such enzymes. Two of the best characterized are CwlO and LytE: cells lacking both enzymes have a lethal block in cell elongation. Here we show that activity of CwlO is regulated by an ABC transporter, FtsEX, which is required for cell elongation, unlike cell division as in Escherichia coli. Actin-like MreB proteins are thought to play a key role in orchestrating cell wall morphogenesis. B. subtilis has three MreB isologues with partially differentiated functions. We now show that the three MreB isologues have differential roles in regulation of the CwlO and LytE systems and that autolysins control different aspects of cell morphogenesis. The results add major autolytic activities to the growing list of functions controlled by MreB isologues in bacteria and provide new insights into the different specialized functions of essential cell wall autolysins. © 2013 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

  8. Airway branching morphogenesis in three dimensional culture

    Directory of Open Access Journals (Sweden)

    Gudjonsson Thorarinn

    2010-11-01

    Full Text Available Abstract Background Lungs develop from the fetal digestive tract where epithelium invades the vascular rich stroma in a process called branching morphogenesis. In organogenesis, endothelial cells have been shown to be important for morphogenesis and the maintenance of organ structure. The aim of this study was to recapitulate human lung morphogenesis in vitro by establishing a three dimensional (3D co-culture model where lung epithelial cells were cultured in endothelial-rich stroma. Methods We used a human bronchial epithelial cell line (VA10 recently developed in our laboratory. This cell line cell line maintains a predominant basal cell phenotype, expressing p63 and other basal markers such as cytokeratin-5 and -14. Here, we cultured VA10 with human umbilical vein endothelial cells (HUVECs, to mimic the close interaction between these cell types during lung development. Morphogenesis and differentiation was monitored by phase contrast microscopy, immunostainings and confocal imaging. Results We found that in co-culture with endothelial cells, the VA10 cells generated bronchioalveolar like structures, suggesting that lung epithelial branching is facilitated by the presence of endothelial cells. The VA10 derived epithelial structures display various complex patterns of branching and show partial alveolar type-II differentiation with pro-Surfactant-C expression. The epithelial origin of the branching VA10 colonies was confirmed by immunostaining. These bronchioalveolar-like structures were polarized with respect to integrin expression at the cell-matrix interface. The endothelial-induced branching was mediated by soluble factors. Furthermore, fibroblast growth factor receptor-2 (FGFR-2 and sprouty-2 were expressed at the growing tips of the branching structures and the branching was inhibited by the FGFR-small molecule inhibitor SU5402. Discussion In this study we show that a human lung epithelial cell line can be induced by endothelial cells to

  9. Normal morphogenesis of epithelial tissues and progression of epithelial tumors

    Science.gov (United States)

    Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A.

    2011-01-01

    Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted. PMID:21898857

  10. Skeletal height estimation from regression analysis of sternal lengths in a Northwest Indian population of Chandigarh region: a postmortem study.

    Science.gov (United States)

    Singh, Jagmahender; Pathak, R K; Chavali, Krishnadutt H

    2011-03-20

    Skeletal height estimation from regression analysis of eight sternal lengths in the subjects of Chandigarh zone of Northwest India is the topic of discussion in this study. Analysis of eight sternal lengths (length of manubrium, length of mesosternum, combined length of manubrium and mesosternum, total sternal length and first four intercostals lengths of mesosternum) measured from 252 male and 91 female sternums obtained at postmortems revealed that mean cadaver stature and sternal lengths were more in North Indians and males than the South Indians and females. Except intercostal lengths, all the sternal lengths were positively correlated with stature of the deceased in both sexes (P regression analysis of sternal lengths was found more useful than the linear regression for stature estimation. Using multivariate regression analysis, the combined length of manubrium and mesosternum in both sexes and the length of manubrium along with 2nd and 3rd intercostal lengths of mesosternum in males were selected as best estimators of stature. Nonetheless, the stature of males can be predicted with SEE of 6.66 (R(2) = 0.16, r = 0.318) from combination of MBL+BL_3+LM+BL_2, and in females from MBL only, it can be estimated with SEE of 6.65 (R(2) = 0.10, r = 0.318), whereas from the multiple regression analysis of pooled data, stature can be known with SEE of 6.97 (R(2) = 0.387, r = 575) from the combination of MBL+LM+BL_2+TSL+BL_3. The R(2) and F-ratio were found to be statistically significant for almost all the variables in both the sexes, except 4th intercostal length in males and 2nd to 4th intercostal lengths in females. The 'major' sternal lengths were more useful than the 'minor' ones for stature estimation The universal regression analysis used by Kanchan et al. [39] when applied to sternal lengths, gave satisfactory estimates of stature for males only but female stature was comparatively better estimated from simple linear regressions. But they are not proposed for the

  11. A new cable-tie based sternal closure system: description of the device, technique of implantation and first clinical evaluation

    Directory of Open Access Journals (Sweden)

    Grapow Martin TR

    2012-06-01

    Full Text Available Abstract Background Wire closure still remains the preferred technique despite reasonable disadvantages. Associated complications, such as infection and sternal instability, cause time- and cost-consuming therapies. We present a new tool for sternal closure with its first clinical experience and results. Methods The sternal ZipFixTM System is based on the cable-tie principle. It primarily consists of biocompatible Poly-Ether-Ether-Ketone implants and is predominantly used peristernally through the intercostal space. The system provides a large implant-to-bone contact for better force distribution and for avoiding bone cut through. Results 50 patients were closed with the ZipFixTM system. No sternal instability was observed at 30 days. Two patients developed a mediastinitis that necessitated the removal of the device; however, the ZipFixTM were intact and the sternum remained stable. Conclusions In our initial evaluation, the short-term results have shown that the sternal ZipFixTM can be used safely and effectively. It is fast, easy to use and serves as a potential alternative for traditional wire closure.

  12. Efficacy of a novel strategy for poststernotomy deep sternal infection after thoracic aorta replacement using a prosthetic graft.

    Science.gov (United States)

    Kuriyama, Motone; Yoshida, Yukitaka; Ninomiya, Hitoshi; Yamamoto, Shin; Sasaguri, Shiro; Akita, Shinsuke; Mitsukawa, Nobuyuki

    2018-05-01

    Poststernotomy deep sternal wound infections are persistent and occasionally fatal, especially in cases involving prosthetic grafts, because of their complicated structure and virtual impossibility of removal. We aimed to verify the influence of cooperation with plastic surgeons and our novel strategy for treating deep sternal wound infection after aortic replacement on cardiovascular surgery outcomes. Nine hundred eighty-three consecutive patients were divided into two groups: an early group (2012-2013) and a late group (2014-2015). The late group had received cooperatively improved perioperative wound management: our novel strategy of deep sternal infection based on radical debridement and immediate reconstruction decided by reference to severities of the patient's general condition and widespread infection by early intervention of plastic surgeons. The groups were analysed retrospectively. Binary variables were analysed statistically with the Fisher exact test and continuous variables with the Mann-Whitney U test. Inter-group differences were assessed with the chi-square test. Twenty of 390 cases in the early group and 13 of 593 cases in the late group were associated with deep sternal infection. Morbidity rates of deep sternal wound infection and associated mortality rates 1 year after reconstruction surgery were significantly less (p infection also reduced associated mortality rates. Facilities should consider the early inclusion of plastic surgeons in the treatment of patients undergoing aortic replacement to facilitate better outcomes. Copyright © 2018 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  13. Risk Factors for Complications after Reconstructive Surgery for Sternal Wound Infection

    Directory of Open Access Journals (Sweden)

    Ichiro Hashimoto

    2014-05-01

    Full Text Available Background Although the utility of flaps for the treatment of sternal wound infections following median sternotomy has been reported for 30 years, there have been few reports on the risk factors for complications after reconstruction. The objective of this investigation was to identify factors related to complications after the reconstruction of sternal wound infections. Methods A retrospective analysis of 74 patients with reconstructive surgery after sternal wound infection over a 5-year period was performed. Clinical data including age, sex, body mass index (BMI, comorbidities, bacterial culture, previous cardiac surgery, wound depth, mortality rate, type of reconstructive procedure, and complication rate were collected. Results The patients' BMI ranged from 15.2 to 33.6 kg/m2 (mean, 23.1±3.74 kg/m2. Wound closure complications after reconstructive surgery were observed in 36.5% of the cases. The mortality rate was 2.7%. Diabetes mellitus significantly affected the rate of wound closure complications (P=0.041. A significant difference in the number of complications was seen between Staphylococcus aureus (S. aureus and coagulase-negative Staphylococci (P=0.011. There was a correlation between harvesting of the internal thoracic artery and postoperative complications (P=0.048. The complication rates of the pectoralis major flap, rectus abdominis flap, omentum flap, a combination of pectoralis major flap and rectus abdominis flap, and direct closure were 23.3%, 33.3%, 100%, 37.5%, and 35.7%, respectively. Conclusions Diabetes mellitus, S. aureus, harvesting of the internal thoracic artery, and omentum flap were significant factors for complications after reconstruction. The omentum flap volume may be related to the complications associated with the omentum flap transfer in the present study.

  14. Morphological approach of the sternal foramen: an anatomic study and a short review of the literature.

    Science.gov (United States)

    Gkantsinikoudis, N; Chaniotakis, C; Gkasdaris, G; Georgiou, N; Kapetanakis, S

    2017-01-01

    The sternal foramen (SF) constitutes a specific anatomic defect in sternum, indicating an impaired fusion of ossificated segments, which occurs either in an anatomical part of the sternum or in sternal joints. The aim of this article is to provide baseline statistical data about the variations of the SF, to present a short review of the relevant literature and to compare results with other studies and populations. We review relevant literature, and we present data obtai-ned from skeletal samples of known population and sex. A total of 35 well-preserved dried sterna from the prefecture of Eastern Macedonia and Thrace, Greece, were selected: 20 men and 15 women with a mean age of 55 ± 6 years old. Measurements were made with a sliding calliper and photographic documentation. The incidence of the SF in the 35 dried specimens was 14.2%, 4 men (20% of male sample) and 1 woman (6.6% of female sample) and 80% of sternal foramina were observed in male individuals. The SF was found in the sternum body (2 cases, 40% of foramina), in xiphoid process (2 cases, 40% of foramina) and in sternoxiphoidal junction (1 case, 20% of foramina). All of the sterna presented 1 single visible SF. Two anatomically unique cases were identified throughout these 5 sterna, both belonging in male subjects. The SF constitutes a relatively common variation with great radiological, clinical, and forensic significance. Presence of a SF with irregular bony margins complicates considerably radiological differential diagnosis. Awareness of this important anatomic variation is fundamental for clinicians and autopsy pathologists, in order to avoid severe fatal complications and elucidate the exact cause of death, respectively.

  15. Multicenter Quality Improvement Project to Prevent Sternal Wound Infections in Pediatric Cardiac Surgery Patients.

    Science.gov (United States)

    Woodward, Cathy; Taylor, Richard; Son, Minnette; Taeed, Roozbeh; Jacobs, Marshall L; Kane, Lauren; Jacobs, Jeffrey P; Husain, S Adil

    2017-07-01

    Children undergoing cardiac surgery are at risk for sternal wound infections (SWIs) leading to increased morbidity and mortality. Single-center quality improvement (QI) initiatives have demonstrated decreased infection rates utilizing a bundled approach. This multicenter project was designed to assess the efficacy of a protocolized approach to decrease SWI. Pediatric cardiac programs joined a collaborative effort to prevent SWI. Programs implemented the protocol, collected compliance data, and provided data points from local clinical registries using Society of Thoracic Surgery Congenital Heart Surgery Database harvest-compliant software or from other registries. Nine programs prospectively collected compliance data on 4,198 children. Days between infections were extended from 68.2 days (range: 25-82) to 130 days (range: 43-412). Protocol compliance increased from 76.7% (first quarter) to 91.3% (final quarter). Ninety (1.9%) children developed an SWI preprotocol and 64 (1.5%) postprotocol, P = .18. The 657 (15%) delayed sternal closure patients had a 5% infection rate with 18 (5.7%) in year 1 and 14 (4.3%) in year 2 P = .43. Delayed sternal closure patients demonstrated a trend toward increased risk for SWI of 1.046 for each day the sternum remained open, P = .067. Children who received appropriately timed preop antibiotics developed less infections than those who did not, 1.9% versus 4.1%, P = .007. A multicenter QI project to reduce pediatric SWIs demonstrated an extension of days between infections and a decrease in SWIs. Patients who received preop antibiotics on time had lower SWI rates than those who did not.

  16. Turing mechanism underlying a branching model for lung morphogenesis.

    Science.gov (United States)

    Xu, Hui; Sun, Mingzhu; Zhao, Xin

    2017-01-01

    The mammalian lung develops through branching morphogenesis. Two primary forms of branching, which occur in order, in the lung have been identified: tip bifurcation and side branching. However, the mechanisms of lung branching morphogenesis remain to be explored. In our previous study, a biological mechanism was presented for lung branching pattern formation through a branching model. Here, we provide a mathematical mechanism underlying the branching patterns. By decoupling the branching model, we demonstrated the existence of Turing instability. We performed Turing instability analysis to reveal the mathematical mechanism of the branching patterns. Our simulation results show that the Turing patterns underlying the branching patterns are spot patterns that exhibit high local morphogen concentration. The high local morphogen concentration induces the growth of branching. Furthermore, we found that the sparse spot patterns underlie the tip bifurcation patterns, while the dense spot patterns underlies the side branching patterns. The dispersion relation analysis shows that the Turing wavelength affects the branching structure. As the wavelength decreases, the spot patterns change from sparse to dense, the rate of tip bifurcation decreases and side branching eventually occurs instead. In the process of transformation, there may exists hybrid branching that mixes tip bifurcation and side branching. Since experimental studies have reported that branching mode switching from side branching to tip bifurcation in the lung is under genetic control, our simulation results suggest that genes control the switch of the branching mode by regulating the Turing wavelength. Our results provide a novel insight into and understanding of the formation of branching patterns in the lung and other biological systems.

  17. Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome presenting a primary sternal lesion

    International Nuclear Information System (INIS)

    Serrano, Carlos A.; Leani, Marcelo J.; Rieu, Juan; Serrano, Santiago O.; Dettano, Veronica

    2003-01-01

    SAPHO syndrome-acronym for synovitis, acne, pustules, hyperostosis and osteitis, is a nosological entity including multiple affections with cutaneous and osteoarticular involvement. We report the case of a 59 years old female patient that consulted due to an acute sternal pain. After some months the patient showed a palm-plantar pustular exanthem, acne and fever. SAPHO syndrome was diagnosed based on a CT, an osseous gammagraphy and a biopsy of cutaneous lesions. The current actual tendency is to consider the SAPHO syndrome as a seronegative arthropathy with a similar pathophysiology to Reiter's syndrome. (author)

  18. A new technique for repair of a dislocated sternoclavicular joint using a sternal tension cable system.

    Science.gov (United States)

    Janson, Jacques T; Rossouw, Gawie J

    2013-02-01

    An unstable anterior or posterior sternoclavicular joint dislocation can cause severe morbidity with poor shoulder movement and strength. These dislocations need to be repaired, which can be challenging. Many different procedures have been described to obtain a stable joint fixation with varying results. We report a new technique for repairing a sternoclavicular joint dislocation by using a figure-of-eight sternal cable system. This procedure is relatively simple and reproducible to create a stable and functional sternoclavicular joint. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  19. A global sensitivity analysis approach for morphogenesis models

    NARCIS (Netherlands)

    S.E.M. Boas (Sonja); M.I. Navarro Jimenez (Maria); R.M.H. Merks (Roeland); J.G. Blom (Joke)

    2015-01-01

    textabstract{\\bf Background} %if any Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand the relation between the

  20. Dicer activity in neural crest cells is essential for craniofacial organogenesis and pharyngeal arch artery morphogenesis

    Science.gov (United States)

    Nie, Xuguang; Wang, Qin; Jiao, Kai

    2014-01-01

    MicroRNAs (miRNAs) play important roles in regulating gene expression during numerous biological/pathological processes. Dicer encodes an RNase III endonuclease that is essential for generating most, if not all, functional miRNAs. In this work, we applied a conditional gene inactivation approach to examine the function of Dicer during neural crest cell (NCC) development. Mice with NCC-specific inactivation of Dicer died perinatally. Cranial and cardiac NCC migration into target tissues was not affected by Dicer disruption, but their subsequent development was disturbed. NCC derivatives and their associated mesoderm-derived cells displayed massive apoptosis, leading to severe abnormalities during craniofacial morphogenesis and organogenesis. In addition, the 4th pharyngeal arch artery (PAA) remodeling was affected, resulting in interrupted aortic arch artery type B (IAA-B) in mutant animals. Taken together, our results show that Dicer activity in NCCs is essential for craniofacial development and pharyngeal arch artery morphogenesis. PMID:21256960

  1. An integrated miRNA functional screening and target validation method for organ morphogenesis.

    Science.gov (United States)

    Rebustini, Ivan T; Vlahos, Maryann; Packer, Trevor; Kukuruzinska, Maria A; Maas, Richard L

    2016-03-16

    The relative ease of identifying microRNAs and their increasing recognition as important regulators of organogenesis motivate the development of methods to efficiently assess microRNA function during organ morphogenesis. In this context, embryonic organ explants provide a reliable and reproducible system that recapitulates some of the important early morphogenetic processes during organ development. Here we present a method to target microRNA function in explanted mouse embryonic organs. Our method combines the use of peptide-based nanoparticles to transfect specific microRNA inhibitors or activators into embryonic organ explants, with a microRNA pulldown assay that allows direct identification of microRNA targets. This method provides effective assessment of microRNA function during organ morphogenesis, allows prioritization of multiple microRNAs in parallel for subsequent genetic approaches, and can be applied to a variety of embryonic organs.

  2. Gibberellin influence on the morphogenesis of the moss Bryum argenteum Hedw. in in vitro conditions

    Directory of Open Access Journals (Sweden)

    Sabovljević Aneta

    2010-01-01

    Full Text Available The moss Bryum argenteum Hedw. was treated with gibberellins as well as some inhibitors of gibberellin biosynthesis in order to investigate their influence on B. argenteum morphogenesis. Generally, gibberellins have not been chemically identified in bryophytes, while other groups of classical phytohormones (auxins, cytokinins, abscisic acid and ethylene have been chemically identified in these plants. The in vitro culture of the moss Bryum argenteum was established from sterilized spores. The apical shoots of untreated gametophytes grown in vitro were used to investigate the influence of different substances on secondary protonema and on the growth and multiplication of the gametophytes. B. argenteum reacts differently to the growth regulators applied. Both gibberellins applied in vitro (GA3 and GA7 have a positive effect on B. argenteum morphogenesis. Shoot multiplication was negatively affected by three tested growth retardants (ancymidol, BX-112 and chlorocholine chloride, while these substances did not have such strong effects on the moss protonema development.

  3. Exocrine Gland Morphogenesis: Insights into the Role of Amphiregulin from Development to Disease.

    Science.gov (United States)

    Sisto, Margherita; Lorusso, Loredana; Ingravallo, Giuseppe; Lisi, Sabrina

    2017-12-01

    Amphiregulin (AREG) is a well-characterized member of the epidermal growth factor (EGF) family and is one of the ligands of the EGF receptor (EGFR). AREG plays a key role in mammalian development and in the control of branching morphogenesis in various organs. Furthermore, AREG participates in a wide range of physiological and pathological processes activating the major intracellular signalling cascades governing cell survival, proliferation and motility. In this article, we review current advances in exocrine glands morphogenesis, focusing on the salivary gland, and discuss the essential aspects of AREG structure, function and regulation, and its differential role within the EGFR family of ligands. Finally, we identify emerging aspects in AREG research applied to mammary gland development and the salivary gland autoimmune disease, Sjögren's syndrome.

  4. Acute and subchronic oral toxicity studies in rats of a hydrolyzed chicken sternal cartilage preparation.

    Science.gov (United States)

    Schauss, A G; Merkel, D J; Glaza, S M; Sorenson, S R

    2007-02-01

    Two acute and subchronic oral toxicity studies were conducted in rats to evaluate safety of a patented preparation of hydrolyzed chicken sternal cartilage (BioCell Collagen II) containing collagen type II, chondroitin sulfate, and hyaluronic acid. In the acute oral toxicity study, five males and five females of Sprague-Dawley rats were administered a single dose of 5000 mg of the test product per kg body weight and observed for 14 days. All animals survived and exhibited normal body weight gain throughout the study. Macroscopic necropsy examination conducted on day 15 revealed no gross pathological lesions in any of the animals. In the subchronic study, Sprague-Dawley rats (40 males, 40 females) were divided into four same-sex groups (10 animals/group). Animals in each group were administered daily either 0, 30, 300 or 1000 mg of the test product per kg of body weight for over 90 days. All animals survived and showed no significant changes in their body weights and histopathology. Although some differences were observed between the treated and control animals in several parameters, they were generally not dose-related or considered to be of toxicological significance. In conclusion, the results from the two oral toxicity studies with male and female young adult rats indicated that the test preparation from hydrolyzed chicken sternal cartilage collagen (BioCell Collagen II) was well tolerated at all four doses tested.

  5. A method of experimental rheumatoid arthritis induction using collagen type II isolated from chicken sternal cartilage.

    Science.gov (United States)

    Su, Zhaoliang; Shotorbani, Siamak Sandoghchian; Jiang, Xugan; Ma, Rui; Shen, Huiling; Kong, Fanzhi; Xu, Huaxi

    2013-07-01

    At present, collagen‑induced arthritis (CIA) is the best known and most extensively used model for the immunological and pathological characteristics of human rheumatoid arthritis (RA). This model is useful not only in aiding our understanding of the pathogenesis of this disease, but also in the development of new therapies. Bovine, porcine and human collagen has been used to induce CIA; however, response has been identified to vary between strains and injection conditions, and false positive results and reduced potency are common as a result of minor contaminants or deglycosylated protein. Therefore, in the present study, type II collagen (CII) was isolated and purified from chicken sternal cartilage and was found to successfully induce the RA model. Furthermore, T helper 17 (Th17) cells were observed to infiltrate the joint on day 45 following induction by CII. In vitro, expression of toll‑like receptor 2 (TLR2) increased in peritoneal macrophages stimulated by CII. In addition, blockage of TLR2 was identified to markedly decrease levels of TGF‑β and IL‑6 in the cell culture supernatant. The results indicate that CII isolated from chicken sternal cartilage may be recognized by TLR2 on macrophages, leading to TGF‑β and IL‑6 production and subsequent activation of Th17 cells which mediates CIA development.

  6. FLI-1 Flightless-1 and LET-60 Ras control germ line morphogenesis in C. elegans

    Directory of Open Access Journals (Sweden)

    Dentler William L

    2008-05-01

    Full Text Available Abstract Background In the C. elegans germ line, syncytial germ line nuclei are arranged at the cortex of the germ line as they exit mitosis and enter meiosis, forming a nucleus-free core of germ line cytoplasm called the rachis. Molecular mechanisms of rachis formation and germ line organization are not well understood. Results Mutations in the fli-1 gene disrupt rachis organization without affecting meiotic differentiation, a phenotype in C. elegans referred to here as the germ line morphogenesis (Glm phenotype. In fli-1 mutants, chains of meiotic germ nuclei spanned the rachis and were partially enveloped by invaginations of germ line plasma membrane, similar to nuclei at the cortex. Extensions of the somatic sheath cells that surround the germ line protruded deep inside the rachis and were associated with displaced nuclei in fli-1 mutants. fli-1 encodes a molecule with leucine-rich repeats and gelsolin repeats similar to Drosophila flightless 1 and human Fliih, which have been shown to act as cytoplasmic actin regulators as well as nuclear transcriptional regulators. Mutations in let-60 Ras, previously implicated in germ line development, were found to cause the Glm phenotype. Constitutively-active LET-60 partially rescued the fli-1 Glm phenotype, suggesting that LET-60 Ras and FLI-1 might act together to control germ line morphogenesis. Conclusion FLI-1 controls germ line morphogenesis and rachis organization, a process about which little is known at the molecular level. The LET-60 Ras GTPase might act with FLI-1 to control germ line morphogenesis.

  7. Major bleeding during negative pressure wound/VAC (R) - therapy for postsurgical deep sternal wound infection - a critical appraisal

    NARCIS (Netherlands)

    van Wingerden, J.J.; Segers, P.; Jekel, L.

    2011-01-01

    Negative-pressure wound therapy, commercially known as vacuum-assisted closure (V.A.C.(R)) therapy, has become one of the most popular (and efficacious) interim (prior to flap reconstruction) or definite methods of managing deep sternal wound infection. Complications such as profuse bleeding, which

  8. Spermine modulates fungal morphogenesis and activates plasma membrane H+-ATPase during yeast to hyphae transition

    Directory of Open Access Journals (Sweden)

    Antônio Jesus Dorighetto Cogo

    2018-02-01

    Full Text Available Polyamines play a regulatory role in eukaryotic cell growth and morphogenesis. Despite many molecular advances, the underlying mechanism of action remains unclear. Here, we investigate a mechanism by which spermine affects the morphogenesis of a dimorphic fungal model of emerging relevance in plant interactions, Yarrowia lipolytica, through the recruitment of a phytohormone-like pathway involving activation of the plasma membrane P-type H+-ATPase. Morphological transition was followed microscopically, and the H+-ATPase activity was analyzed in isolated membrane vesicles. Proton flux and acidification were directly probed at living cell surfaces by a non-invasive selective ion electrode technique. Spermine and indol-3-acetic acid (IAA induced the yeast-hypha transition, influencing the colony architecture. Spermine induced H+-ATPase activity and H+ efflux in living cells correlating with yeast-hypha dynamics. Pharmacological inhibition of spermine and IAA pathways prevented the physio-morphological responses, and indicated that spermine could act upstream of the IAA pathway. This study provides the first compelling evidence on the fungal morphogenesis and colony development as modulated by a spermine-induced acid growth mechanism analogous to that previously postulated for the multicellular growth regulation of plants.

  9. PAR-Complex and Crumbs Function During Photoreceptor Morphogenesis and Retinal Degeneration.

    Science.gov (United States)

    Pichaud, Franck

    2018-01-01

    The fly photoreceptor has long been used as a model to study sensory neuron morphogenesis and retinal degeneration. In particular, elucidating how these cells are built continues to help further our understanding of the mechanisms of polarized cell morphogenesis, intracellular trafficking and the causes of human retinal pathologies. The conserved PAR complex, which in flies consists of Cdc42-PAR6-aPKC-Bazooka, and the transmembrane protein Crumbs (Crb) are key players during photoreceptor morphogenesis. While the PAR complex regulates polarity in many cell types, Crb function in polarity is relatively specific to epithelial cells. Together Cdc42-PAR6-aPKC-Bazooka and Crb orchestrate the differentiation of the photoreceptor apical membrane (AM) and zonula adherens (ZA) , thus allowing these cells to assemble into a neuro-epithelial lattice. In addition to its function in epithelial polarity, Crb has also been shown to protect fly photoreceptors from light-induced degeneration, a process linked to Rhodopsin expression and trafficking. Remarkably, mutations in the human Crumbs1 (CRB1) gene lead to retinal degeneration, making the fly photoreceptor a powerful disease model system.

  10. PAR-Complex and Crumbs Function During Photoreceptor Morphogenesis and Retinal Degeneration

    Directory of Open Access Journals (Sweden)

    Franck Pichaud

    2018-03-01

    Full Text Available The fly photoreceptor has long been used as a model to study sensory neuron morphogenesis and retinal degeneration. In particular, elucidating how these cells are built continues to help further our understanding of the mechanisms of polarized cell morphogenesis, intracellular trafficking and the causes of human retinal pathologies. The conserved PAR complex, which in flies consists of Cdc42-PAR6-aPKC-Bazooka, and the transmembrane protein Crumbs (Crb are key players during photoreceptor morphogenesis. While the PAR complex regulates polarity in many cell types, Crb function in polarity is relatively specific to epithelial cells. Together Cdc42-PAR6-aPKC-Bazooka and Crb orchestrate the differentiation of the photoreceptor apical membrane (AM and zonula adherens (ZA, thus allowing these cells to assemble into a neuro-epithelial lattice. In addition to its function in epithelial polarity, Crb has also been shown to protect fly photoreceptors from light-induced degeneration, a process linked to Rhodopsin expression and trafficking. Remarkably, mutations in the human Crumbs1 (CRB1 gene lead to retinal degeneration, making the fly photoreceptor a powerful disease model system.

  11. A novel tantalum-containing bioglass. Part II. Development of a bioadhesive for sternal fixation and repair

    Energy Technology Data Exchange (ETDEWEB)

    Alhalawani, Adel MF. [Department of Mechanical & Industrial Engineering, Ryerson University, Toronto, Ontario (Canada); Li Ka Shing Knowledge Institute, St. Michael' s Hospital, Toronto, Ontario, Canada. (Canada); Mehrvar, Cina [Department of Mechanical & Industrial Engineering, Ryerson University, Toronto, Ontario (Canada); Stone, Wendy [Department of Chemistry and Biology, Ryerson University, Toronto, Ontario (Canada); Waldman, Stephen D. [Li Ka Shing Knowledge Institute, St. Michael' s Hospital, Toronto, Ontario, Canada. (Canada); Department of Chemical Engineering, Ryerson University, Toronto, Ontario (Canada); Towler, Mark R., E-mail: mtowler@ryerson.ca [Department of Mechanical & Industrial Engineering, Ryerson University, Toronto, Ontario (Canada); Li Ka Shing Knowledge Institute, St. Michael' s Hospital, Toronto, Ontario, Canada. (Canada)

    2017-02-01

    With over a million median sternotomy surgeries performed worldwide every year, sternal wound complications have posed a serious risk to the affected patients. A rigid therapeutic sternal fixation device has therefore become a necessity. In this work, the incorporation of up to 0.5 mol% of tantalum pentoxide (Ta{sub 2}O{sub 5}), in exchange for zinc oxide (ZnO), into the SiO{sub 2}-ZnO-CaO-SrO-P{sub 2}O{sub 5} glass system is presented. The effect of Ta incorporation on the physical, chemical and biological properties of the glass polyalkenoate cements (GPCs) prepared from them have been presented in this manuscript. The data obtained have confirmed that Ta{sub 2}O{sub 5} incorporation into the reference glass system results in increased working times, radiopacity, ion solubility, and long-term mechanical stability. The formulated glass systems have also shown clear antibacterial and antifungal activity against both Gram-negative (Escherichia coli) and Gram-positive prokaryotes (Staphylococcus aureus and Streptococcus epidermidis), as well as eukaryotes (Fusarium solani). Cytotoxicity testing showed that Ta incorporation results in no toxicity effect and may simulate osseo-integration when tested in animal models. These new metallic-containing biomaterial adhesives have been developed for sternal fixation and repair. As a permanent implant, the formulated adhesives can be used in conjunction with sternal cable ties to offer optimal fixation for patients and reduce post-operative complications such as bacterial infection and pain from micro-motion. - Highlights: • Novel cements based on a tantalum-containing ionomer glass are presented. • The cements resulted in increased working times and long-term mechanical stability. • The cements exhibited both antibiotic and antimycotic activity. • The cements tested did not display any cytotoxic effects. • These cements have potential for sternal fixation and repair.

  12. Management of sternal precautions following median sternotomy by physical therapists in Australia: a web-based survey.

    Science.gov (United States)

    Tuyl, Lara J; Mackney, Jennifer H; Johnston, Catherine L

    2012-01-01

    Sternal precautions are utilized within many hospitals with the aim of preventing the occurrence of sternal complications (eg, infection, wound breakdown) following midline sternotomy. The evidence base for sternal precaution protocols, however, has been questioned due to a paucity of research, unknown effect on patient outcomes, and possible discrepancies in pattern of use among institutions. The objective of this study was to investigate and document the use of sternal precautions by physical therapists in the treatment of patients following median sternotomy in hospitals throughout Australia, from immediately postsurgery to discharge from the hospital. A cross-sectional, observational design was used. An anonymous, Web-based survey was custom designed for use in the study. The questionnaire was content validated, and the online functionality was assessed. The senior cardiothoracic physical therapist from each hospital identified as currently performing cardiothoracic surgery (N=51) was invited to participate. The response rate was 58.8% (n=30). Both public (n=18) and private (n=12) hospitals in all states of Australia were represented. Management protocols reported by participants included wound support (n=22), restrictions on lifting and transfers (n=23), and restrictions on mobility aid use (n=15). Factors influencing clinical practice most commonly included "workplace practices/protocols" (n=27) and "clinical experience" (n=22). Limitations The study may be limited by response bias. Significant variation exists in the sternal precautions and protocols used in the treatment of patients following median sternotomy in Australian hospitals. Further research is needed to investigate whether the restrictions and precautions used are necessary and whether protocols have an impact on patient outcomes, including rates of recovery and length of stay.

  13. The history of the management of sternal osteomyelitis and mediastinitis - from Hippocrates until today.

    Science.gov (United States)

    Ennker, Ina Carolin; Ennker, Jürgen C

    2014-01-01

    Even during the time of Hippocrates, Galen and their colleagues recognized mediastinal affections. However, they were not considered with the surgical treatment. First progress in the treatment options of this severe disease, still denoted as 'terra incognita', over to today's gold standard are pictured. The mediastinitis-registry which was founded by the German Society for Thoracic and Cardiovascular Surgery (DGTHG) in 2011 and the recent establishment of the study group to adopt a guideline 'diagnosis and therapy of postoperative mediastinitis/sternal osteomyelitis following cardiac surgery' are attempts to a standardization of the treatment. Substantial advancement in the treatment of postoperative mediastinitis could be achieved in the past. The mortality dropped as low as less than 10%. With these implementations more benefit for the patients' outcome can be expected.

  14. The history of the management of sternal osteomyelitis and mediastinitis – from Hippocrates until today

    Directory of Open Access Journals (Sweden)

    Ennker, Ina Carolin

    2014-06-01

    Full Text Available Even during the time of Hippocrates, Galen and their colleagues recognized mediastinal affections. However, they were not considered with the surgical treatment. First progress in the treatment options of this severe disease, still denoted as ‘terra incognita’, over to today’s gold standard are pictured.The mediastinitis-registry which was founded by the German Society for Thoracic and Cardiovascular Surgery (DGTHG in 2011 and the recent establishment of the study group to adopt a guideline ‘diagnosis and therapy of postoperative mediastinitis/sternal osteomyelitis following cardiac surgery’ are attempts to a standardization of the treatment. Substantial advancement in the treatment of postoperative mediastinitis could be achieved in the past. The mortality dropped as low as less than 10%. With these implementations more benefit for the patients’ outcome can be expected.

  15. The history of the management of sternal osteomyelitis and mediastinitis – from Hippocrates until today

    Science.gov (United States)

    Ennker, Ina Carolin; Ennker, Jürgen C.

    2014-01-01

    Even during the time of Hippocrates, Galen and their colleagues recognized mediastinal affections. However, they were not considered with the surgical treatment. First progress in the treatment options of this severe disease, still denoted as ‘terra incognita’, over to today’s gold standard are pictured. The mediastinitis-registry which was founded by the German Society for Thoracic and Cardiovascular Surgery (DGTHG) in 2011 and the recent establishment of the study group to adopt a guideline ‘diagnosis and therapy of postoperative mediastinitis/sternal osteomyelitis following cardiac surgery’ are attempts to a standardization of the treatment. Substantial advancement in the treatment of postoperative mediastinitis could be achieved in the past. The mortality dropped as low as less than 10%. With these implementations more benefit for the patients’ outcome can be expected. PMID:26504718

  16. Treatment of gram-positive deep sternal wound infections in cardiac surgery -experiences with daptomycin-

    Directory of Open Access Journals (Sweden)

    Coskun Kasim O

    2011-09-01

    Full Text Available Abstract The reported incidence of deep sternal wound infection (DSWI after cardiac surgery is 0.4-5% with Staphylococcus aureus being the most common pathogen isolated from infected wound sternotomies and bacteraemic blood cultures. This infection is associated with a higher morbidity and mortality than other known aetiologies. Little is reported about the optimal antibiotic management. The aim of the study is to quantify the application of daptomycin treatment of DSWI due to gram-positive organisms post cardiac surgery. We performed an observational analysis in 23 cases of post sternotomy DSWI with gram-positive organisms February 2009 and September 2010. When the wound appeared viable and the microbiological cultures were negative, the technique of chest closure was individualised to the patient. The incidence of DSWI was 1.46%. The mean dose of daptomycin application was 4.4 ± 0.9 mg/kg/d and the average duration of the daptomycin application was 14.47 ± 7.33 days. In 89% of the patients VAC therapy was used. The duration from daptomycin application to sternal closure was 18 ± 13.9 days. The parameters of infection including, fibrinogen (p = 0.03, white blood cell count (p = 0.001 and C-reactive protein (p = 0.0001 were significantly reduced after daptomycin application. We had no mortality and wound healing was successfully achieved in all patients. Treatment of DSWI due to gram-positive organisms with a daptomycin-containing antibiotic regimen is safe, effective and promotes immediate improvement of local wound conditions. Based on these observations, daptomycin may offer a new treatment option for expediting surgical management of DSWI after cardiac surgery.

  17. Emergent properties during dorsal closure in Drosophila morphogenesis

    International Nuclear Information System (INIS)

    Peralta, X G; Toyama, Y; Edwards, G S; Kiehart, D P

    2008-01-01

    Dorsal closure is an essential stage of Drosophila development that is a model system for research in morphogenesis and biological physics. Dorsal closure involves an orchestrated interplay between gene expression and cell activities that produce shape changes, exert forces and mediate tissue dynamics. We investigate the dynamics of dorsal closure based on confocal microscopic measurements of cell shortening in living embryos. During the mid-stages of dorsal closure we find that there are fluctuations in the width of the leading edge cells but the time-averaged analysis of measurements indicate that there is essentially no net shortening of cells in the bulk of the leading edge, that contraction predominantly occurs at the canthi as part of the process for zipping together the two leading edges of epidermis and that the rate constant for zipping correlates with the rate of movement of the leading edges. We characterize emergent properties that regulate dorsal closure, i.e., a velocity governor and the coordination and synchronization of tissue dynamics

  18. Heart morphogenesis gene regulatory networks revealed by temporal expression analysis.

    Science.gov (United States)

    Hill, Jonathon T; Demarest, Bradley; Gorsi, Bushra; Smith, Megan; Yost, H Joseph

    2017-10-01

    During embryogenesis the heart forms as a linear tube that then undergoes multiple simultaneous morphogenetic events to obtain its mature shape. To understand the gene regulatory networks (GRNs) driving this phase of heart development, during which many congenital heart disease malformations likely arise, we conducted an RNA-seq timecourse in zebrafish from 30 hpf to 72 hpf and identified 5861 genes with altered expression. We clustered the genes by temporal expression pattern, identified transcription factor binding motifs enriched in each cluster, and generated a model GRN for the major gene batteries in heart morphogenesis. This approach predicted hundreds of regulatory interactions and found batteries enriched in specific cell and tissue types, indicating that the approach can be used to narrow the search for novel genetic markers and regulatory interactions. Subsequent analyses confirmed the GRN using two mutants, Tbx5 and nkx2-5 , and identified sets of duplicated zebrafish genes that do not show temporal subfunctionalization. This dataset provides an essential resource for future studies on the genetic/epigenetic pathways implicated in congenital heart defects and the mechanisms of cardiac transcriptional regulation. © 2017. Published by The Company of Biologists Ltd.

  19. Mis-expression of grainyhead-like transcription factors in zebrafish leads to defects in enveloping layer (EVL) integrity, cellular morphogenesis and axial extension.

    Science.gov (United States)

    Miles, Lee B; Darido, Charbel; Kaslin, Jan; Heath, Joan K; Jane, Stephen M; Dworkin, Sebastian

    2017-12-14

    The grainyhead-like (grhl) transcription factors play crucial roles in craniofacial development, epithelial morphogenesis, neural tube closure, and dorso-ventral patterning. By utilising the zebrafish to differentially regulate expression of family members grhl2b and grhl3, we show that both genes regulate epithelial migration, particularly convergence-extension (CE) type movements, during embryogenesis. Genetic deletion of grhl3 via CRISPR/Cas9 results in failure to complete epiboly and pre-gastrulation embryonic rupture, whereas morpholino (MO)-mediated knockdown of grhl3 signalling leads to aberrant neural tube morphogenesis at the midbrain-hindbrain boundary (MHB), a phenotype likely due to a compromised overlying enveloping layer (EVL). Further disruptions of grhl3-dependent pathways (through co-knockdown of grhl3 with target genes spec1 and arhgef19) confirm significant MHB morphogenesis and neural tube closure defects. Concomitant MO-mediated disruption of both grhl2b and grhl3 results in further extensive CE-like defects in body patterning, notochord and somite morphogenesis. Interestingly, over-expression of either grhl2b or grhl3 also leads to numerous phenotypes consistent with disrupted cellular migration during gastrulation, including embryo dorsalisation, axial duplication and impaired neural tube migration leading to cyclopia. Taken together, our study ascribes novel roles to the Grhl family in the context of embryonic development and morphogenesis.

  20. Modulating Wnt Signaling Rescues Palate Morphogenesis in Pax9 Mutant Mice.

    Science.gov (United States)

    Li, C; Lan, Y; Krumlauf, R; Jiang, R

    2017-10-01

    Cleft palate is a common birth defect caused by disruption of palatogenesis during embryonic development. Although mutations disrupting components of the Wnt signaling pathway have been associated with cleft lip and palate in humans and mice, the mechanisms involving canonical Wnt signaling and its regulation in secondary palate development are not well understood. Here, we report that canonical Wnt signaling plays an important role in Pax9-mediated regulation of secondary palate development. We found that cleft palate pathogenesis in Pax9-deficient embryos is accompanied by significantly reduced expression of Axin2, an endogenous target of canonical Wnt signaling, in the developing palatal mesenchyme, particularly in the posterior regions of the palatal shelves. We found that expression of Dkk2, encoding a secreted Wnt antagonist, is significantly increased whereas the levels of active β-catenin protein, the essential transcriptional coactivator of canonical Wnt signaling, is significantly decreased in the posterior regions of the palatal shelves in embryonic day 13.5 Pax9-deficent embryos in comparison with control littermates. We show that small molecule-mediated inhibition of Dickkopf (DKK) activity in utero during palatal shelf morphogenesis partly rescued secondary palate development in Pax9-deficient embryos. Moreover, we found that genetic inactivation of Wise, which is expressed in the developing palatal shelves and encodes another secreted antagonist of canonical Wnt signaling, also rescued palate morphogenesis in Pax9-deficient mice. Furthermore, whereas Pax9 del/del embryos exhibit defects in palatal shelf elevation/reorientation and significant reduction in accumulation of hyaluronic acid-a high molecular extracellular matrix glycosaminoglycan implicated in playing an important role in palatal shelf elevation-80% of Pax9 del/del ;Wise -/- double-mutant mouse embryos exhibit rescued palatal shelf elevation/reorientation, accompanied by restored

  1. Coupling gene expression and multicellular morphogenesis during fruiting body formation in Myxococcus xanthus

    DEFF Research Database (Denmark)

    Søgaard-Andersen, L.; Overgaard, M.; Lobedanz, S.

    2003-01-01

    xanthus illustrates this coupling in the construction of a multicellular structure. Fruiting body formation involves two stages: aggregation of cells into mounds and the position-specific sporulation of cells that have accumulated inside mounds. Developmental gene expression propels these two processes...... morphogenesis. Accumulation of the C-signal is tightly regulated and involves transcriptional activation of the csgA gene and proteolysis of the full-length CsgA protein to produce the shorter cell surface-associated 17 kDa C-signal protein. The C-signal induces aggregation, sporulation and developmental gene...

  2. Complex interactions between GSK3 and aPKC in Drosophila embryonic epithelial morphogenesis.

    Directory of Open Access Journals (Sweden)

    Nicole A Kaplan

    Full Text Available Generally, epithelial cells must organize in three dimensions to form functional tissue sheets. Here we investigate one such sheet, the Drosophila embryonic epidermis, and the morphogenetic processes organizing cells within it. We report that epidermal morphogenesis requires the proper distribution of the apical polarity determinant aPKC. Specifically, we find roles for the kinases GSK3 and aPKC in cellular alignment, asymmetric protein distribution, and adhesion during the development of this polarized tissue. Finally, we propose a model explaining how regulation of aPKC protein levels can reorganize both adhesion and the cytoskeleton.

  3. Morphogenesis of the infectious HIV-1 virion

    Directory of Open Access Journals (Sweden)

    Jun-Ichi eSakuragi

    2011-12-01

    Full Text Available The virion of HIV-1 is spherical and viral glycoprotein spikes (gp120, gp41 protrude from its envelope. The characteristic cone-shaped core exists within the virion, caging the ribonucleoprotein (RNP complex, which is comprised of viral RNA, nucleocapsid (NC and viral enzymes. The HIV-1 virion is budded and released from the infected cell as an immature donut-shaped particle. During or immediately after release, viral protease (PR is activated and subsequently processes the viral structural protein Gag. Through this maturation process, virions acquire infectivity, but its mechanism and transition of morphology largely remain unclear. Recent technological advances in experimental devices and techniques have made it possible to closely dissect the viral production site on the cell, the exterior – or even the interior – of an individual virion, and many new aspects on virion morphology and maturation. In this manuscript, I review the morphogenesis of HIV-1 virions. I focus on several studies, including some of our recent findings, which examined virion formation and/or maturation processes. The story of novel compound, which inhibits virion maturation, and the importance of maturation research are also discussed.

  4. Mechanical growth and morphogenesis of seashells

    KAUST Repository

    Moulton, D.E.

    2012-10-01

    Seashells grow through the local deposition of mass along the aperture. Many mathematical descriptions of the shapes of shells have been provided over the years, and the basic logarithmic coiling seen in mollusks can be simulated with few parameters. However, the developmental mechanisms underlying shell coiling are largely not understood and the ubiquitous presence of ornamentation such as ribs, tubercles, or spines presents yet another level of difficulty. Here we develop a general model for shell growth based entirely on the local geometry and mechanics of the aperture and mantle. This local description enables us to efficiently describe both arbitrary growth velocities and the evolution of the shell aperture itself. We demonstrate how most shells can be simulated within this framework. We then turn to the mechanics underlying the shell morphogenesis, and develop models for the evolution of the aperture. We demonstrate that the elastic response of the mantle during shell deposition provides a natural mechanism for the formation of three-dimensional ornamentation in shells. © 2012 Elsevier Ltd.

  5. Multiscale information modelling for heart morphogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Abdulla, T; Imms, R; Summers, R [Department of Electronic and Electrical Engineering, Loughborough University, Loughborough (United Kingdom); Schleich, J M, E-mail: T.Abdulla@lboro.ac.u [LTSI Signal and Image Processing Laboratory, University of Rennes 1, Rennes (France)

    2010-07-01

    Science is made feasible by the adoption of common systems of units. As research has become more data intensive, especially in the biomedical domain, it requires the adoption of a common system of information models, to make explicit the relationship between one set of data and another, regardless of format. This is being realised through the OBO Foundry to develop a suite of reference ontologies, and NCBO Bioportal to provide services to integrate biomedical resources and functionality to visualise and create mappings between ontology terms. Biomedical experts tend to be focused at one level of spatial scale, be it biochemistry, cell biology, or anatomy. Likewise, the ontologies they use tend to be focused at a particular level of scale. There is increasing interest in a multiscale systems approach, which attempts to integrate between different levels of scale to gain understanding of emergent effects. This is a return to physiological medicine with a computational emphasis, exemplified by the worldwide Physiome initiative, and the European Union funded Network of Excellence in the Virtual Physiological Human. However, little work has been done on how information modelling itself may be tailored to a multiscale systems approach. We demonstrate how this can be done for the complex process of heart morphogenesis, which requires multiscale understanding in both time and spatial domains. Such an effort enables the integration of multiscale metrology.

  6. Multiscale information modelling for heart morphogenesis

    International Nuclear Information System (INIS)

    Abdulla, T; Imms, R; Summers, R; Schleich, J M

    2010-01-01

    Science is made feasible by the adoption of common systems of units. As research has become more data intensive, especially in the biomedical domain, it requires the adoption of a common system of information models, to make explicit the relationship between one set of data and another, regardless of format. This is being realised through the OBO Foundry to develop a suite of reference ontologies, and NCBO Bioportal to provide services to integrate biomedical resources and functionality to visualise and create mappings between ontology terms. Biomedical experts tend to be focused at one level of spatial scale, be it biochemistry, cell biology, or anatomy. Likewise, the ontologies they use tend to be focused at a particular level of scale. There is increasing interest in a multiscale systems approach, which attempts to integrate between different levels of scale to gain understanding of emergent effects. This is a return to physiological medicine with a computational emphasis, exemplified by the worldwide Physiome initiative, and the European Union funded Network of Excellence in the Virtual Physiological Human. However, little work has been done on how information modelling itself may be tailored to a multiscale systems approach. We demonstrate how this can be done for the complex process of heart morphogenesis, which requires multiscale understanding in both time and spatial domains. Such an effort enables the integration of multiscale metrology.

  7. Anatomic study of the vascular perfusion of the sternum and its clinical relevance in deep sternal wound infection

    Directory of Open Access Journals (Sweden)

    Spindler, Nick

    2017-06-01

    Full Text Available Introduction: Deep sternal wound infections (DSWI are a rare but devastating complication after median sternotomy. Minor perfusion in bone and soft tissue, especially after recruiting the internal mammary artery for bypass supports the development of wound infection and nonunion of the sternal bone. The aim of the study was the macroscopic and radiological presentation of the vascular system supplying the sternum, in particular the compensating blood supply routes in the event that the internal mammary artery is no longer available after use as a bypass vessel.Method: This anatomic study was carried out on the anterior chest wall of 7 specimens. The thorax plates of 7 specimens were analyzed macroscopically after microsurgical preparation. Different anatomic preparations were produced using different contrast or form-giving substances. Radiological analysis and three-dimensional reconstructions were performed to show alternative, collateral sternal vessel perfusion under estimation of the loss of the internal thoracic artery due to a bypass.Results: The length of the ITA (internal thoracic artery, measured from the beginning of the first rib to the division into the superior epigastric artery and musculophrenic artery, was an average of 16.3 cm. On average, 18.5 branches were delivered from each artery, 10 medially to the sternum supply, and the intercostal muscle. Conclusion: Our analysis gives an overview of the macroanatomic vessel system supplying the sternal bone, describing especially a common trunk deriving from the ITA and supplying multiple branches and playing an important role in building a collateral circulation of the sternum.For better evaluation, in vivo CT analysis with contrast media should be performed in patients prior to the operation and directly after the use of the double ITA to demonstrate the change in perfusion of the sternum.In the future, preconditioning of the sternum by coiling the deriving branches could become an

  8. Results of Three-Dimensional Conformal Radiation Therapy for the Treatment of a Solitary Sternal Relapse of Breast Cancer

    International Nuclear Information System (INIS)

    Kim, Hae Young; Huh, Seung Jae; Park, Won; Choi, Do Ho; Kang, Min Kyu; Yang, Jung Hyun; Nam, Seok Jin; Im, Young Hyuck

    2008-01-01

    To evaluate the response and survival rate after three-dimensional conformal radiation therapy (3D-CRT) of patients with a solitary sternal relapse of breast cancer. Seventeen patients between May 1996 and June 2005 were evaluated with the salvage 3D-CRT treatment of a solitary sternal relapse of breast cancer. The treatment fields included the gross tumor volume with 2 cm margins. The total radiation dose was 35.0 ∼61.5 Gy (biologic effective dose of 43.7 ∼76.9 Gy10 using an α/β ratio of 10 Gy), with a daily dose of 1.8∼3.0 Gy. The tumor response was evaluated by the change in maximum tumor size via follow up CT scans 1∼3 months after the completion of treatment. An objective tumor response was achieved in all patients, with a complete response in 5 patients and a partial response in 12 patients. The 5-year overall survival rate was 51.9% (median survival time: 27 months), and the most important factor affecting overall survival was the disease-free interval (interval from primary surgery of breast cancer to the development of sternal metastasis): The 5-year overall survival rate was 61.8% for patients with a disease-free interval ≥12 months and 0.0% for patients < with disease-free interval <12 months (p=0.03). The response to 3D-CRT was good in patients with solitary sternal relapse of breast cancer. Particularly, patients with long disease-free interval from primary surgery survived significantly longer than patients with short disease-free interval from primary surgery

  9. Management plan for deep sternal wound infection targeting to survival free of recurrence: A prospective evaluation study

    Directory of Open Access Journals (Sweden)

    Ibrahim Kasb

    2016-10-01

    Conclusion: Management of DSWI is tedious, has prolonged hospital stay and is associated with high morbidity and mortality rates. Management of DSWI must be personalized according to findings on exploration of the sternal wound and flap coverage must be initiated only when the patient is bacteriologically free. Both PMF and/or VOF provided high acceptable success rate defined as survival free of DSWI recurrence.

  10. A protocadherin-cadherin-FLRT3 complex controls cell adhesion and morphogenesis.

    Directory of Open Access Journals (Sweden)

    Xuejun Chen

    2009-12-01

    Full Text Available Paraxial protocadherin (PAPC and fibronectin leucine-rich domain transmembrane protein-3 (FLRT3 are induced by TGFbeta signaling in Xenopus embryos and both regulate morphogenesis by inhibiting C-cadherin mediated cell adhesion.We have investigated the functional and physical relationships between PAPC, FLRT3, and C-cadherin. Although neither PAPC nor FLRT3 are required for each other to regulate C-cadherin adhesion, they do interact functionally and physically, and they form a complex with cadherins. By itself PAPC reduces cell adhesion physiologically to induce cell sorting, while FLRT3 disrupts adhesion excessively to cause cell dissociation. However, when expressed together PAPC limits the cell dissociating and tissue disrupting activity of FLRT3 to make it effective in physiological cell sorting. PAPC counteracts FLRT3 function by inhibiting the recruitment of the GTPase RND1 to the FLRT3 cytoplasmic domain.PAPC and FLRT3 form a functional complex with cadherins and PAPC functions as a molecular "governor" to maintain FLRT3 activity at the optimal level for physiological regulation of C-cadherin adhesion, cell sorting, and morphogenesis.

  11. The use of antibiotic-impregnated cement beads in the management of sternal osteomyelitis after treatment for malignant lymphoma

    International Nuclear Information System (INIS)

    Nakabayashi, Yohei; Kikuchi, Noriaki; Ogino, Toshihiko; Kim, Cholsu; Miyazaki, Ryouta; Sadahiro, Mitsuaki

    2010-01-01

    Currently, the majority of patients who develop Hodgkin's disease can be cured with radiotherapy and/or chemotherapy. A long follow up of cured patients has shown that the cumulative toxicity from treatment related complication rivals the mortality from Hodgkin's disease. We present a 38-year old male with Hodgkin's disease, treated with radiation and chemotherapy, who developed cardiac infarction and severe mediastinal fibrosis. After median sternotomy for cardiac bypass operation, he suffered from sternal osteitis and superior mediastinitis. A radical debridement must be avoided to protect the bypassed conduit embedded in the extended severe mediastinal fibrosis. Then after appropriate debridement and management of methicillin-resistant Staphylococcus aureus (MRSA) infection, latissimus dorsi myocutaneous flap transfer and use of vancomycin-impregnated cement beads achieved infection control. In this study we present our experience with bibliographical discussion. With the concept presented in this study, however, a consistent cure and prevention from subsequent infection-related morbidity and mortality were achieved even in the subset of the most severe, recalcitrant cases of sternal osteitis, and with an unacceptable rate of complications. This justifies the invasive nature of the procedure and suggests its application not only as a salvage operation for failures after previous interventions, but also as a primary approach for severe sternal osteomyelitis. (author)

  12. hmmr mediates anterior neural tube closure and morphogenesis in the frog Xenopus.

    Science.gov (United States)

    Prager, Angela; Hagenlocher, Cathrin; Ott, Tim; Schambony, Alexandra; Feistel, Kerstin

    2017-10-01

    Development of the central nervous system requires orchestration of morphogenetic processes which drive elevation and apposition of the neural folds and their fusion into a neural tube. The newly formed tube gives rise to the brain in anterior regions and continues to develop into the spinal cord posteriorly. Conspicuous differences between the anterior and posterior neural tube become visible already during neural tube closure (NTC). Planar cell polarity (PCP)-mediated convergent extension (CE) movements are restricted to the posterior neural plate, i.e. hindbrain and spinal cord, where they propagate neural fold apposition. The lack of CE in the anterior neural plate correlates with a much slower mode of neural fold apposition anteriorly. The morphogenetic processes driving anterior NTC have not been addressed in detail. Here, we report a novel role for the breast cancer susceptibility gene and microtubule (MT) binding protein Hmmr (Hyaluronan-mediated motility receptor, RHAMM) in anterior neurulation and forebrain development in Xenopus laevis. Loss of hmmr function resulted in a lack of telencephalic hemisphere separation, arising from defective roof plate formation, which in turn was caused by impaired neural tissue narrowing. hmmr regulated polarization of neural cells, a function which was dependent on the MT binding domains. hmmr cooperated with the core PCP component vangl2 in regulating cell polarity and neural morphogenesis. Disrupted cell polarization and elongation in hmmr and vangl2 morphants prevented radial intercalation (RI), a cell behavior essential for neural morphogenesis. Our results pinpoint a novel role of hmmr in anterior neural development and support the notion that RI is a major driving force for anterior neurulation and forebrain morphogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Experience with Vacuum-assisted closure of sternal wound infections following cardiac surgery and evaluation of chronic complications associated with its use.

    Science.gov (United States)

    Bapat, Vinayak; El-Muttardi, Naguib; Young, Christopher; Venn, Graham; Roxburgh, James

    2008-01-01

    We report our experience in use of Vacuum-assisted closure therapy (VAC) in the treatment of poststernotomy wound infection with emphasis on recurrent wound-related problems after use of VAC and their treatment. Between July 2000 and June 2003, 2706 patients underwent various cardiac procedures via median sternotomy. Forty-nine patients with postoperative sternal wound infection (1.9%) were managed with VAC. Wounds were classified as either superficial sternal wound infection (28 patients) or deep sternal wound infection (21 patients). In the superficial sternal wound infection group, 23 patients had VAC as definitive treatment (GroupA), while five patients (Group B) had VAC followed by surgical closure. Similarly, in the deep sternal wound infection group, 12 patients had VAC as definitive treatment (Group C), while nine patients had VAC followed by surgical closure (Group D). Patients were discharged after satisfactory wound closure. Upon discharge patients were followed up at interval of three to six months. Recurrent sternal problems when identified were investigated and additional surgical procedures were carried out when necessary. There were nine deaths, all due to unrelated causes except in one patient who died of right ventricular rupture (Group C). Nine patients in Group A had recurrent wound problems of which six had VAC system for > 21 days. Three patients underwent extensive debridement due to sternal osteomyelitis. All eight patients in Group B presented with chronic wound-related problems and underwent multiple debridements. Four patients had laparoscopic omental flaps. In contrast 14 patients (Group B and D) who were treated with shorter duration of VAC followed by either a flap or direct surgical closure, did not present with recurrent problems. VAC therapy is a safe and reliable option in the treatment of sternal wound infection. However, prolonged use of VAC system as a replacement for surgical closure of sternal wound appears to be associated

  14. Effect of the degree of sternal depression on the cardiac rotation in pectus excavatum: evaluation with spiral CT

    International Nuclear Information System (INIS)

    Yu Jianqun; Yang Zhigang; Li Zhenlin; Guo Yingkun; Lu Chunyan; Zhang Mei

    2004-01-01

    Objective: To evaluate the effects of the degree of sternal depression on the cardiac rotation in pectus excavatum by using spiral CT. Methods: Spiral CT features of 32 patients with surgically corrected pectus excavatum were retrospectively reviewed. They included 27 males and 5 females ranging in age from 6 months to 17 years (mean, 6.3 years). Analysis was based on relationship among the degree of sternal depression, CT depression index, cardiac rotation angle, and PV angle. Results: 32 cases of pectus excavatum presented the sternal depression (21 ± 7) mm, CT depression index 2.9 ± 1.8, cardiac rotation angle (55.9 ± 9.8) degree, and PV angle (49.8 ± 14.0) degree, respectively. The sternal depression (17 mm) in cases with CT depression index less than 2.4 was smaller than those with CT depression index 2.4-2.9 (21 mm) and CT depression index larger than 2.9 (27 mm) (F 5.39, P<0.01). Cardiac rotation angle (49.7 degree) in cases with CT depression index less than 2.4 was smaller than those with CT depression index 2.4-2.9 (55.5 degree) and CT depression index larger than 2.9 (66.9 degree) (F=7.44, P<0.01). PV angle (58.7 degree) in cases with CT depression index less than 2.4 was larger than those with CT depression index 2.4-2.9 (46.5 degree) and CT depression index more than 2.9 (42.4 degree) ( F=3.33, P<0.05). Cardiac rotation angle of pectus excavatum had positive correlation with the CT depression index (γ=0.73, P<0.01). Conclusion: Spiral CT is a better tool for revealing chest deformity and corresponding cardiac rotation. The degree of sternal depression in pectus excavatum directly influences the cardiac rotation, and they had positive correlation. (authors)

  15. Sternal fracture: isolated lesion versus polytrauma from associated extrasternal injuries--analysis of 1,867 cases.

    Science.gov (United States)

    Odell, David D; Peleg, Kobi; Givon, Adi; Radomislensky, Irina; Makey, Ian; Decamp, Malcolm M; Whyte, Richard; Gangadharan, Sidhu P; Berger, Robert L

    2013-09-01

    Sternal fractures fall into two distinct categories as follows: (1) isolated sternal fracture (ISF) without associated injury and (2) polytrauma sternal fracture (PSF) with associated extrasternal injury. PSF can be sufficiently severe to require hospitalization, while ISF is usually a mild insult manageable in an ambulatory setting. Nonetheless, most patients with ISF are hospitalized. The disconnect between treatment based on existing evidence and actual clinical practice may be caused in large part by the small patient cohorts in published studies conducive to inaccurate conclusions. This article addresses the issue by analyzing prospectively collected data on a far larger population than hitherto available. The Israeli National Trauma Registry (INTR) collects data prospectively on patients admitted to trauma centers in Israel. We analyzed the INTR database on sternal fractures for demographics, mechanisms and severity of injury, diagnostic evaluation, treatment, and outcomes. Between 1997 and 2008, the INTR received data on 1,867 consecutive patients hospitalized with sternal fractures. The injury was sustained most often during motor vehicle accidents (84.1%), followed by falls (10.3%) and other blunt or penetrating mechanisms (5.6%). ISF was sustained in 26.4%, and PSF was sustained in 73.6%. Associated injuries involved most parts of the body. Cardiac contusions or lacerations were diagnosed in 1.8% of the 1,867 patients. ISF was associated with a lower incidence of cardiorespiratory compromise, more favorable trauma scores (Glasgow Coma Scale [GCS] score > 14, Revised Trauma Score > 11), and use of fewer intensive care facilities or operations compared with PSF. Endotracheal intubation, chest tube insertion, or thoracotomy was not performed in any ISF patient but was performed in 16.9% of the PSF cohort. The differences between ISF and PSF were statistically significant in all analyzed indices of injury severity. This study produced compelling evidence that

  16. Sternal Aspiration of Bone Marrow in Dogs: A Practical Approach for Canine Leishmaniasis Diagnosis and Monitoring

    Directory of Open Access Journals (Sweden)

    Rosa Paparcone

    2013-01-01

    Full Text Available Bone-marrow aspirate material is commonly considered as one of the most sensitive tissues for a reliable diagnosis of leishmaniasis. The procedure herein described may permit less experienced veterinarians to be familiar with a quick and safe assessment method for leishmaniasis diagnosis in their patients. Animals are positioned in right lateral recumbency, and the area corresponding to the second, third, or fourth sternebra is identified and aseptically prepared. A 18-gauge needle connected to a 10 mL syringe is driven through the skin, up to the bone wall, and firmly pushed forward while rotating. Entry into the sternebra’s cavity is clearly perceived by the fall of resistance offered by the cortex. Some 2,500 sternal bone-marrow samplings were safely and efficiently performed on 887 dogs of different breeds and aging from 6 months to 14 years, during eight years of clinical activity for routine diagnosis of canine leishmaniasis in pets or for the efficacy evaluation of anti-Leishmania immunobiologicals in dogs naturally exposed to parasite transmission. Most of the samples (1716 were from 387 dogs enrolled for anti-Leishmania vaccine studies. The safety of the method was particularly assessed on these dogs that as per study protocol were submitted to repeated bone-marrow aspirations (2–4 per year in follow-up examinations.

  17. The Fog signaling pathway: Insights into signaling in morphogenesis

    Science.gov (United States)

    Manning, Alyssa J.; Rogers, Stephen L.

    2014-01-01

    Epithelia form the building blocks of many tissue and organ types. Epithelial cells often form a contiguous 2-dimensional sheet that is held together by strong adhesions. The mechanical properties conferred by these adhesions allow the cells to undergo dramatic three-dimensional morphogenetic movements while maintaining cell–cell contacts during embryogenesis and post-embryonic development. The Drosophila Folded gastrulation pathway triggers epithelial cell shape changes that drive gastrulation and tissue folding and is one of the most extensively studied examples of epithelial morphogenesis. This pathway has yielded key insights into the signaling mechanisms and cellular machinery involved in epithelial remodeling. In this review, we discuss principles of morphogenesis and signaling that have been discovered through genetic and cell biological examination of this pathway. We also consider various regulatory mechanisms and the system's relevance to mammalian development. We propose future directions that will continue to broaden our knowledge of morphogenesis across taxa. PMID:25127992

  18. Morphogenesis and pattern formation in biological systems experiments and models

    CERN Document Server

    Noji, Sumihare; Ueno, Naoto; Maini, Philip

    2003-01-01

    A central goal of current biology is to decode the mechanisms that underlie the processes of morphogenesis and pattern formation. Concerned with the analysis of those phenomena, this book covers a broad range of research fields, including developmental biology, molecular biology, plant morphogenesis, ecology, epidemiology, medicine, paleontology, evolutionary biology, mathematical biology, and computational biology. In Morphogenesis and Pattern Formation in Biological Systems: Experiments and Models, experimental and theoretical aspects of biology are integrated for the construction and investigation of models of complex processes. This collection of articles on the latest advances by leading researchers not only brings together work from a wide spectrum of disciplines, but also provides a stepping-stone to the creation of new areas of discovery.

  19. The APC tumor suppressor is required for epithelial cell polarization and three-dimensional morphogenesis

    Science.gov (United States)

    Lesko, Alyssa C.; Goss, Kathleen H.; Yang, Frank F.; Schwertner, Adam; Hulur, Imge; Onel, Kenan; Prosperi, Jenifer R.

    2015-01-01

    The Adenomatous Polyposis Coli (APC) tumor suppressor has been previously implicated in the control of apical-basal polarity; yet, the consequence of APC loss-of-function in epithelial polarization and morphogenesis has not been characterized. To test the hypothesis that APC is required for the establishment of normal epithelial polarity and morphogenesis programs, we generated APC-knockdown epithelial cell lines. APC depletion resulted in loss of polarity and multi-layering on permeable supports, and enlarged, filled spheroids with disrupted polarity in 3D culture. Importantly, these effects of APC knockdown were independent of Wnt/β-catenin signaling, but were rescued with either full-length or a carboxy (c)-terminal segment of APC. Moreover, we identified a gene expression signature associated with APC knockdown that points to several candidates known to regulate cell-cell and cell-matrix communication. Analysis of epithelial tissues from mice and humans carrying heterozygous APC mutations further support the importance of APC as a regulator of epithelial behavior and tissue architecture. These data also suggest that the initiation of epithelial-derived tumors as a result of APC mutation or gene silencing may be driven by loss of polarity and dysmorphogenesis. PMID:25578398

  20. A global sensitivity analysis approach for morphogenesis models

    KAUST Repository

    Boas, Sonja E. M.

    2015-11-21

    Background Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand the relation between the uncertainty in the input and the output of such ‘black-box’ models, giving rise to the need for sensitivity analysis tools. In this paper, we introduce a workflow for a global sensitivity analysis approach to study the impact of single parameters and the interactions between them on the output of morphogenesis models. Results To demonstrate the workflow, we used a published, well-studied model of vascular morphogenesis. The parameters of this cellular Potts model (CPM) represent cell properties and behaviors that drive the mechanisms of angiogenic sprouting. The global sensitivity analysis correctly identified the dominant parameters in the model, consistent with previous studies. Additionally, the analysis provided information on the relative impact of single parameters and of interactions between them. This is very relevant because interactions of parameters impede the experimental verification of the predicted effect of single parameters. The parameter interactions, although of low impact, provided also new insights in the mechanisms of in silico sprouting. Finally, the analysis indicated that the model could be reduced by one parameter. Conclusions We propose global sensitivity analysis as an alternative approach to study the mechanisms of morphogenesis. Comparison of the ranking of the impact of the model parameters to knowledge derived from experimental data and from manipulation experiments can help to falsify models and to find the operand mechanisms in morphogenesis. The workflow is applicable to all ‘black-box’ models, including high-throughput in vitro models in which output measures are affected by a set of experimental perturbations.

  1. A global sensitivity analysis approach for morphogenesis models.

    Science.gov (United States)

    Boas, Sonja E M; Navarro Jimenez, Maria I; Merks, Roeland M H; Blom, Joke G

    2015-11-21

    Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand the relation between the uncertainty in the input and the output of such 'black-box' models, giving rise to the need for sensitivity analysis tools. In this paper, we introduce a workflow for a global sensitivity analysis approach to study the impact of single parameters and the interactions between them on the output of morphogenesis models. To demonstrate the workflow, we used a published, well-studied model of vascular morphogenesis. The parameters of this cellular Potts model (CPM) represent cell properties and behaviors that drive the mechanisms of angiogenic sprouting. The global sensitivity analysis correctly identified the dominant parameters in the model, consistent with previous studies. Additionally, the analysis provided information on the relative impact of single parameters and of interactions between them. This is very relevant because interactions of parameters impede the experimental verification of the predicted effect of single parameters. The parameter interactions, although of low impact, provided also new insights in the mechanisms of in silico sprouting. Finally, the analysis indicated that the model could be reduced by one parameter. We propose global sensitivity analysis as an alternative approach to study the mechanisms of morphogenesis. Comparison of the ranking of the impact of the model parameters to knowledge derived from experimental data and from manipulation experiments can help to falsify models and to find the operand mechanisms in morphogenesis. The workflow is applicable to all 'black-box' models, including high-throughput in vitro models in which output measures are affected by a set of experimental perturbations.

  2. Mechanical influences on morphogenesis of the knee joint revealed through morphological, molecular and computational analysis of immobilised embryos.

    Directory of Open Access Journals (Sweden)

    Karen A Roddy

    2011-02-01

    Full Text Available Very little is known about the regulation of morphogenesis in synovial joints. Mechanical forces generated from muscle contractions are required for normal development of several aspects of normal skeletogenesis. Here we show that biophysical stimuli generated by muscle contractions impact multiple events during chick knee joint morphogenesis influencing differential growth of the skeletal rudiment epiphyses and patterning of the emerging tissues in the joint interzone. Immobilisation of chick embryos was achieved through treatment with the neuromuscular blocking agent Decamethonium Bromide. The effects on development of the knee joint were examined using a combination of computational modelling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations, cell proliferation assays and in situ hybridisation to examine the expression of a selected panel of genes known to regulate joint development. This work revealed the precise changes to shape, particularly in the distal femur, that occur in an altered mechanical environment, corresponding to predicted changes in the spatial and dynamic patterns of mechanical stimuli and region specific changes in cell proliferation rates. In addition, we show altered patterning of the emerging tissues of the joint interzone with the loss of clearly defined and organised cell territories revealed by loss of characteristic interzone gene expression and abnormal expression of cartilage markers. This work shows that local dynamic patterns of biophysical stimuli generated from muscle contractions in the embryo act as a source of positional information guiding patterning and morphogenesis of the developing knee joint.

  3. Mechanical Influences on Morphogenesis of the Knee Joint Revealed through Morphological, Molecular and Computational Analysis of Immobilised Embryos

    Science.gov (United States)

    Roddy, Karen A.; Prendergast, Patrick J.; Murphy, Paula

    2011-01-01

    Very little is known about the regulation of morphogenesis in synovial joints. Mechanical forces generated from muscle contractions are required for normal development of several aspects of normal skeletogenesis. Here we show that biophysical stimuli generated by muscle contractions impact multiple events during chick knee joint morphogenesis influencing differential growth of the skeletal rudiment epiphyses and patterning of the emerging tissues in the joint interzone. Immobilisation of chick embryos was achieved through treatment with the neuromuscular blocking agent Decamethonium Bromide. The effects on development of the knee joint were examined using a combination of computational modelling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations, cell proliferation assays and in situ hybridisation to examine the expression of a selected panel of genes known to regulate joint development. This work revealed the precise changes to shape, particularly in the distal femur, that occur in an altered mechanical environment, corresponding to predicted changes in the spatial and dynamic patterns of mechanical stimuli and region specific changes in cell proliferation rates. In addition, we show altered patterning of the emerging tissues of the joint interzone with the loss of clearly defined and organised cell territories revealed by loss of characteristic interzone gene expression and abnormal expression of cartilage markers. This work shows that local dynamic patterns of biophysical stimuli generated from muscle contractions in the embryo act as a source of positional information guiding patterning and morphogenesis of the developing knee joint. PMID:21386908

  4. Rac1 modulates mammalian lung branching morphogenesis in part through canonical Wnt signaling.

    Science.gov (United States)

    Danopoulos, Soula; Krainock, Michael; Toubat, Omar; Thornton, Matthew; Grubbs, Brendan; Al Alam, Denise

    2016-12-01

    Lung branching morphogenesis relies on a number of factors, including proper epithelial cell proliferation and differentiation, cell polarity, and migration. Rac1, a small Rho GTPase, orchestrates a number of these cellular processes, including cell proliferation and differentiation, cellular alignment, and polarization. Furthermore, Rac1 modulates both noncanonical and canonical Wnt signaling, important pathways in lung branching morphogenesis. Culture of embryonic mouse lung explants in the presence of the Rac1 inhibitor (NSC23766) resulted in a dose-dependent decrease in branching. Increased cell death and BrdU uptake were notably seen in the mesenchyme, while no direct effect on the epithelium was observed. Moreover, vasculogenesis was impaired following Rac1 inhibition as shown by decreased Vegfa expression and impaired LacZ staining in Flk1-Lacz reporter mice. Rac1 inhibition decreased Fgf10 expression in conjunction with many of its associated factors. Moreover, using the reporter lines TOPGAL and Axin2-LacZ, there was an evident decrease in canonical Wnt signaling in the explants treated with the Rac1 inhibitor. Activation of canonical Wnt pathway using WNT3a or WNT7b only partially rescued the branching inhibition. Moreover, these results were validated on human explants, where Rac1 inhibition resulted in impaired branching and decreased AXIN2 and FGFR2b expression. We therefore conclude that Rac1 regulates lung branching morphogenesis, in part through canonical Wnt signaling. However, the exact mechanisms by which Rac1 interacts with canonical Wnt in human and mouse lung requires further investigation. Copyright © 2016 the American Physiological Society.

  5. Cell-based multi-parametric model of cleft progression during submandibular salivary gland branching morphogenesis.

    Directory of Open Access Journals (Sweden)

    Shayoni Ray

    Full Text Available Cleft formation during submandibular salivary gland branching morphogenesis is the critical step initiating the growth and development of the complex adult organ. Previous experimental studies indicated requirements for several epithelial cellular processes, such as proliferation, migration, cell-cell adhesion, cell-extracellular matrix (matrix adhesion, and cellular contraction in cleft formation; however, the relative contribution of each of these processes is not fully understood since it is not possible to experimentally manipulate each factor independently. We present here a comprehensive analysis of several cellular parameters regulating cleft progression during branching morphogenesis in the epithelial tissue of an early embryonic salivary gland at a local scale using an on lattice Monte-Carlo simulation model, the Glazier-Graner-Hogeweg model. We utilized measurements from time-lapse images of mouse submandibular gland organ explants to construct a temporally and spatially relevant cell-based 2D model. Our model simulates the effect of cellular proliferation, actomyosin contractility, cell-cell and cell-matrix adhesions on cleft progression, and it was used to test specific hypotheses regarding the function of these parameters in branching morphogenesis. We use innovative features capturing several aspects of cleft morphology and quantitatively analyze clefts formed during functional modification of the cellular parameters. Our simulations predict that a low epithelial mitosis rate and moderate level of actomyosin contractility in the cleft cells promote cleft progression. Raising or lowering levels of contractility and mitosis rate resulted in non-progressive clefts. We also show that lowered cell-cell adhesion in the cleft region and increased cleft cell-matrix adhesions are required for cleft progression. Using a classifier-based analysis, the relative importance of these four contributing cellular factors for effective cleft

  6. Scoring system to guide decision making for the use of gentamicin-impregnated collagen sponge to prevent deep sternal wound infection.

    Science.gov (United States)

    Benedetto, Umberto; Raja, Shahzad G

    2014-11-01

    The effectiveness of the routine retrosternal placement of a gentamicin-impregnated collagen sponge (GICS) implant before sternotomy closure is currently a matter of some controversy. We aimed to develop a scoring system to guide decision making for the use of GICS to prevent deep sternal wound infection. Fast backward elimination on predictors, including GICS, was performed using the Lawless and Singhal method. The scoring system was reported as a partial nomogram that can be used to manually obtain predicted individual risk of deep sternal wound infection from the regression model. Bootstrapping validation of the regression models was performed. The final populations consisted of 8750 adult patients undergoing cardiac surgery through full sternotomy during the study period. A total of 329 patients (3.8%) received GICS implant. The overall incidence of deep sternal wound infection was lower among patients who received GICS implant (0.6%) than patients who did not (2.01%) (P=.02). A nomogram to predict the individual risk for deep sternal wound infection was developed that included the use of GICS. Bootstrapping validation confirmed a good discriminative power of the models. The scoring system provides an impartial assessment of the decision-making process for clinicians to establish if GICS implant is effective in reducing the risk for deep sternal wound infection in individual patients undergoing cardiac surgery through full sternotomy. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  7. Newt tail regeneration: a model for gravity-dependent morphogenesis and clues to the molecular mechanisms involved.

    Science.gov (United States)

    Radugina, Elena A.; Almeida, Eduardo; Grigoryan, Eleonora

    factors and are expressed during development, we hypothesized they may play a role newt tail regenerative morphogenesis under altered g-levels. Specifically there is increasing evidence for HSPs expression changes as a result of hyper-and microgravity. HSPs are also expressed throughout regeneration, rather than just after surgery. To test this hypothesis we performed heat shock on intact and regenerating newts and collected tail tissues. In these experiments we observed that some tails had uplifted tips while others mimicked hook-like regenerates at 1g or 2g. These findings suggest that heat shock, and HSPs induction, may be involved in the mechanism responsible for gravity effects on morphogenesis, or at least interact with them. Current work underway is focused on analyzing the expression of mRNA and localization of proteins for two members of the group, Hsp70 and Hsp90. In summary, we developed and characterized a new practical animal model in which gravity mechanostimulation at 1g, versus unloading in aquaria, causes prominent effects on newt tail regenerative morphogenesis. This model can be achieved without the use of a centrifuge, significantly simplifying its research applications. Initial results using this model suggest that induction of HSPs may be involved in gravity regulation of newt tail regenerative morphogenesis. Further research based on this simple model may help to unravel mechanisms of gravity influence relevant not only to newt tail regeneration, but also to a broad range of other biological processes in amphibian models.

  8. Another cause of chest pain: Staphylococcus aureus sternal osteomyelitis in an otherwise healthy adult

    Directory of Open Access Journals (Sweden)

    Vacek TP

    2014-09-01

    Full Text Available Thomas P Vacek, Shahnaz Rehman, Shipeng Yu, Ankush Moza, Ragheb Assaly Department of Internal Medicine, The University of Toledo Medical Center, Toledo OH, USAAbstract: Chest pain requires a detailed differential diagnosis with good history-taking skills to differentiate between cardiogenic and noncardiogenic causes. Moreover, when other symptoms such as fever and elevated white blood cell count are involved, it may be necessary to consider causes that include infectious sources. A 53-year-old female with no significant past medical history returned to the hospital with recurrent complaints of chest pain that was constant, substernal, reproducible, and exacerbated with inspiration and expiration. The chest pain was thought to be noncardiogenic, as electrocardiography did not demonstrate changes, and cardiac enzymes were found to be negative for signs of ischemia. The patient's blood cultures were analyzed from a previous admission and were shown to be positive for Staphylococcus aureus. The patient was started empirically on vancomycin, which was later switched to ceftriaxone as the bacteria were more sensitive to this antibiotic. A transthoracic echocardiogram did not demonstrate any vegetation or signs of endocarditis. There was a small right pleural effusion discovered on X-ray. Therefore, computed tomography as well as magnetic resonance imaging of the chest were performed, and showed osteomyelitis of the chest. The patient was continued on intravenous ceftriaxone for a total of 6 weeks. Tests for HIV, hepatitis A, B, and C were all found to be negative. The patient had no history of childhood illness, recurrent infections, or previous trauma to the chest, and had had no recent respiratory infections, pneumonia, or any underlying lung condition. Hence, her condition was thought to be a case of primary sternal osteomyelitis without known cause.Keywords: substernal, pleuritic, myocardial infarction, differential

  9. Isomyosin expression patterns during rat heart morphogenesis: an immunohistochemical study

    NARCIS (Netherlands)

    de Groot, I. J.; Lamers, W. H.; Moorman, A. F.

    1989-01-01

    An immunohistochemical study of cardiac alpha and beta myosin heavy chain (MHC) expression during rat heart morphogenesis was performed. In tubular hearts (embryonic days, ED10-11) coexpression of both cardiac alpha and beta MHC was found throughout the heart, except for the left free wall of the

  10. Collective cell migration in morphogenesis, regeneration and cancer.

    NARCIS (Netherlands)

    Friedl, P.H.A.; Gilmour, D.

    2009-01-01

    The collective migration of cells as a cohesive group is a hallmark of the tissue remodelling events that underlie embryonic morphogenesis, wound repair and cancer invasion. In such migration, cells move as sheets, strands, clusters or ducts rather than individually, and use similar actin- and

  11. TDZ pulsing evaluation on the in vitro morphogenesis of peach palm.

    Science.gov (United States)

    Graner, Erika Mendes; Oberschelp, Gustavo Pedro Javier; Brondani, Gilvano Ebling; Batagin-Piotto, Katherine Derlene; de Almeida, Cristina Vieira; de Almeida, Marcílio

    2013-04-01

    Peach palm (Bactris gasipaes Kunth.) cropping is an excellent alternative to native species exploitation; nevertheless, the problems with seed germination and conventional propagation justify the use of in vitro culturing. Aiming to asses TDZ pulsing effect on B. gasipaes morphogenesis, explants obtained from unarmed microplants were maintained in two treatments, half of them in MS free medium (without growth regulator) and the other half in MS with TDZ (0.36 μM). Both groups were transferred to growth regulator-free MS medium following 14 days of culture. After 84 days of culture, TDZ pulsing increased the growth and development of the shoots, restricted the growth and development of the roots, with no influence on adventitious bud induction or somatic embryogenesis. Furthermore, development of prickles, thickening of roots and chlorotic leaves were noted under TDZ pulsing. Leaf sheath histological analysis showed an epidermal origin and no vascularization of these prickles.

  12. The HeartShield device reduces the risk for right ventricular damage in patients with deep sternal wound infection.

    Science.gov (United States)

    Ingemansson, Richard; Malmsjö, Malin; Lindstedt, Sandra

    2014-01-01

    Right ventricular rupture, resulting in serious bleeding, is a life-threatening complication associated with negative-pressure wound therapy (NPWT) in cardiac surgery. The use of a rigid barrier between the heart and the sharp sternal edges has been successfully tested on pigs. In the present article, we demonstrate increased safety in NPWT through the use of the HeartShield device. Six patients were treated with a specially designed device in combination with NPWT. The device consists of a horizontally placed disk covered in foam. The back of the T-shaped device sticks up between the sternal edges and up above skin level. This part of the device is also covered in foam. Drainage is performed through two holes at the top of the device. The device and foam are changed every second to third day, and -120 mm Hg of continuous therapy is used. Six patients were treated with traditional NPWT, serving as control group. No signs of calluslike formation were seen on the right ventricle in the group treated with the HeartShield device. In the conventional NPWT control group, all six patients had calluslike formation (>1 × 2 cm2) on the anterior part of the right ventricle. All patients in the HeartShield group had grade 1 epicardial petechial bleeding (the right ventricle. In the control group, one patient had grade 1 (2.0 cm2) epicardial petechial bleeding on the right ventricle. No major bleeding or mortality was observed in either group during the course of the study. The use of the HeartShield device significantly minimizes the contact between the right ventricle and the sternal edges, thereby decreasing the risk for life-threatening complications due to bleeding.

  13. A computational framework for 3D mechanical modeling of plant morphogenesis with cellular resolution.

    Directory of Open Access Journals (Sweden)

    Frédéric Boudon

    2015-01-01

    Full Text Available The link between genetic regulation and the definition of form and size during morphogenesis remains largely an open question in both plant and animal biology. This is partially due to the complexity of the process, involving extensive molecular networks, multiple feedbacks between different scales of organization and physical forces operating at multiple levels. Here we present a conceptual and modeling framework aimed at generating an integrated understanding of morphogenesis in plants. This framework is based on the biophysical properties of plant cells, which are under high internal turgor pressure, and are prevented from bursting because of the presence of a rigid cell wall. To control cell growth, the underlying molecular networks must interfere locally with the elastic and/or plastic extensibility of this cell wall. We present a model in the form of a three dimensional (3D virtual tissue, where growth depends on the local modulation of wall mechanical properties and turgor pressure. The model shows how forces generated by turgor-pressure can act both cell autonomously and non-cell autonomously to drive growth in different directions. We use simulations to explore lateral organ formation at the shoot apical meristem. Although different scenarios lead to similar shape changes, they are not equivalent and lead to different, testable predictions regarding the mechanical and geometrical properties of the growing lateral organs. Using flower development as an example, we further show how a limited number of gene activities can explain the complex shape changes that accompany organ outgrowth.

  14. On the genetic control of planar growth during tissue morphogenesis in plants.

    Science.gov (United States)

    Enugutti, Balaji; Kirchhelle, Charlotte; Schneitz, Kay

    2013-06-01

    Tissue morphogenesis requires extensive intercellular communication. Plant organs are composites of distinct radial cell layers. A typical layer, such as the epidermis, is propagated by stereotypic anticlinal cell divisions. It is presently unclear what mechanisms coordinate cell divisions relative to the plane of a layer, resulting in planar growth and maintenance of the layer structure. Failure in the regulation of coordinated growth across a tissue may result in spatially restricted abnormal growth and the formation of a tumor-like protrusion. Therefore, one way to approach planar growth control is to look for genetic mutants that exhibit localized tumor-like outgrowths. Interestingly, plants appear to have evolved quite robust genetic mechanisms that govern these aspects of tissue morphogenesis. Here we provide a short summary of the current knowledge about the genetics of tumor formation in plants and relate it to the known control of coordinated cell behavior within a tissue layer. We further portray the integuments of Arabidopsis thaliana as an excellent model system to study the regulation of planar growth. The value of examining this process in integuments was established by the recent identification of the Arabidopsis AGC VIII kinase UNICORN as a novel growth suppressor involved in the regulation of planar growth and the inhibition of localized ectopic growth in integuments and other floral organs. An emerging insight is that misregulation of central determinants of adaxial-abaxial tissue polarity can lead to the formation of spatially restricted multicellular outgrowths in several tissues. Thus, there may exist a link between the mechanisms regulating adaxial-abaxial tissue polarity and planar growth in plants.

  15. Use of a sternal elevator to reverse complete airway obstruction secondary to anterior mediastinal mass in an anesthetized child

    Directory of Open Access Journals (Sweden)

    Maria E. Linnaus

    2016-05-01

    Full Text Available Patients with an anterior mediastinal mass pose significant risk for cardiorespiratory compromise during surgical procedures and general anesthesia. Several techniques have been described to reverse airway obstruction in these patients. In extreme circumstances, patients may require cardiac bypass or extracorporeal membrane oxygenation (ECMO until definitive treatment of the mass and patient stabilization is achieved. We present a case in which the RulTract® system was used for emergency sternal elevation as a bridge to ECMO in acute respiratory collapse in an 11-year-old female with a minimally symptomatic anterior mediastinal mass.

  16. CRIM1 complexes with ß-catenin and cadherins, stabilizes cell-cell junctions and is critical for neural morphogenesis.

    Directory of Open Access Journals (Sweden)

    Virgilio G Ponferrada

    Full Text Available In multicellular organisms, morphogenesis is a highly coordinated process that requires dynamically regulated adhesion between cells. An excellent example of cellular morphogenesis is the formation of the neural tube from the flattened epithelium of the neural plate. Cysteine-rich motor neuron protein 1 (CRIM1 is a single-pass (type 1 transmembrane protein that is expressed in neural structures beginning at the neural plate stage. In the frog Xenopus laevis, loss of function studies using CRIM1 antisense morpholino oligonucleotides resulted in a failure of neural development. The CRIM1 knockdown phenotype was, in some cases, mild and resulted in perturbed neural fold morphogenesis. In severely affected embryos there was a dramatic failure of cell adhesion in the neural plate and complete absence of neural structures subsequently. Investigation of the mechanism of CRIM1 function revealed that it can form complexes with ß-catenin and cadherins, albeit indirectly, via the cytosolic domain. Consistent with this, CRIM1 knockdown resulted in diminished levels of cadherins and ß-catenin in junctional complexes in the neural plate. We conclude that CRIM1 is critical for cell-cell adhesion during neural development because it is required for the function of cadherin-dependent junctions.

  17. Sternal Cleft and Pectus Excavatum: A Combined Approach for the Correction of a Complex Anterior Chest Wall Malformation in a Teenager.

    Science.gov (United States)

    Tocchioni, Francesca; Ghionzoli, Marco; Lo Piccolo, Roberto; Deaconu, Diana E; Facchini, Flavio; Milanez De Campos, Jose R; Messineo, Antonio

    2015-06-01

    Congenital sternal cleft is a rare chest wall malformation. Because of the flexibility of the chest in infants, surgical repair should be performed by primary closure in the neonatal period. In adolescents and adults, different techniques have been suggested to overcome the lack of sternal bone tissue. We describe a very rare case of an 18-year-old woman with a complete bifid sternum associated with pectus excavatum for whom a satisfactory cosmetic and functional result was obtained by adequate surgical planning, which entailed a combination of two standardized surgical techniques. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  18. Intersection of FOXO- and RUNX1-mediated gene expression programs in single breast epithelial cells during morphogenesis and tumor progression.

    Science.gov (United States)

    Wang, Lixin; Brugge, Joan S; Janes, Kevin A

    2011-10-04

    Gene expression networks are complicated by the assortment of regulatory factors that bind DNA and modulate transcription combinatorially. Single-cell measurements can reveal biological mechanisms hidden by population averages, but their value has not been fully explored in the context of mRNA regulation. Here, we adapted a single-cell expression profiling technique to examine the gene expression program downstream of Forkhead box O (FOXO) transcription factors during 3D breast epithelial acinar morphogenesis. By analyzing patterns of mRNA fluctuations among individual matrix-attached epithelial cells, we found that a subset of FOXO target genes was jointly regulated by the transcription factor Runt-related transcription factor 1 (RUNX1). Knockdown of RUNX1 causes hyperproliferation and abnormal morphogenesis, both of which require normal FOXO function. Down-regulating RUNX1 and FOXOs simultaneously causes widespread oxidative stress, which arrests proliferation and restores normal acinar morphology. In hormone-negative breast cancers lacking human epidermal growth factor receptor 2 (HER2) amplification, we find that RUNX1 down-regulation is strongly associated with up-regulation of FOXO1, which may be required to support growth of RUNX1-negative tumors. The coordinate function of these two tumor suppressors may provide a failsafe mechanism that inhibits cancer progression.

  19. Rapid and Minimally Traumatic Replacement of Stimulator Extension Cables: Technical Note on a Novel Use for Sternal Wire.

    Science.gov (United States)

    Henderson, Fraser; Takacs, Istvan

    2017-01-01

    Troubleshooting of deep brain stimulators (DBSs, Activa SC/PC/RC Medtronic PLC, Minneapolis, Minnesota, USA) sometimes results in a decision to replace a tunneled stretch-coil extension cable. We present a simple technique to accomplish this atraumatically without a tunneling tool. In the treatment of patients with a DBS, complication avoidance and efficiency of operative time are paramount. We sought to find the safest, most effective, and fastest method of performing the conceptually simple yet technically nuanced act of replacing lead extension cables. We connected #6 (8.0 metric) surgical steel 18″ (45-cm) monofilament (Ethicon US, LLC, Somerville, New Jersey, USA), also known as #6 sternal wire, in line with DBS extension cables (Medtronic DBS Extension 37086-60) in novel fashion to overcome intraprocedural hurdles encountered during the past decade in a busy functional neurosurgery service. Patients tolerate the procedure well and return home shortly after recovery with no complications. A less expensive and faster technique for passing pulse generator extension cables may be the use of a sternal wire. Using the described technique, pulse generators may be quickly and safely adjusted from side to side and site to site as the clinical situation dictates. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. EphB/syndecan-2 signaling in dendritic spine morphogenesis

    DEFF Research Database (Denmark)

    Ethell, I M; Irie, F; Kalo, M S

    2001-01-01

    We previously reported that the cell surface proteoglycan syndecan-2 can induce dendritic spine formation in hippocampal neurons. We demonstrate here that the EphB2 receptor tyrosine kinase phosphorylates syndecan-2 and that this phosphorylation event is crucial for syndecan-2 clustering and spine...... formation. Syndecan-2 is tyrosine phosphorylated and forms a complex with EphB2 in mouse brain. Dominant-negative inhibition of endogenous EphB receptor activities blocks clustering of endogenous syndecan-2 and normal spine formation in cultured hippocampal neurons. This is the first evidence that Eph...... receptors play a physiological role in dendritic spine morphogenesis. Our observations suggest that spine morphogenesis is triggered by the activation of Eph receptors, which causes tyrosine phosphorylation of target molecules, such as syndecan-2, in presumptive spines....

  1. Extending Graphic Statics for User-Controlled Structural Morphogenesis

    OpenAIRE

    Fivet, Corentin; Zastavni, Denis; Cap, Jean-François; Structural Morphology Group International Seminar 2011

    2011-01-01

    The first geometrical definitions of any structure are of primary importance when considering pertinence and efficiency in structural design processes. Engineering history has taught us how graphic statics can be a very powerful tool since it allows the designer to take shapes and forces into account simultaneously. However, current and past graphic statics methods are more suitable for analysis than structural morphogenesis. This contribution introduces new graphical methods that can supp...

  2. Effect of oxygen on morphogenesis and polypeptide expression by Mucor racemosus

    International Nuclear Information System (INIS)

    Phillips, G.J.; Borgia, P.T.

    1985-01-01

    The morphology of Mucor racemosus in cultures continuously sparged with nitrogen gas was investigated. When appropriate precautions were taken to prevent oxygen from entering the cultures, the morphology of the cells was uniformly yeastlike irrespective of the N 2 flow rate. When small amounts of oxygen entered the cultures the resulting microaerobic conditions evoked mycelial development. Polypeptides synthesized by aerobic mycelia, microaerobic mycelia, anaerobic yeasts, and yeasts grown in a CO 2 atmosphere were compared by two-dimensional gel electrophoresis. The results indicated that a large number of differences in polypeptide expression exist when microaerobic mycelia or anaerobic yeasts are compared with aerobic mycelia and that these alterations correlate with a change from an oxidative to a fermentative metabolic mode. The authors hypothesize that oxygen regulates the expression of polypeptides involved in both the metabolic mode and in morphogenesis

  3. Notochord vacuoles are lysosome-related organelles that function in axis and spine morphogenesis.

    Science.gov (United States)

    Ellis, Kathryn; Bagwell, Jennifer; Bagnat, Michel

    2013-03-04

    The notochord plays critical structural and signaling roles during vertebrate development. At the center of the vertebrate notochord is a large fluid-filled organelle, the notochord vacuole. Although these highly conserved intracellular structures have been described for decades, little is known about the molecular mechanisms involved in their biogenesis and maintenance. Here we show that zebrafish notochord vacuoles are specialized lysosome-related organelles whose formation and maintenance requires late endosomal trafficking regulated by the vacuole-specific Rab32a and H(+)-ATPase-dependent acidification. We establish that notochord vacuoles are required for body axis elongation during embryonic development and identify a novel role in spine morphogenesis. Thus, the vertebrate notochord plays important structural roles beyond early development.

  4. Embryo mechanics: balancing force production with elastic resistance during morphogenesis.

    Science.gov (United States)

    Davidson, Lance A

    2011-01-01

    Morphogenesis requires the spatial and temporal control of embryo mechanics, including force production and mechanical resistance to those forces, to coordinate tissue deformation and large-scale movements. Thus, biomechanical processes play a key role in directly shaping the embryo. Additional roles for embryo mechanics during development may include the patterning of positional information and to provide feedback to ensure the success of morphogenetic movements in shaping the larval body and organs. To understand the multiple roles of mechanics during development requires familiarity with engineering principles of the mechanics of structures, the viscoelastic properties of biomaterials, and the integration of force and stress within embryonic structures as morphogenesis progresses. In this chapter, we review the basic engineering principles of biomechanics as they relate to morphogenesis, introduce methods for quantifying embryo mechanics and the limitations of these methods, and outline a formalism for investigating the role of embryo mechanics in birth defects. We encourage the nascent field of embryo mechanics to adopt standard engineering terms and test methods so that studies of diverse organisms can be compared and universal biomechanical principles can be revealed. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Morphogenesis in bat wings: linking development, evolution and ecology.

    Science.gov (United States)

    Adams, Rick A

    2008-01-01

    The evolution of powered flight in mammals required specific developmental shifts from an ancestral limb morphology to one adapted for flight. Through studies of comparative morphogenesis, investigators have quantified points and rates of divergence providing important insights into how wings evolved in mammals. Herein I compare growth,development and skeletogenesis of forelimbs between bats and the more ancestral state provided by the rat (Rattus norvegicus)and quantify growth trajectories that illustrate morphological divergence both developmentally and evolutionarily. In addition, I discuss how wing shape is controlled during morphogenesis by applying multivariate analyses of wing bones and wing membranes and discuss how flight dynamics are stabilized during flight ontogeny. Further, I discuss the development of flight in bats in relation to the ontogenetic niche and how juveniles effect populational foraging patterns. In addition, I provide a hypothetical ontogenetic landscape model that predicts how and when selection is most intense during juvenile morphogenesis and test this model with data from a population of the little brown bat, Myotis lucifugus. (c) 2007 S. Karger AG, Basel

  6. Factors associated with methicillin-resistant coagulase-negative staphylococci as causing organisms in deep sternal wound infections after cardiac surgery

    Directory of Open Access Journals (Sweden)

    R. Sommerstein

    2015-07-01

    Full Text Available Established preoperative antibiotic prophylaxis in cardiac surgery is ineffective against methicillin-resistant coagulase-negative staphylococci (CoNS. This case–control study aimed to determine factors predicting deep sternal wound infections due to methicillin-resistant CoNS. All cardiac surgery patients undergoing sternotomy between June 2009 and March 2013 prospectively documented in a Swiss tertiary care center were included. Among 1999 patients, 82 (4.1% developed deep sternal wound infection. CoNS were causal in 36 (44% patients, with 25/36 (69% being methicillin resistant. Early reintervention for noninfectious causes (odds ratio (OR 4.3; 95% confidence interval (CI 1.9–9.5 was associated with methicillin-resistant CoNS deep sternal wound infection. Among CoNS deep sternal wound infection, perioperative antimicrobial therapy (p 0.002, early reintervention for noninfectious causes (OR 7.9; 95% CI 0.9–71.1 and time between surgery and diagnosis of infection over 21 days (OR 10.8; 95% CI 1.2–97.8 were associated with methicillin resistance. These findings may help to better tailor preoperative antimicrobial prophylaxis.

  7. Major bleeding during negative pressure wound/V.A.C.®--therapy for postsurgical deep sternal wound infection--a critical appraisal

    NARCIS (Netherlands)

    van Wingerden, Jan J.; Segers, Patrique; Jekel, Lilian

    2011-01-01

    Negative-pressure wound therapy, commercially known as vacuum-assisted closure (V.A.C.®) therapy, has become one of the most popular (and efficacious) interim (prior to flap reconstruction) or definite methods of managing deep sternal wound infection. Complications such as profuse bleeding, which

  8. Daptomycin as a possible new treatment option for surgical management of Methicillin-Resistant Staphylococcus aureus sternal wound infection after cardiac surgery

    Directory of Open Access Journals (Sweden)

    Emmert Alexander

    2010-08-01

    Full Text Available Abstract We present a case of a 77-year old female who had undergone a coronary artery bypass grafting with an aortic valve replacement and developed three month later a Methicillin-Resistant Staphylococcus aureus (MRSA sternal wound infection which was successful treated with Daptomycin combined with vacuum-assisted closure (VAC.

  9. New potential markers of in vitro tomato morphogenesis identified by mRNA differential display.

    Science.gov (United States)

    Torelli, A; Soragni, E; Bolchi, A; Petrucco, S; Ottonello, S; Branca, C

    1996-12-01

    The identification of plant genes involved in early phases of in vitro morphogenesis can not only contribute to our understanding of the processes underlying growth regulator-controlled determination, but also provide novel markers for evaluating the outcome of in vitro regeneration experiments. To search for such genes and to monitor changes in gene expression accompanying in vitro regeneration, we have adapted the mRNA differential display technique to the comparative analysis of a model system of tomato cotyledons that can be driven selectively toward either shoot or callus formation by means of previously determined growth regulator supplementations. Hormone-independent transcriptional modulation (mainly down-regulation) has been found to be the most common event, indicating that a non-specific reprogramming of gene expression quantitatively predominates during the early phases of in vitro culture. However, cDNA fragments representative of genes that are either down-regulated or induced in a programme-specific manner could also be identified, and two of them (G35, G36) were further characterized. One of these cDNA fragments, G35, corresponds to an mRNA that is down-regulated much earlier in callus- (day 2) than in shoot-determined explants (day 6). The other, G36, identifies an mRNA that is transiently expressed in shoot-determined explants only, well before any macroscopic signs of differentiation become apparent, and thus exhibits typical features of a morphogenetic marker.

  10. Clavicles, interclavicles, gastralia, and sternal ribs in sauropod dinosaurs: new reports from diplodocidae and their morphological, functional and evolutionary implications.

    Science.gov (United States)

    Tschopp, Emanuel; Mateus, Octávio

    2013-03-01

    Ossified gastralia, clavicles and sternal ribs are known in a variety of reptilians, including dinosaurs. In sauropods, however, the identity of these bones is controversial. The peculiar shapes of these bones complicate their identification, which led to various differing interpretations in the past. Here we describe different elements from the chest region of diplodocids, found near Shell, Wyoming, USA. Five morphotypes are easily distinguishable: (A) elongated, relatively stout, curved elements with a spatulate and a bifurcate end resemble much the previously reported sauropod clavicles, but might actually represent interclavicles; (B) short, L-shaped elements, mostly preserved as a symmetrical pair, probably are the real clavicles, as indicated by new findings in diplodocids; (C) slender, rod-like bones with rugose ends are highly similar to elements identified as sauropod sternal ribs; (D) curved bones with wide, probably medial ends constitute the fourth morphotype, herein interpreted as gastralia; and (E) irregularly shaped elements, often with extended rugosities, are included into the fifth morphotype, tentatively identified as sternal ribs and/or intercostal elements. To our knowledge, the bones previously interpreted as sauropod clavicles were always found as single bones, which sheds doubt on the validity of their identification. Various lines of evidence presented herein suggest they might actually be interclavicles - which are single elements. This would be the first definitive evidence of interclavicles in dinosauromorphs. Previously supposed interclavicles in the early sauropodomorph Massospondylus or the theropods Oviraptor and Velociraptor were later reinterpreted as clavicles or furculae. Independent from their identification, the existence of the reported bones has both phylogenetic and functional significance. Their presence in non-neosauropod Eusauropoda and Flagellicaudata and probable absence in rebbachisaurs and Titanosauriformes shows a

  11. A Julia set model of field-directed morphogenesis: developmental biology and artificial life.

    Science.gov (United States)

    Levin, M

    1994-04-01

    One paradigm used in understanding the control of morphogenetic events is the concept of positional information, where sub-organismic components (such as cells) act in response to positional cues. It is important to determine what kinds of spatiotemporal patterns may be obtained by such a method, and what the characteristics of such a morphogenetic process might be. This paper presents a computer model of morphogenesis based on gene activity driven by interpreting a positional information field. In this model, the interactions of mutually regulating developmental genes are viewed as a map from R2 to R2, and are modeled by the complex number algebra. Functions in complex variables are used to simulate genetic interactions resulting in position-dependent differentiation. This is shown to be equivalent to computing modified Julia sets, and is seen to be sufficient to produce a very rich set of morphologies which are similar in appearance and several important characteristics to those of real organisms. The properties of this model can be used to study the potential role of fields and positional information as guiding factors in morphogenesis, as the model facilitates the study of static images, time-series (movies) and experimental alterations of the developmental process. It is thus shown that gene interactions can be modeled as a multi-dimensional algebra, and that only two interacting genes are sufficient for (i) complex pattern formation, (ii) chaotic differentiation behavior, and (iii) production of sharp edges from a continuous positional information field. This model is meant to elucidate the properties of the process of positional information-guided biomorphogenesis, not to serve as a simulation of any particular organism's development. Good quantitative data are not currently available on the interplay of gene products in morphogenesis. Thus, no attempt is made to link the images produced with actual pictures of any particular real organism. A brief

  12. Ret and Etv4 Promote Directed Movements of Progenitor Cells during Renal Branching Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Paul Riccio

    2016-02-01

    Full Text Available Branching morphogenesis of the epithelial ureteric bud forms the renal collecting duct system and is critical for normal nephron number, while low nephron number is implicated in hypertension and renal disease. Ureteric bud growth and branching requires GDNF signaling from the surrounding mesenchyme to cells at the ureteric bud tips, via the Ret receptor tyrosine kinase and coreceptor Gfrα1; Ret signaling up-regulates transcription factors Etv4 and Etv5, which are also critical for branching. Despite extensive knowledge of the genetic control of these events, it is not understood, at the cellular level, how renal branching morphogenesis is achieved or how Ret signaling influences epithelial cell behaviors to promote this process. Analysis of chimeric embryos previously suggested a role for Ret signaling in promoting cell rearrangements in the nephric duct, but this method was unsuited to study individual cell behaviors during ureteric bud branching. Here, we use Mosaic Analysis with Double Markers (MADM, combined with organ culture and time-lapse imaging, to trace the movements and divisions of individual ureteric bud tip cells. We first examine wild-type clones and then Ret or Etv4 mutant/wild-type clones in which the mutant and wild-type sister cells are differentially and heritably marked by green and red fluorescent proteins. We find that, in normal kidneys, most individual tip cells behave as self-renewing progenitors, some of whose progeny remain at the tips while others populate the growing UB trunks. In Ret or Etv4 MADM clones, the wild-type cells generated at a UB tip are much more likely to remain at, or move to, the new tips during branching and elongation, while their Ret-/- or Etv4-/- sister cells tend to lag behind and contribute only to the trunks. By tracking successive mitoses in a cell lineage, we find that Ret signaling has little effect on proliferation, in contrast to its effects on cell movement. Our results show that Ret

  13. [Vacuum-assisted Closure (VAC) Treatment for Sternal Infection in a Patient after Cardiovascular Surgery; Report of a Case].

    Science.gov (United States)

    Shima, Shotaro; Okamura, Kennichi; Morizumi, Sei; Kanamori, Taro; Ichihara, Tetsuya; Kawata, Mitsuhiro; Suematsu, Yoshihiro

    2015-03-01

    One year ago, a 42-year-old woman underwent aortic root replacement because of a pseudoaneurysm that developed at the site of an anastomosis after ascending aortic replacement for acute aortic dissection. Six months later, she complained of fever and cough. A computed tomography revealed recurrence of the peudoaneurysm at the proximal anastomosis of the aortic root replacement. After emergency re-do aortic root replacement, she was admitted to intensive care unit (ICU) without sternal closure because of mediastinitis. The mediastinitis was managed by debridement and lavage drainage, followed by vacuum-assisted closure (VAC) treatment. The VAC treatment facilitated wound healing and active rehabilitation using a portable device. Finally, the wound was closed completely using a skin graft. VAC treatment is considered very useful in a case of post-sternotomy madiastinitis.

  14. Tenascin-C in peripheral nerve morphogenesis.

    Science.gov (United States)

    Chiquet, M; Wehrle-Haller, B

    1994-01-01

    The extracellular matrix (ECM) molecule tenascin/cytotactin (TN-C) is expressed at a high level by satellite (glial precursor) cells in developing peripheral nerves of the chick embryo; synthesis of its mRNA peaks at the time period when axonal growth is maximal. When offered as a substrate in vitro, TN-C mediates neurite outgrowth by both motor and sensory neurons. The ability to grow neurites on TN-C is developmentally regulated: sensory neurons from 4-day chick embryos (the stage at which peripheral nerves start to develop) grow immediately and rapidly, whereas neurons from older embryos respond with a long delay. A TN-C domain responsible for this activity is located within the C-terminal (distal) portion of TN-C subunits. Integrin receptors seem to be involved on peripheral neurites because their growth on TN-C is completely blocked by antibodies to beta 1 integrins. In striking contrast to neuronal processes, nerve satellite cells can attach to a TN-C substrate but are completely inhibited in their migratory activity. Artificial substrate borders between tenascin and fibronectin or laminin act as selective barriers that allow neurites to pass while holding up satellite cells. The repulsive action of TN-C on satellite cells is similar to that observed for other cell types and is likely to be mediated by additional TN-C domains. In view of these data, it is surprising that mice seem to develop normally without a functional TN-C gene. TN-C is likely to be redundant, that is, its dual action on cell adhesion is shared by other molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Ras1 interacts with multiple new signaling and cytoskeletal loci in Drosophila eggshell patterning and morphogenesis.

    Science.gov (United States)

    Schnorr, J D; Holdcraft, R; Chevalier, B; Berg, C A

    2001-10-01

    Little is known about the genes that interact with Ras signaling pathways to regulate morphogenesis. The synthesis of dorsal eggshell structures in Drosophila melanogaster requires multiple rounds of Ras signaling followed by dramatic epithelial sheet movements. We took advantage of this process to identify genes that link patterning and morphogenesis; we screened lethal mutations on the second chromosome for those that could enhance a weak Ras1 eggshell phenotype. Of 1618 lethal P-element mutations tested, 13 showed significant enhancement, resulting in forked and fused dorsal appendages. Our genetic and molecular analyses together with information from the Berkeley Drosophila Genome Project reveal that 11 of these lines carry mutations in previously characterized genes. Three mutations disrupt the known Ras1 cell signaling components Star, Egfr, and Blistered, while one mutation disrupts Sec61beta, implicated in ligand secretion. Seven lines represent cell signaling and cytoskeletal components that are new to the Ras1 pathway; these are Chickadee (Profilin), Tec29, Dreadlocks, POSH, Peanut, Smt3, and MESK2, a suppressor of dominant-negative Ksr. A twelfth insertion disrupts two genes, Nrk, a "neurospecific" receptor tyrosine kinase, and Tpp, which encodes a neuropeptidase. These results suggest that Ras1 signaling during oogenesis involves novel components that may be intimately associated with additional signaling processes and with the reorganization of the cytoskeleton. To determine whether these Ras1 Enhancers function upstream or downstream of the Egf receptor, four mutations were tested for their ability to suppress an activated Egfr construct (lambdatop) expressed in oogenesis exclusively in the follicle cells. Mutations in Star and l(2)43Bb had no significant effect upon the lambdatop eggshell defect whereas smt3 and dock alleles significantly suppressed the lambdatop phenotype.

  16. Giga-voxel computational morphogenesis for structural design

    DEFF Research Database (Denmark)

    Aage, Niels; Andreassen, Erik; Lazarov, Boyan Stefanov

    2017-01-01

    In the design of industrial products ranging from hearing aidsto automobiles and aeroplanes, material is distributed so as to maximize the performance and minimize the cost. Historically, human intuition and insight have driven the evolution of mechanical design, recently assisted by computer...... aeroplane wing designs, which translates into are duction in fuel consumption of about 40–200 tonnes per year per aeroplane. Our morphogenesis process is generally applicable, not only to mechanical design, but also to flow systems3, antennas4,nano-optics5 and micro-systems6,7...

  17. Morphogenesis and Complexity of the Tumor Patterns

    Science.gov (United States)

    Izquierdo-Kulich, E.; Nieto-Villar, J. M.

    A mechanism to describe the apoptosis process at mesoscopic level through p53 is proposed in this paper. A deterministic model given by three differential equations is deduced from the mesoscopic approach, which exhibits sustained oscillations caused by a supercritical Andronov-Hopf bifurcation. Taking as hypothesis that the p53 sustained oscillation is the fundamental mechanism for apoptosis regulation; the model predicts that it is necessary a strict control of p53 to stimulated it, which is an important consideration to established new therapy strategy to fight cancer. The mathematical modeling of tumor growth allows us to describe the most important regularities of these systems. A stochastic model, based on the most important processes that take place at the level of individual cells, is proposed to predict the dynamical behavior of the expected radius of the tumor and its fractal dimension. It was found that the tumor has a characteristic fractal dimension, which contains the necessary information to predict the tumor growth until it reaches a stationary state. The mathematical modeling of tumor growth is an approach to explain the complex nature of these systems. A model that describes tumor growth was obtained by using a mesoscopic formalism and fractal dimension. This model theoretically predicts the relation between the morphology of the cell pattern and the mitosis/apoptosis quotient that helps to predict tumor growth from tumoral cells fractal dimension. The relation between the tumor macroscopic morphology and the cell pattern morphology is also determined. This could explain why the interface fractal dimension decreases with the increase of the cell pattern fractal dimension and consequently with the increase of the mitosis/apoptosis relation. Indexes to characterize tumoral cell proliferation and invasion capacities are proposed and used to predict the growth of different types of tumors. These indexes also show that the proliferation capacity is

  18. Structure-function analysis of STRUBBELIG, an Arabidopsis atypical receptor-like kinase involved in tissue morphogenesis.

    Directory of Open Access Journals (Sweden)

    Prasad Vaddepalli

    Full Text Available Tissue morphogenesis in plants requires the coordination of cellular behavior across clonally distinct histogenic layers. The underlying signaling mechanisms are presently being unraveled and are known to include the cell surface leucine-rich repeat receptor-like kinase STRUBBELIG in Arabidopsis. To understand better its mode of action an extensive structure-function analysis of STRUBBELIG was performed. The phenotypes of 20 EMS and T-DNA-induced strubbelig alleles were assessed and homology modeling was applied to rationalize their possible effects on STRUBBELIG protein structure. The analysis was complemented by phenotypic, cell biological, and pharmacological investigations of a strubbelig null allele carrying genomic rescue constructs encoding fusions between various mutated STRUBBELIG proteins and GFP. The results indicate that STRUBBELIG accepts quite some sequence variation, reveal the biological importance for the STRUBBELIG N-capping domain, and reinforce the notion that kinase activity is not essential for its function in vivo. Furthermore, individual protein domains of STRUBBELIG cannot be related to specific STRUBBELIG-dependent biological processes suggesting that process specificity is mediated by factors acting together with or downstream of STRUBBELIG. In addition, the evidence indicates that biogenesis of a functional STRUBBELIG receptor is subject to endoplasmic reticulum-mediated quality control, and that an MG132-sensitive process regulates its stability. Finally, STRUBBELIG and the receptor-like kinase gene ERECTA interact synergistically in the control of internode length. The data provide genetic and molecular insight into how STRUBBELIG regulates intercellular communication in tissue morphogenesis.

  19. Morphogenesis of Strongyloides stercoralis infective larvae requires the DAF-16 ortholog FKTF-1.

    Directory of Open Access Journals (Sweden)

    Michelle L Castelletto

    2009-04-01

    Full Text Available Based on metabolic and morphological similarities between infective third-stage larvae of parasitic nematodes and dauer larvae of Caenorhabditis elegans, it is hypothesized that similar genetic mechanisms control the development of these forms. In the parasite Strongyloides stercoralis, FKTF-1 is an ortholog of DAF-16, a forkhead transcription factor that regulates dauer larval development in C. elegans. Using transgenesis, we investigated the role of FKTF-1 in S. stercoralis' infective larval development. In first-stage larvae, GFP-tagged recombinant FKTF-1b localizes to the pharynx and hypodermis, tissues remodeled in infective larvae. Activating and inactivating mutations at predicted AKT phosphorylation sites on FKTF-1b give constitutive cytoplasmic and nuclear localization of the protein, respectively, indicating that its post-translational regulation is similar to other FOXO-class transcription factors. Mutant constructs designed to interfere with endogenous FKTF-1b function altered the intestinal and pharyngeal development of the larvae and resulted in some transgenic larvae failing to arrest in the infective stage. Our findings indicate that FKTF-1b is required for proper morphogenesis of S. stercoralis infective larvae and support the overall hypothesis of similar regulation of dauer development in C. elegans and the formation of infective larvae in parasitic nematodes.

  20. Physics and the canalization of morphogenesis: a grand challenge in organismal biology

    International Nuclear Information System (INIS)

    Von Dassow, Michelangelo; Davidson, Lance A

    2011-01-01

    Morphogenesis takes place against a background of organism-to-organism and environmental variation. Therefore, fundamental questions in the study of morphogenesis include: How are the mechanical processes of tissue movement and deformation affected by that variability, and in turn, how do the mechanic of the system modulate phenotypic variation? We highlight a few key factors, including environmental temperature, embryo size and environmental chemistry that might perturb the mechanics of morphogenesis in natural populations. Then we discuss several ways in which mechanics—including feedback from mechanical cues—might influence intra-specific variation in morphogenesis. To understand morphogenesis it will be necessary to consider whole-organism, environment and evolutionary scales because these larger scales present the challenges that developmental mechanisms have evolved to cope with. Studying the variation organisms express and the variation organisms experience will aid in deciphering the causes of birth defects

  1. Loss of laminin alpha 1 results in multiple structural defects and divergent effects on adhesion during vertebrate optic cup morphogenesis

    Science.gov (United States)

    Bryan, Chase D.; Chien, Chi-Bin; Kwan, Kristen M.

    2016-01-01

    The vertebrate eye forms via a complex set of morphogenetic events. The optic vesicle evaginates and undergoes transformative shape changes to form the optic cup, in which neural retina and retinal pigmented epithelium enwrap the lens. It has long been known that a complex, glycoprotein-rich extracellular matrix layer surrounds the developing optic cup throughout the process, yet the functions of the matrix and its specific molecular components have remained unclear. Previous work established a role for laminin extracellular matrix in particular steps of eye development, including optic vesicle evagination, lens differentiation, and retinal ganglion cell polarization, yet it is unknown what role laminin might play in the early process of optic cup formation subsequent to the initial step of optic vesicle evagination. Here, we use the zebrafish lama1 mutant (lama1UW1) to determine the function of laminin during optic cup morphogenesis. Using live imaging, we find, surprisingly, that loss of laminin leads to divergent effects on focal adhesion assembly in a spatiotemporally-specific manner, and that laminin is required for multiple steps of optic cup morphogenesis, including optic stalk constriction, invagination, and formation of a spherical lens. Laminin is not required for single cell behaviors and changes in cell shape. Rather, in lama1UW1 mutants, loss of epithelial polarity and altered adhesion lead to defective tissue architecture and formation of a disorganized retina. These results demonstrate that the laminin extracellular matrix plays multiple critical roles regulating adhesion and polarity to establish and maintain tissue structure during optic cup morphogenesis. PMID:27339294

  2. Autocrine EGF receptor activation mediates endothelial cell migration and vascular morphogenesis induced by VEGF under interstitial flow

    International Nuclear Information System (INIS)

    Semino, Carlos E.; Kamm, Roger D.; Lauffenburger, Douglas A.

    2006-01-01

    We show here that autocrine ligand activation of epidermal growth factor (EGF) receptor in combination with interstitial flow is critically involved in the morphogenetic response of endothelial cells to VEGF stimulation. Human umbilical vein endothelial cell (HUVEC) monolayers cultured on a collagen gel and exposed to low interstitial flow in the absence of EGF and VEGF remained viable and mitotic but exhibited little evidence of vascular morphogenesis. Addition of VEGF produced a flow-dependent morphogenetic response within 48 to 72 h, characterized by branched capillary-like structures. The response was substantially abolished by inhibitors related to the autocrine EGF receptor pathway including Galardin, AG1478, PD98059, and an EGF receptor-blocking antibody, indicating that regulation of the morphogenetic process operates via autocrine EGF receptor activation. Moreover, we observed that in our system the EGF receptor was always activated independently of the interstitial flow, and, in addition, the EGF receptor inhibitors used above reduced the phosphorylation state of the receptor, correlating with inhibition of capillary morphogenesis. Finally, 5'bromo-2'-deoxyuridine (BrdU) labeling identified dividing cells at the monolayer but not in the extending capillary-like structures. EGF pathway inhibitors Galardin and AG1478 did not reduce BrdU incorporation in the monolayer, indicating that the EGF-receptor-mediated morphogenetic behavior is mainly due to cell migration rather than proliferation. Based on these results, we propose a two-step model for in vitro capillary morphogenesis in response to VEGF stimulation with interstitial fluid flow: monolayer maintenance by mitotic activity independent of EGF receptors and a migratory response mediated by autocrine EGF receptor activation wherein cells establish capillary-like structures

  3. Conjoined twins: morphogenesis of the heart and a review.

    Science.gov (United States)

    Gilbert-Barness, Enid; Debich-Spicer, Diane; Opitz, John M

    2003-08-01

    Five cases of conjoined twins have been studied. These included three thoracopagus twins, one monocephalus diprosopus (prosop = face), and one dicephalus dipus dibrachus. The thoracopagus twins were conjoined only from the upper thorax to the umbilicus with a normal foregut. These three cases shared a single complex multiventricular heart, one with a four chambered heart with one atrium and one ventricle belonging to each twin with complex venous and arterial connection; two had a seven chambered heart with four atria and three ventricles. The mono-cephalus diprosopus twins had a single heart with tetralogy of Fallot. The dicephalus twins had two separate axial skeletons to the sacrum, two separate hearts were connected between the right atria with a shared inferior vena cava. Thoracopagus twinning is associated with complex cardiac malformations. The cardiac anlagen in cephalopagus or diprosopus are diverted and divided along with the entire rostral end of the embryonic disc and result in two relatively normal shared hearts. However, in thoracopagus twins the single heart is multiventricular and suggests very early union with fusion of the cardiac anlagen before significant differentiation. Cardiac morphogenesis in conjoined twins therefore appears to depend on the site of the conjoined fusion and the temporal and spatial influence that determines morphogenesis as well as abnormally oriented embryonic axes. Copyright 2003 Wiley-Liss, Inc.

  4. Tissue Motion and Assembly During Early Cardiovascular Morphogenesis

    Science.gov (United States)

    Rongish, Brenda

    2010-03-01

    Conventional dogma in the field of cardiovascular developmental biology suggests that cardiac precursor cells migrate to the embryonic midline to form a tubular heart. These progenitors are believed to move relative to their extracellular matrix (ECM); responding to stimulatory and inhibitory cues in their environment. The tubular heart that is formed by 30 hours post fertilization is comprised of two concentric layers: the muscular myocardium and the endothelial-like endocardium, which are separated by a thick layer of ECM believed to be secreted predominantly by the myocardial cells. Here we describe the origin and motility of fluorescently tagged endocardial precursors in transgenic (Tie1-YFP) quail embryos (R. Lansford, Caltech) using epifluorescence time-lapse imaging. To visualize the environment of migrating endocardial progenitors, we labeled two ECM components, fibronectin and fibrillin-2, via in vivo microinjection of fluorochrome-conjugated monoclonal antibodies. Dynamic imaging was performed at stages encompassing tubular heart assembly and early looping. We established the motion of endocardial precursor cells and presumptive cardiac ECM fibrils using both object tracking and particle image velocimetry (image cross correlation). We determined the relative importance of directed cell autonomous motility versus passive tissue movements in endocardial morphogenesis. The data show presumptive endocardial cells and cardiac ECM fibrils are swept passively into the anterior and posterior poles of the elongating tubular heart. These quantitative data indicate the contribution of cell autonomous motility displayed by endocardial precursors is limited. Thus, tissue motion drives most of the cell displacements during endocardial morphogenesis.

  5. Notochord morphogenesis in mice: Current understanding & open questions.

    Science.gov (United States)

    Balmer, Sophie; Nowotschin, Sonja; Hadjantonakis, Anna-Katerina

    2016-05-01

    The notochord is a structure common to all chordates, and the feature that the phylum Chordata has been named after. It is a rod-like mesodermal structure that runs the anterior-posterior length of the embryo, adjacent to the ventral neural tube. The notochord plays a critical role in embryonic tissue patterning, for example the dorsal-ventral patterning of the neural tube. The cells that will come to form the notochord are specified at gastrulation. Axial mesodermal cells arising at the anterior primitive streak migrate anteriorly as the precursors of the notochord and populate the notochordal plate. Yet, even though a lot of interest has centered on investigating the functional and structural roles of the notochord, we still have a very rudimentary understanding of notochord morphogenesis. The events driving the formation of the notochord are rapid, taking place over the period of approximately a day in mice. In this commentary, we provide an overview of our current understanding of mouse notochord morphogenesis, from the initial specification of axial mesendodermal cells at the primitive streak, the emergence of these cells at the midline on the surface of the embryo, to their submergence and organization of the stereotypically positioned notochord. We will also discuss some key open questions. Developmental Dynamics 245:547-557, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. The unfolded protein response is required for dendrite morphogenesis

    Science.gov (United States)

    Wei, Xing; Howell, Audrey S; Dong, Xintong; Taylor, Caitlin A; Cooper, Roshni C; Zhang, Jianqi; Zou, Wei; Sherwood, David R; Shen, Kang

    2015-01-01

    Precise patterning of dendritic fields is essential for the formation and function of neuronal circuits. During development, dendrites acquire their morphology by exuberant branching. How neurons cope with the increased load of protein production required for this rapid growth is poorly understood. Here we show that the physiological unfolded protein response (UPR) is induced in the highly branched Caenorhabditis elegans sensory neuron PVD during dendrite morphogenesis. Perturbation of the IRE1 arm of the UPR pathway causes loss of dendritic branches, a phenotype that can be rescued by overexpression of the ER chaperone HSP-4 (a homolog of mammalian BiP/ grp78). Surprisingly, a single transmembrane leucine-rich repeat protein, DMA-1, plays a major role in the induction of the UPR and the dendritic phenotype in the UPR mutants. These findings reveal a significant role for the physiological UPR in the maintenance of ER homeostasis during morphogenesis of large dendritic arbors. DOI: http://dx.doi.org/10.7554/eLife.06963.001 PMID:26052671

  7. Major bleeding during negative pressure wound/V.A.C.® - therapy for postsurgical deep sternal wound infection - a critical appraisal

    Directory of Open Access Journals (Sweden)

    Segers Patrique

    2011-09-01

    Full Text Available Abstract Negative-pressure wound therapy, commercially known as vacuum-assisted closure (V.A.C.® therapy, has become one of the most popular (and efficacious interim (prior to flap reconstruction or definite methods of managing deep sternal wound infection. Complications such as profuse bleeding, which may occur during negative-pressure therapy but not necessarily due to it, are often attributed to a single factor and reported as such. However, despite the wealth of clinical experience internationally available, information regarding certain simple considerations is still lacking. Garnering information on all the factors that could possibly influence the outcome has become more difficult due to a (fortunate decrease in the incidence of deep sternal wound infection. If more insight is to be gained from fewer clinical cases, then various potentially confounding factors should be fully disclosed before complications can be attributed to the technique itself or improvements to negative-pressure wound therapy for deep sternal wound infection can be accepted as evidence-based and the guidelines for its use adapted. The authors propose the adoption of a simple checklist in such cases.

  8. Morphogenesis checkpoint kinase Swe1 is the executor of lipolysis-dependent cell-cycle progression.

    Science.gov (United States)

    Chauhan, Neha; Visram, Myriam; Cristobal-Sarramian, Alvaro; Sarkleti, Florian; Kohlwein, Sepp D

    2015-03-10

    Cell growth and division requires the precise duplication of cellular DNA content but also of membranes and organelles. Knowledge about the cell-cycle-dependent regulation of membrane and storage lipid homeostasis is only rudimentary. Previous work from our laboratory has shown that the breakdown of triacylglycerols (TGs) is regulated in a cell-cycle-dependent manner, by activation of the Tgl4 lipase by the major cyclin-dependent kinase Cdc28. The lipases Tgl3 and Tgl4 are required for efficient cell-cycle progression during the G1/S (Gap1/replication phase) transition, at the onset of bud formation, and their absence leads to a cell-cycle delay. We now show that defective lipolysis activates the Swe1 morphogenesis checkpoint kinase that halts cell-cycle progression by phosphorylation of Cdc28 at tyrosine residue 19. Saturated long-chain fatty acids and phytosphingosine supplementation rescue the cell-cycle delay in the Tgl3/Tgl4 lipase-deficient strain, suggesting that Swe1 activity responds to imbalanced sphingolipid metabolism, in the absence of TG degradation. We propose a model by which TG-derived sphingolipids are required to activate the protein phosphatase 2A (PP2A(Cdc55)) to attenuate Swe1 phosphorylation and its inhibitory effect on Cdc28 at the G1/S transition of the cell cycle.

  9. HMP-1/α-catenin promotes junctional mechanical integrity during morphogenesis.

    Directory of Open Access Journals (Sweden)

    Thanh Thi Kim Vuong-Brender

    Full Text Available Adherens junctions (AJs are key structures regulating tissue integrity and maintaining adhesion between cells. During morphogenesis, junctional proteins cooperate closely with the actomyosin network to drive cell movement and shape changes. How the junctions integrate the mechanical forces in space and in time during an in vivo morphogenetic event is still largely unknown, due to a lack of quantitative data. To address this issue, we inserted a functional Fluorescence Resonance Energy Transfer (FRET-based force biosensor within HMP-1/α-catenin of Caenorhabditis elegans. We find that the tension exerted on HMP-1 has a cell-specific distribution, is actomyosin-dependent, but is regulated differently from the tension on the actin cortex during embryonic elongation. By using time-lapse analysis of mutants and tissue-specific rescue experiments, we confirm the role of VAB-9/Claudin as an actin bundle anchor. Nevertheless, the tension exerted on HMP-1 did not increase in the absence of VAB-9/Claudin, suggesting that HMP-1 activity is not upregulated to compensate for loss of VAB-9. Our data indicate that HMP-1 does not modulate HMR-1/E-cadherin turnover, is required to recruit junctional actin but not stress fiber-like actin bundles. Altogether, our data suggest that HMP-1/α-catenin acts to promote the mechanical integrity of adherens junctions.

  10. Wnts and wing: Wnt signaling in vertebrate limb development and musculoskeletal morphogenesis.

    Science.gov (United States)

    Yang, Yingzi

    2003-11-01

    In the past twenty years, secreted signaling molecules of the Wnt family have been found to play a central role in controlling embryonic development from hydra to human. In the developing vertebrate limb, Wnt signaling is required for limb bud initiation, early limb patterning (which is governed by several well-characterized signaling centers), and, finally, late limb morphogenesis events. Wnt ligands are unique, in that they can activate several different receptor-mediated signal transduction pathways. The most extensively studied Wnt pathway is the canonical Wnt pathway, which controls gene expression by stabilizing beta-catenin in regulating a diverse array of biological processes. Recently, more attention has been given to the noncanonical Wnt pathway, which is beta-catenin-independent. The noncanonical Wnt pathway signals through activating Ca(2+) flux, JNK activation, and both small and heterotrimeric G proteins, to induce changes in gene expression, cell adhesion, migration, and polarity. Abnormal Wnt signaling leads to developmental defects and human diseases affecting either tissue development or homeostasis. Further understanding of the biological function and signaling mechanism of Wnt signaling is essential for the development of novel preventive and therapeutic approaches of human diseases. This review provides a critical perspective on how Wnt signaling regulates different developmental processes. As Wnt signaling in tumor formation has been reviewed extensively elsewhere, this part is not included in the review of the clinical significance of Wnt signaling.

  11. The cell wall-localized atypical β-1,3 glucanase ZERZAUST controls tissue morphogenesis in Arabidopsis thaliana.

    Science.gov (United States)

    Vaddepalli, Prasad; Fulton, Lynette; Wieland, Jennifer; Wassmer, Katrin; Schaeffer, Milena; Ranf, Stefanie; Schneitz, Kay

    2017-06-15

    Orchestration of cellular behavior in plant organogenesis requires integration of intercellular communication and cell wall dynamics. The underlying signaling mechanisms are poorly understood. Tissue morphogenesis in Arabidopsis depends on the receptor-like kinase STRUBBELIG. Mutations in ZERZAUST were previously shown to result in a strubbelig -like mutant phenotype. Here, we report on the molecular identification and functional characterization of ZERZAUST We show that ZERZAUST encodes a putative GPI-anchored β-1,3 glucanase suggested to degrade the cell wall polymer callose. However, a combination of in vitro , cell biological and genetic experiments indicate that ZERZAUST is not involved in the regulation of callose accumulation. Nonetheless, Fourier-transformed infrared-spectroscopy revealed that zerzaust mutants show defects in cell wall composition. Furthermore, the results indicate that ZERZAUST represents a mobile apoplastic protein, and that its carbohydrate-binding module family 43 domain is required for proper subcellular localization and function whereas its GPI anchor is dispensable. Our collective data reveal that the atypical β-1,3 glucanase ZERZAUST acts in a non-cell-autonomous manner and is required for cell wall organization during tissue morphogenesis. © 2017. Published by The Company of Biologists Ltd.

  12. Epithelial Markers aSMA, Krt14, and Krt19 Unveil Elements of Murine Lacrimal Gland Morphogenesis and Maturation.

    Science.gov (United States)

    Kuony, Alison; Michon, Frederic

    2017-01-01

    As an element of the lacrimal apparatus, the lacrimal gland (LG) produces the aqueous part of the tear film, which protects the eye surface. Therefore, a defective LG can lead to serious eyesight impairment. Up to now, little is known about LG morphogenesis and subsequent maturation. In this study, we delineated elements of the cellular and molecular events involved in LG formation by using three epithelial markers, namely aSMA, Krt14, and Krt19. While aSMA marked a restricted epithelial population of the terminal end buds (TEBs) in the forming LG, Krt14 was found in the whole embryonic LG epithelial basal cell layer. Interestingly, Krt19 specifically labeled the presumptive ductal domain and subsequently, the luminal cell layer. By combining these markers, the Fucci reporter mouse strain and genetic fate mapping of the Krt14 + population, we demonstrated that LG epithelium expansion is fuelled by a patterned cell proliferation, and to a lesser extent by epithelial reorganization and possible mesenchymal-to-epithelial transition. We pointed out that this epithelial reorganization, which is associated with apoptosis, regulated the lumen formation. Finally, we showed that the inhibition of Notch signaling prevented the ductal identity from setting, and led to a LG covered by ectopic TEBs. Taken together our results bring a deeper understanding on LG morphogenesis, epithelial domain identity, and organ expansion.

  13. Drosophila sosie functions with βH-Spectrin and actin organizers in cell migration, epithelial morphogenesis and cortical stability

    Science.gov (United States)

    Urwyler, Olivier; Cortinas-Elizondo, Fabiola; Suter, Beat

    2012-01-01

    Summary Morphogenesis in multicellular organisms requires the careful coordination of cytoskeletal elements, dynamic regulation of cell adhesion and extensive cell migration. sosie (sie) is a novel gene required in various morphogenesis processes in Drosophila oogenesis. Lack of sie interferes with normal egg chamber packaging, maintenance of epithelial integrity and control of follicle cell migration, indicating that sie is involved in controlling epithelial integrity and cell migration. For these functions sie is required both in the germ line and in the soma. Consistent with this, Sosie localizes to plasma membranes in the germ line and in the somatic follicle cells and is predicted to present an EGF-like domain on the extracellular side. Two positively charged residues, C-terminal to the predicted transmembrane domain (on the cytoplasmic side), are required for normal plasma membrane localization of Sosie. Because sie also contributes to normal cortical localization of βH-Spectrin, it appears that cortical βH-Spectrin mediates some of the functions of sosie. sie also interacts with the genes coding for the actin organizers Filamin and Profilin and, in the absence of sie function, F-actin is less well organized and nurse cells frequently fuse. PMID:23213377

  14. Drosophila sosie functions with β(H)-Spectrin and actin organizers in cell migration, epithelial morphogenesis and cortical stability.

    Science.gov (United States)

    Urwyler, Olivier; Cortinas-Elizondo, Fabiola; Suter, Beat

    2012-10-15

    Morphogenesis in multicellular organisms requires the careful coordination of cytoskeletal elements, dynamic regulation of cell adhesion and extensive cell migration. sosie (sie) is a novel gene required in various morphogenesis processes in Drosophila oogenesis. Lack of sie interferes with normal egg chamber packaging, maintenance of epithelial integrity and control of follicle cell migration, indicating that sie is involved in controlling epithelial integrity and cell migration. For these functions sie is required both in the germ line and in the soma. Consistent with this, Sosie localizes to plasma membranes in the germ line and in the somatic follicle cells and is predicted to present an EGF-like domain on the extracellular side. Two positively charged residues, C-terminal to the predicted transmembrane domain (on the cytoplasmic side), are required for normal plasma membrane localization of Sosie. Because sie also contributes to normal cortical localization of β(H)-Spectrin, it appears that cortical β(H)-Spectrin mediates some of the functions of sosie. sie also interacts with the genes coding for the actin organizers Filamin and Profilin and, in the absence of sie function, F-actin is less well organized and nurse cells frequently fuse.

  15. The cell shape proteins MreB and MreC control cell morphogenesis by positioning cell wall synthetic complexes.

    Science.gov (United States)

    Divakaruni, Arun V; Baida, Cyril; White, Courtney L; Gober, James W

    2007-10-01

    MreB, the bacterial actin homologue, is thought to function in spatially co-ordinating cell morphogenesis in conjunction with MreC, a protein that wraps around the outside of the cell within the periplasmic space. In Caulobacter crescentus, MreC physically associates with penicillin-binding proteins (PBPs) which catalyse the insertion of intracellularly synthesized precursors into the peptidoglycan cell wall. Here we show that MreC is required for the spatial organization of components of the peptidoglycan-synthesizing holoenzyme in the periplasm and MreB directs the localization of a peptidoglycan precursor synthesis protein in the cytosol. Additionally, fluorescent vancomycin (Van-FL) labelling revealed that the bacterial cytoskeletal proteins MreB and FtsZ, as well as MreC and RodA, were required for peptidoglycan synthetic activity. MreB and FtsZ were found to be required for morphogenesis of the polar stalk. FtsZ was required for a cell cycle-regulated burst of peptidoglycan synthesis early in the cell cycle resulting in the synthesis of cross-band structures, whereas MreB was required for lengthening of the stalk. Thus, the bacterial cytoskeleton and cell shape-determining proteins such as MreC, function in concert to orchestrate the localization of cell wall synthetic complexes resulting in spatially co-ordinated and efficient peptidoglycan synthetic activity.

  16. Ott1 (Rbm15) is essential for placental vascular branching morphogenesis and embryonic development of the heart and spleen.

    Science.gov (United States)

    Raffel, Glen D; Chu, Gerald C; Jesneck, Jonathan L; Cullen, Dana E; Bronson, Roderick T; Bernard, Olivier A; Gilliland, D Gary

    2009-01-01

    The infant leukemia-associated gene Ott1 (Rbm15) has broad regulatory effects within murine hematopoiesis. However, germ line Ott1 deletion results in fetal demise prior to embryonic day 10.5, indicating additional developmental requirements for Ott1. The spen gene family, to which Ott1 belongs, has a transcriptional activation/repression domain and RNA recognition motifs and has a significant role in the development of the head and thorax in Drosophila melanogaster. Early Ott1-deficient embryos show growth retardation and incomplete closure of the notochord. Further analysis demonstrated placental defects in the spongiotrophoblast and syncytiotrophoblast layers, resulting in an arrest of vascular branching morphogenesis. The rescue of the placental defect using a conditional allele with a trophoblast-sparing cre transgene allowed embryos to form a normal placenta and survive gestation. This outcome showed that the process of vascular branching morphogenesis in Ott1-deficient animals was regulated by the trophoblast compartment rather than the fetal vasculature. Mice surviving to term manifested hyposplenia and abnormal cardiac development. Analysis of global gene expression of Ott1-deficient embryonic hearts showed an enrichment of hypoxia-related genes and a significant alteration of several candidate genes critical for cardiac development. Thus, Ott1-dependent pathways, in addition to being implicated in leukemogenesis, may also be important for the pathogenesis of placental insufficiency and cardiac malformations.

  17. Drosophila convoluted/dALS is an essential gene required for tracheal tube morphogenesis and apical matrix organization.

    Science.gov (United States)

    Swanson, Lianna E; Yu, Marcus; Nelson, Kevin S; Laprise, Patrick; Tepass, Ulrich; Beitel, Greg J

    2009-04-01

    Insulin-like growth factors (IGFs) control cell and organism growth through evolutionarily conserved signaling pathways. The mammalian acid-labile subunit (ALS) is a secreted protein that complexes with IGFs to modulate their activity. Recent work has shown that a Drosophila homolog of ALS, dALS, can also complex with and modulate the activity of a Drosophila IGF. Here we report the first mutations in the gene encoding dALS. Unexpectedly, we find that these mutations are allelic to a previously described mutation in convoluted (conv), a gene required for epithelial morphogenesis. In conv mutants, the tubes of the Drosophila tracheal system become abnormally elongated without altering tracheal cell number. conv null mutations cause larval lethality, but do not disrupt several processes required for tracheal tube size control, including septate junction formation, deposition of a lumenal/apical extracellular matrix, and lumenal secretion of Vermiform and Serpentine, two putative matrix-modifying proteins. Clearance of lumenal matrix and subcellular localization of clathrin also appear normal in conv mutants. However, we show that Conv/dALS is required for the dynamic organization of the transient lumenal matrix and normal structure of the cuticle that lines the tracheal lumen. These and other data suggest that the Conv/dALS-dependent tube size control mechanism is distinct from other known processes involved in tracheal tube size regulation. Moreover, we present evidence indicating that Conv/dALS has a novel, IGF-signaling independent function in tracheal morphogenesis.

  18. Developmental toxicity assessment of common excipients using a stem cell-based in vitro morphogenesis model.

    Science.gov (United States)

    Yuan, Chloe J; Marikawa, Yusuke

    2017-11-01

    Various chemical compounds can inflict developmental toxicity when sufficiently high concentrations are exposed to embryos at the critical stages of development. Excipients, such as coloring agents and preservatives, are pharmacologically inactive ingredients that are included in various medications, foods, and cosmetics. However, concentrations that may adversely affect embryo development are largely unknown for most excipients. Here, the lowest observed adverse effect level (LOAEL) to inflict developmental toxicity was assessed for three coloring agents (allura red, brilliant blue, and tartrazine) and three preservatives (butylated hydroxyanisole, metabisulfite, and methylparaben). Adverse impact of a compound exposure was determined using the stem cell-based in vitro morphogenesis model, in which three-dimensional cell aggregates, or embryoid bodies (EBs), recapitulate embryonic processes of body axis elongation and patterning. LOAEL to impair EB morphogenesis was 200 μM for methylparaben, 400 μM for butylated hydroxyanisole, 600 μM for allura red and brilliant blue, and 1000 μM for metabisulfite. Gene expression analyses of excipient-treated EBs revealed that butylated hydroxyanisole and methylparaben significantly altered profiles of developmental regulators involved in axial elongation and patterning of the body. The present study may provide a novel in vitro approach to investigate potential developmental toxicity of common excipients with mechanistic insights. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Ras GTPases Modulate Morphogenesis, Sporulation and Cellulase Gene Expression in the Cellulolytic Fungus Trichoderma reesei

    Science.gov (United States)

    Zhang, Jiwei; Zhang, Yanmei; Zhong, Yaohua; Qu, Yinbo; Wang, Tianhong

    2012-01-01

    Background The model cellulolytic fungus Trichoderma reesei (teleomorph Hypocrea jecorina) is capable of responding to environmental cues to compete for nutrients in its natural saprophytic habitat despite its genome encodes fewer degradative enzymes. Efficient signalling pathways in perception and interpretation of environmental signals are indispensable in this process. Ras GTPases represent a kind of critical signal proteins involved in signal transduction and regulation of gene expression. In T. reesei the genome contains two Ras subfamily small GTPases TrRas1 and TrRas2 homologous to Ras1 and Ras2 from S. cerevisiae, but their functions remain unknown. Methodology/Principal Findings Here, we have investigated the roles of GTPases TrRas1 and TrRas2 during fungal morphogenesis and cellulase gene expression. We show that both TrRas1 and TrRas2 play important roles in some cellular processes such as polarized apical growth, hyphal branch formation, sporulation and cAMP level adjustment, while TrRas1 is more dominant in these processes. Strikingly, we find that TrRas2 is involved in modulation of cellulase gene expression. Deletion of TrRas2 results in considerably decreased transcription of cellulolytic genes upon growth on cellulose. Although the strain carrying a constitutively activated TrRas2G16V allele exhibits increased cellulase gene transcription, the cbh1 and cbh2 expression in this mutant still strictly depends on cellulose, indicating TrRas2 does not directly mediate the transmission of the cellulose signal. In addition, our data suggest that the effect of TrRas2 on cellulase gene is exerted through regulation of transcript abundance of cellulase transcription factors such as Xyr1, but the influence is independent of cAMP signalling pathway. Conclusions/Significance Together, these findings elucidate the functions for Ras signalling of T. reesei in cellular morphogenesis, especially in cellulase gene expression, which contribute to deciphering the

  20. Cdc42 regulates epithelial cell polarity and cytoskeletal function during kidney tubule development

    DEFF Research Database (Denmark)

    Elias, Bertha C; Das, Amrita; Parekh, Diptiben V

    2015-01-01

    The Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, migration, differentiation and morphogenesis. Although previous studies have shown that Cdc42 is required for proper epithelial development and main......The Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, migration, differentiation and morphogenesis. Although previous studies have shown that Cdc42 is required for proper epithelial development...

  1. Mechanical basis of morphogenesis and convergent evolution of spiny seashells

    KAUST Repository

    Chirat, R.; Moulton, D. E.; Goriely, A.

    2013-01-01

    Convergent evolution is a phenomenon whereby similar traits evolved independently in not closely related species, and is often interpreted in functional terms. Spines in mollusk seashells are classically interpreted as having repeatedly evolved as a defense in response to shell-crushing predators. Here we consider the morphogenetic process that shapes these structures and underlies their repeated emergence. We develop a mathematical model for spine morphogenesis based on the mechanical interaction between the secreting mantle edge and the calcified shell edge to which the mantle adheres during shell growth. It is demonstrated that a large diversity of spine structures can be accounted for through small variations in control parameters of this natural mechanical process. This physical mechanism suggests that convergent evolution of spines can be understood through a generic morphogenetic process, and provides unique perspectives in understanding the phenotypic evolution of this second largest phylum in the animal kingdom.

  2. Some peculiarities of inflorescences morphogenesis in Brexia (Celastraceae

    Directory of Open Access Journals (Sweden)

    Ivan A. Savinov

    2013-04-01

    Full Text Available Comparative analysis of inflorescences structure for 6 species of the Brexia(according to the last revision by Schatz & Lowry II (2004 is conducted. For one species, B. madagascariensis, the shoots growth and development, inflorescence morphogenesis details are studied. It is determined inflorescences of Brexiaspecies (have described in literature as cymes, pseudo-umbellate, corymbiform, sessile in fascicles; and including for some species cauliflory presents a different variations of ancestral form transformation – dichasial system (closed thyrse. Apparently, presence of a big bracts may be consider as ancestral, plesiomorphic character for the genus; and derivate ones – reduction of bracts and presence of minute bracteoles in pedicel basis only. Inflorescences of Brexiain typically may be considered as bracteous. Process of reduction the number of clusters and separate flowers is accompanied by different variations of their transformations.

  3. Complex dynamics and morphogenesis an introduction to nonlinear science

    CERN Document Server

    Misbah, Chaouqi

    2017-01-01

    This book offers an introduction to the physics of nonlinear phenomena through two complementary approaches: bifurcation theory and catastrophe theory. Readers will be gradually introduced to the language and formalisms of nonlinear sciences, which constitute the framework to describe complex systems. The difficulty with complex systems is that their evolution cannot be fully predicted because of the interdependence and interactions between their different components. Starting with simple examples and working toward an increasing level of universalization, the work explores diverse scenarios of bifurcations and elementary catastrophes which characterize the qualitative behavior of nonlinear systems. The study of temporal evolution is undertaken using the equations that characterize stationary or oscillatory solutions, while spatial analysis introduces the fascinating problem of morphogenesis. Accessible to undergraduate university students in any discipline concerned with nonlinear phenomena (physics, mathema...

  4. The green seaweed Ulva: a model system to study morphogenesis.

    Science.gov (United States)

    Wichard, Thomas; Charrier, Bénédicte; Mineur, Frédéric; Bothwell, John H; Clerck, Olivier De; Coates, Juliet C

    2015-01-01

    Green macroalgae, mostly represented by the Ulvophyceae, the main multicellular branch of the Chlorophyceae, constitute important primary producers of marine and brackish coastal ecosystems. Ulva or sea lettuce species are some of the most abundant representatives, being ubiquitous in coastal benthic communities around the world. Nonetheless the genus also remains largely understudied. This review highlights Ulva as an exciting novel model organism for studies of algal growth, development and morphogenesis as well as mutualistic interactions. The key reasons that Ulva is potentially such a good model system are: (i) patterns of Ulva development can drive ecologically important events, such as the increasing number of green tides observed worldwide as a result of eutrophication of coastal waters, (ii) Ulva growth is symbiotic, with proper development requiring close association with bacterial epiphytes, (iii) Ulva is extremely developmentally plastic, which can shed light on the transition from simple to complex multicellularity and (iv) Ulva will provide additional information about the evolution of the green lineage.

  5. Mechanical basis of morphogenesis and convergent evolution of spiny seashells

    KAUST Repository

    Chirat, R.

    2013-03-25

    Convergent evolution is a phenomenon whereby similar traits evolved independently in not closely related species, and is often interpreted in functional terms. Spines in mollusk seashells are classically interpreted as having repeatedly evolved as a defense in response to shell-crushing predators. Here we consider the morphogenetic process that shapes these structures and underlies their repeated emergence. We develop a mathematical model for spine morphogenesis based on the mechanical interaction between the secreting mantle edge and the calcified shell edge to which the mantle adheres during shell growth. It is demonstrated that a large diversity of spine structures can be accounted for through small variations in control parameters of this natural mechanical process. This physical mechanism suggests that convergent evolution of spines can be understood through a generic morphogenetic process, and provides unique perspectives in understanding the phenotypic evolution of this second largest phylum in the animal kingdom.

  6. The MAPKERK-1,2 pathway integrates distinct and antagonistic signals from TGF alpha and FGF7 in morphogenesis of mouse mammary epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Fata, Jimmie E; Mori, Hidetoshi; Ewald, Andrew J; Zhang, Hui; Yao, Evelyn; Werb, Zena; Bissell, Mina J

    2006-10-03

    Transforming growth factor-{alpha} (TGF{alpha}) and fibroblast growth factor-7 (FGF7) exhibit distinct expression patterns in the mammary gland. Both factors signal through mitogen-activated kinase/extracellular regulated kinase-1,2 (MAPK{sup ERK1,2}); however, their unique and/or combined contributions to mammary morphogenesis have not been examined. In ex vivo mammary explants, we show that a sustained activation of MAPK{sup ERK1,2} for 1 h, induced by TGF{alpha}, was necessary and sufficient to initiate branching morphogenesis, whereas a transient activation (15 min) of MAPK{sup ERK1,2}, induced by FGF7, led to growth without branching. Unlike TGF{alpha}, FGF7 promoted sustained proliferation as well as ectopic localization of, and increase in, keratin-6 expressing cells. The response of the explants to FGF10 was similar to that to FGF7. Simultaneous stimulation by FGF7 and TGF{alpha} indicated that the FGF7-induced MAPK{sup ERK1,2} signaling and associated phenotypes were dominant: FGF7 may prevent branching by suppression of two necessary TGF{alpha}-induced morphogenetic effectors, matrix metalloproteinase-3 (MMP-3/stromelysin-1), and fibronectin. Our findings indicate that expression of morphogenetic effectors, proliferation, and cell-type decisions during mammary organoid morphogenesis are intimately dependent on the duration of activation of MAPK{sup ERK1,2} activation.

  7. Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification.

    Science.gov (United States)

    Kuzin, Boris A; Nikitina, Ekaterina A; Cherezov, Roman O; Vorontsova, Julia E; Slezinger, Mikhail S; Zatsepina, Olga G; Simonova, Olga B; Enikolopov, Grigori N; Savvateeva-Popova, Elena V

    2014-01-01

    Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response and long-term memory formation in Drosophila melanogaster. Oxidative stress was induced by low doses of X-ray irradiation of flies carrying hypomorphic mutation of spineless, mutation of CG5017, and their combination. To determine the sensitivity of these mutants to pharmacological modifiers of the irradiation effect, we irradiated flies growing on standard medium supplemented by radiosensitizer furazidin and radioprotector serotonin. The effects of irradiation were investigated by analyzing leg and antenna morphological structures and by using real-time PCR to measure mRNA expression levels for spineless, Cyp6g1 and Gst-theta genes. We also examined long-term memory in these mutants using conditioned courtship suppression paradigm. Our results show that the interaction of spineless and CG5017 is important for regulation of morphogenesis, long-term memory formation, and detoxification during oxidative stress. Since spineless and CG5017 are evolutionary conserved, these results must be considered when evaluating the risk of combining similar mutations in other organisms, including humans.

  8. Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification.

    Directory of Open Access Journals (Sweden)

    Boris A Kuzin

    Full Text Available Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response and long-term memory formation in Drosophila melanogaster. Oxidative stress was induced by low doses of X-ray irradiation of flies carrying hypomorphic mutation of spineless, mutation of CG5017, and their combination. To determine the sensitivity of these mutants to pharmacological modifiers of the irradiation effect, we irradiated flies growing on standard medium supplemented by radiosensitizer furazidin and radioprotector serotonin. The effects of irradiation were investigated by analyzing leg and antenna morphological structures and by using real-time PCR to measure mRNA expression levels for spineless, Cyp6g1 and Gst-theta genes. We also examined long-term memory in these mutants using conditioned courtship suppression paradigm. Our results show that the interaction of spineless and CG5017 is important for regulation of morphogenesis, long-term memory formation, and detoxification during oxidative stress. Since spineless and CG5017 are evolutionary conserved, these results must be considered when evaluating the risk of combining similar mutations in other organisms, including humans.

  9. Collective cell migration drives morphogenesis of the kidney nephron.

    Directory of Open Access Journals (Sweden)

    Aleksandr Vasilyev

    2009-01-01

    Full Text Available Tissue organization in epithelial organs is achieved during development by the combined processes of cell differentiation and morphogenetic cell movements. In the kidney, the nephron is the functional organ unit. Each nephron is an epithelial tubule that is subdivided into discrete segments with specific transport functions. Little is known about how nephron segments are defined or how segments acquire their distinctive morphology and cell shape. Using live, in vivo cell imaging of the forming zebrafish pronephric nephron, we found that the migration of fully differentiated epithelial cells accounts for both the final position of nephron segment boundaries and the characteristic convolution of the proximal tubule. Pronephric cells maintain adherens junctions and polarized apical brush border membranes while they migrate collectively. Individual tubule cells exhibit basal membrane protrusions in the direction of movement and appear to establish transient, phosphorylated Focal Adhesion Kinase-positive adhesions to the basement membrane. Cell migration continued in the presence of camptothecin, indicating that cell division does not drive migration. Lengthening of the nephron was, however, accompanied by an increase in tubule cell number, specifically in the most distal, ret1-positive nephron segment. The initiation of cell migration coincided with the onset of fluid flow in the pronephros. Complete blockade of pronephric fluid flow prevented cell migration and proximal nephron convolution. Selective blockade of proximal, filtration-driven fluid flow shifted the position of tubule convolution distally and revealed a role for cilia-driven fluid flow in persistent migration of distal nephron cells. We conclude that nephron morphogenesis is driven by fluid flow-dependent, collective epithelial cell migration within the confines of the tubule basement membrane. Our results establish intimate links between nephron function, fluid flow, and morphogenesis.

  10. Giga-voxel computational morphogenesis for structural design

    Science.gov (United States)

    Aage, Niels; Andreassen, Erik; Lazarov, Boyan S.; Sigmund, Ole

    2017-10-01

    In the design of industrial products ranging from hearing aids to automobiles and aeroplanes, material is distributed so as to maximize the performance and minimize the cost. Historically, human intuition and insight have driven the evolution of mechanical design, recently assisted by computer-aided design approaches. The computer-aided approach known as topology optimization enables unrestricted design freedom and shows great promise with regard to weight savings, but its applicability has so far been limited to the design of single components or simple structures, owing to the resolution limits of current optimization methods. Here we report a computational morphogenesis tool, implemented on a supercomputer, that produces designs with giga-voxel resolution—more than two orders of magnitude higher than previously reported. Such resolution provides insights into the optimal distribution of material within a structure that were hitherto unachievable owing to the challenges of scaling up existing modelling and optimization frameworks. As an example, we apply the tool to the design of the internal structure of a full-scale aeroplane wing. The optimized full-wing design has unprecedented structural detail at length scales ranging from tens of metres to millimetres and, intriguingly, shows remarkable similarity to naturally occurring bone structures in, for example, bird beaks. We estimate that our optimized design corresponds to a reduction in mass of 2-5 per cent compared to currently used aeroplane wing designs, which translates into a reduction in fuel consumption of about 40-200 tonnes per year per aeroplane. Our morphogenesis process is generally applicable, not only to mechanical design, but also to flow systems, antennas, nano-optics and micro-systems.

  11. BAF200 is required for heart morphogenesis and coronary artery development.

    Directory of Open Access Journals (Sweden)

    Lingjuan He

    Full Text Available ATP-dependent SWI/SNF chromatin remodeling complexes utilize ATP hydrolysis to non-covalently change nucleosome-DNA interactions and are essential in stem cell development, organogenesis, and tumorigenesis. Biochemical studies show that SWI/SNF in mammalian cells can be divided into two subcomplexes BAF and PBAF based on the subunit composition. ARID2 or BAF200 has been defined as an intrinsic subunit of PBAF complex. However, the function of BAF200 in vivo is not clear. To dissect the possible role of BAF200 in regulating embryogenesis and organ development, we generated BAF200 mutant mice and found they were embryonic lethal. BAF200 mutant embryos exhibited multiple cardiac defects including thin myocardium, ventricular septum defect, common atrioventricular valve, and double outlet right ventricle around E14.5. Moreover, we also detected reduced intramyocardial coronary arteries in BAF200 mutants, suggesting that BAF200 is required for proper migration and differentiation of subepicardial venous cells into arterial endothelial cells. Our work revealed that PBAF complex plays a critical role in heart morphogenesis and coronary artery angiogenesis.

  12. A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis

    Directory of Open Access Journals (Sweden)

    Mala Misra

    2016-08-01

    Full Text Available Localizing messenger RNAs at specific subcellular sites is a conserved mechanism for targeting the synthesis of cytoplasmic proteins to distinct subcellular domains, thereby generating the asymmetric protein distributions necessary for cellular and developmental polarity. However, the full range of transcripts that are asymmetrically distributed in specialized cell types, and the significance of their localization, especially in the nervous system, are not known. We used the EP-MS2 method, which combines EP transposon insertion with the MS2/MCP in vivo fluorescent labeling system, to screen for novel localized transcripts in polarized cells, focusing on the highly branched Drosophila class IV dendritic arborization neurons. Of a total of 541 lines screened, we identified 55 EP-MS2 insertions producing transcripts that were enriched in neuronal processes, particularly in dendrites. The 47 genes identified by these insertions encode molecularly diverse proteins, and are enriched for genes that function in neuronal development and physiology. RNAi-mediated knockdown confirmed roles for many of the candidate genes in dendrite morphogenesis. We propose that the transport of mRNAs encoded by these genes into the dendrites allows their expression to be regulated on a local scale during the dynamic developmental processes of dendrite outgrowth, branching, and/or remodeling.

  13. Automated Image Analysis of Lung Branching Morphogenesis from Microscopic Images of Fetal Rat Explants

    Science.gov (United States)

    Rodrigues, Pedro L.; Rodrigues, Nuno F.; Duque, Duarte; Granja, Sara; Correia-Pinto, Jorge; Vilaça, João L.

    2014-01-01

    Background. Regulating mechanisms of branching morphogenesis of fetal lung rat explants have been an essential tool for molecular research. This work presents a new methodology to accurately quantify the epithelial, outer contour, and peripheral airway buds of lung explants during cellular development from microscopic images. Methods. The outer contour was defined using an adaptive and multiscale threshold algorithm whose level was automatically calculated based on an entropy maximization criterion. The inner lung epithelium was defined by a clustering procedure that groups small image regions according to the minimum description length principle and local statistical properties. Finally, the number of peripheral buds was counted as the skeleton branched ends from a skeletonized image of the lung inner epithelia. Results. The time for lung branching morphometric analysis was reduced in 98% in contrast to the manual method. Best results were obtained in the first two days of cellular development, with lesser standard deviations. Nonsignificant differences were found between the automatic and manual results in all culture days. Conclusions. The proposed method introduces a series of advantages related to its intuitive use and accuracy, making the technique suitable to images with different lighting characteristics and allowing a reliable comparison between different researchers. PMID:25250057

  14. Automated Image Analysis of Lung Branching Morphogenesis from Microscopic Images of Fetal Rat Explants

    Directory of Open Access Journals (Sweden)

    Pedro L. Rodrigues

    2014-01-01

    Full Text Available Background. Regulating mechanisms of branching morphogenesis of fetal lung rat explants have been an essential tool for molecular research. This work presents a new methodology to accurately quantify the epithelial, outer contour, and peripheral airway buds of lung explants during cellular development from microscopic images. Methods. The outer contour was defined using an adaptive and multiscale threshold algorithm whose level was automatically calculated based on an entropy maximization criterion. The inner lung epithelium was defined by a clustering procedure that groups small image regions according to the minimum description length principle and local statistical properties. Finally, the number of peripheral buds was counted as the skeleton branched ends from a skeletonized image of the lung inner epithelia. Results. The time for lung branching morphometric analysis was reduced in 98% in contrast to the manual method. Best results were obtained in the first two days of cellular development, with lesser standard deviations. Nonsignificant differences were found between the automatic and manual results in all culture days. Conclusions. The proposed method introduces a series of advantages related to its intuitive use and accuracy, making the technique suitable to images with different lighting characteristics and allowing a reliable comparison between different researchers.

  15. Kidney branching morphogenesis under the control of a ligand–receptor-based Turing mechanism

    International Nuclear Information System (INIS)

    Menshykau, Denis; Iber, Dagmar

    2013-01-01

    The main signalling proteins that control early kidney branching have been defined. Yet the underlying mechanism is still elusive. We have previously shown that a Schnakenberg-type Turing mechanism can recapitulate the branching and protein expression patterns in wild-type and mutant lungs, but it is unclear whether this mechanism would extend to other branched organs that are regulated by other proteins. Here, we show that the glial cell line-derived neurotrophic factor–RET regulatory interaction gives rise to a Schnakenberg-type Turing model that reproduces the observed budding of the ureteric bud from the Wolffian duct, its invasion into the mesenchyme and the observed branching pattern. The model also recapitulates all relevant protein expression patterns in wild-type and mutant mice. The lung and kidney models are both based on a particular receptor–ligand interaction and require (1) cooperative binding of ligand and receptor, (2) a lower diffusion coefficient for the receptor than for the ligand and (3) an increase in the receptor concentration in response to receptor–ligand binding (by enhanced transcription, more recycling or similar). These conditions are met also by other receptor–ligand systems. We propose that ligand–receptor-based Turing patterns represent a general mechanism to control branching morphogenesis and other developmental processes. (paper)

  16. Hepatocyte growth factor signaling in intrapancreatic ductal cells drives pancreatic morphogenesis.

    Directory of Open Access Journals (Sweden)

    Ryan M Anderson

    Full Text Available In a forward genetic screen for regulators of pancreas development in zebrafish, we identified donut(s908 , a mutant which exhibits failed outgrowth of the exocrine pancreas. The s908 mutation leads to a leucine to arginine substitution in the ectodomain of the hepatocyte growth factor (HGF tyrosine kinase receptor, Met. This missense mutation impedes the proteolytic maturation of the receptor, its trafficking to the plasma membrane, and diminishes the phospho-activation of its kinase domain. Interestingly, during pancreatogenesis, met and its hgf ligands are expressed in pancreatic epithelia and mesenchyme, respectively. Although Met signaling elicits mitogenic and migratory responses in varied contexts, normal proliferation rates in donut mutant pancreata together with dysmorphic, mislocalized ductal cells suggest that met primarily functions motogenically in pancreatic tail formation. Treatment with PI3K and STAT3 inhibitors, but not with MAPK inhibitors, phenocopies the donut pancreatic defect, further indicating that Met signals through migratory pathways during pancreas development. Chimera analyses showed that Met-deficient cells were excluded from the duct, but not acinar, compartment in the pancreatic tail. Conversely, wild-type intrapancreatic duct and "tip cells" at the leading edge of the growing pancreas rescued the donut phenotype. Altogether, these results reveal a novel and essential role for HGF signaling in the intrapancreatic ducts during exocrine morphogenesis.

  17. EMMPRIN (basigin/CD147) is involved in the morphogenesis of tooth germ in mouse molars.

    Science.gov (United States)

    Xie, Ming; Jiao, Ting; Chen, Yuqin; Xu, Chun; Li, Jing; Jiang, Xinquan; Zhang, Fuqiang

    2010-05-01

    The pattern of gene expression for extracellular matrix metalloproteinase inducer (EMMPRIN) was revealed in the tooth germ of mouse mandibular molars using quantitative real-time PCR. In situ hybridization and immunohistochemical study demonstrated the characteristic distribution of EMMPRIN in the different stages of tooth germ development. To investigate the functional role played by EMMPRIN in tooth germ development, EMMPRIN siRNA interference approach was carried out in cultured mouse mandibles at embryonic day 11.0 (E11.0). The results showed that EMMPRIN siRNA-treated explants exhibited a marked growth inhibition of tooth germ compared to the control and scrambled siRNA-treated explants. Meanwhile, a significant increase in MT1-MMP mRNA expression and a reduction in MMP-2, MMP-3, MMP-9, MMP-13 and MT2-MMP mRNA expression were observed in the mouse mandibles following EMMPRIN abrogation. The current results indicate that EMMPRIN could thus be involved in the early stage of tooth germ development and morphogenesis, possibly by regulating the expression of MMP genes.

  18. Xyloglucan Deficiency Disrupts Microtubule Stability and Cellulose Biosynthesis in Arabidopsis, Altering Cell Growth and Morphogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Chaowen; Zhang, Tian; Zheng, Yunzhen; Cosgrove, Daniel J.; Anderson, Charles T.

    2015-11-02

    Xyloglucan constitutes most of the hemicellulose in eudicot primary cell walls and functions in cell wall structure and mechanics. Although Arabidopsis (Arabidopsis thaliana) xxt1 xxt2 mutants lacking detectable xyloglucan are viable, they display growth defects that are suggestive of alterations in wall integrity. To probe the mechanisms underlying these defects, we analyzed cellulose arrangement, microtubule patterning and dynamics, microtubule- and wall-integrity-related gene expression, and cellulose biosynthesis in xxt1 xxt2 plants. We found that cellulose is highly aligned in xxt1 xxt2 cell walls, that its three-dimensional distribution is altered, and that microtubule patterning and stability are aberrant in etiolated xxt1 xxt2 hypocotyls. We also found that the expression levels of microtubule-associated genes, such as MAP70-5 and CLASP, and receptor genes, such as HERK1 and WAK1, were changed in xxt1 xxt2 plants and that cellulose synthase motility is reduced in xxt1 xxt2 cells, corresponding with a reduction in cellulose content. Our results indicate that loss of xyloglucan affects both the stability of the microtubule cytoskeleton and the production and patterning of cellulose in primary cell walls. These findings establish, to our knowledge, new links between wall integrity, cytoskeletal dynamics, and wall synthesis in the regulation of plant morphogenesis.

  19. Functional Requirements for Heparan Sulfate Biosynthesis in Morphogenesis and Nervous System Development in C. elegans.

    Science.gov (United States)

    Blanchette, Cassandra R; Thackeray, Andrea; Perrat, Paola N; Hekimi, Siegfried; Bénard, Claire Y

    2017-01-01

    The regulation of cell migration is essential to animal development and physiology. Heparan sulfate proteoglycans shape the interactions of morphogens and guidance cues with their respective receptors to elicit appropriate cellular responses. Heparan sulfate proteoglycans consist of a protein core with attached heparan sulfate glycosaminoglycan chains, which are synthesized by glycosyltransferases of the exostosin (EXT) family. Abnormal HS chain synthesis results in pleiotropic consequences, including abnormal development and tumor formation. In humans, mutations in either of the exostosin genes EXT1 and EXT2 lead to osteosarcomas or multiple exostoses. Complete loss of any of the exostosin glycosyltransferases in mouse, fish, flies and worms leads to drastic morphogenetic defects and embryonic lethality. Here we identify and study previously unavailable viable hypomorphic mutations in the two C. elegans exostosin glycosyltransferases genes, rib-1 and rib-2. These partial loss-of-function mutations lead to a severe reduction of HS levels and result in profound but specific developmental defects, including abnormal cell and axonal migrations. We find that the expression pattern of the HS copolymerase is dynamic during embryonic and larval morphogenesis, and is sustained throughout life in specific cell types, consistent with HSPGs playing both developmental and post-developmental roles. Cell-type specific expression of the HS copolymerase shows that HS elongation is required in both the migrating neuron and neighboring cells to coordinate migration guidance. Our findings provide insights into general principles underlying HSPG function in development.

  20. Mechanical control of notochord morphogenesis by extra-embryonic tissues in mouse embryos.

    Science.gov (United States)

    Imuta, Yu; Koyama, Hiroshi; Shi, Dongbo; Eiraku, Mototsugu; Fujimori, Toshihiko; Sasaki, Hiroshi

    2014-05-01

    Mammalian embryos develop in coordination with extraembryonic tissues, which support embryonic development by implanting embryos into the uterus, supplying nutrition, providing a confined niche, and also providing patterning signals to embryos. Here, we show that in mouse embryos, the expansion of the amniotic cavity (AC), which is formed between embryonic and extraembryonic tissues, provides the mechanical forces required for a type of morphogenetic movement of the notochord known as convergent extension (CE) in which the cells converge to the midline and the tissue elongates along the antero-posterior (AP) axis. The notochord is stretched along the AP axis, and the expansion of the AC is required for CE. Both mathematical modeling and physical simulation showed that a rectangular morphology of the early notochord caused the application of anisotropic force along the AP axis to the notochord through the isotropic expansion of the AC. AC expansion acts upstream of planar cell polarity (PCP) signaling, which regulates CE movement. Our results highlight the importance of extraembryonic tissues as a source of the forces that control the morphogenesis of embryos. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. MET receptor tyrosine kinase controls dendritic complexity, spine morphogenesis, and glutamatergic synapse maturation in the hippocampus.

    Science.gov (United States)

    Qiu, Shenfeng; Lu, Zhongming; Levitt, Pat

    2014-12-03

    The MET receptor tyrosine kinase (RTK), implicated in risk for autism spectrum disorder (ASD) and in functional and structural circuit integrity in humans, is a temporally and spatially regulated receptor enriched in dorsal pallial-derived structures during mouse forebrain development. Here we report that loss or gain of function of MET in vitro or in vivo leads to changes, opposite in nature, in dendritic complexity, spine morphogenesis, and the timing of glutamatergic synapse maturation onto hippocampus CA1 neurons. Consistent with the morphological and biochemical changes, deletion of Met in mutant mice results in precocious maturation of excitatory synapse, as indicated by a reduction of the proportion of silent synapses, a faster GluN2A subunit switch, and an enhanced acquisition of AMPA receptors at synaptic sites. Thus, MET-mediated signaling appears to serve as a mechanism for controlling the timing of neuronal growth and functional maturation. These studies suggest that mistimed maturation of glutamatergic synapses leads to the aberrant neural circuits that may be associated with ASD risk. Copyright © 2014 the authors 0270-6474/14/3416166-14$15.00/0.

  2. Expression of Genes Involved in Drosophila Wing Morphogenesis and Vein Patterning Are Altered by Spaceflight

    Science.gov (United States)

    Parsons-Wingerter, Patricia A.; Hosamani, Ravikumar; Bhattacharya, Sharmila

    2015-01-01

    Imaginal wing discs of Drosophila melanogaster (fruit fly) defined during embryogenesis ultimately result in mature wings of stereotyped (specific) venation patterning. Major regulators of wing disc development are the epidermal growth factor receptor (EGF), Notch, Hedgehog (Hh), Wingless (Wg), and Dpp signaling pathways. Highly stereotyped vascular patterning is also characteristic of tissues in other organisms flown in space such as the mouse retina and leaves of Arabidopsis thaliana. Genetic and other adaptations of vascular patterning to space environmental factors have not yet been systematically quantified, despite widespread recognition of their critical importance for terrestrial and microgravity applications. Here we report changes in gene expression with space flight related to Drosophila wing morphogenesis and vein patterning. In addition, genetically modified phenotypes of increasingly abnormal ectopic wing venation in the Drosophila wing1 were analyzed by NASA's VESsel GENeration Analysis (VESGEN) software2. Our goal is to further develop insightful vascular mappings associated with bioinformatic dimensions of genetic or other molecular phenotypes for correlation with genetic and other molecular profiling relevant to NASA's GeneLab and other Space Biology exploration initiatives.

  3. Searching for biomarkers of developmental toxicity with microarrays: normal eye morphogenesis in rodent embryos

    International Nuclear Information System (INIS)

    Nemeth, Kimberly A.; Singh, Amar V.; Knudsen, Thomas B.

    2005-01-01

    Gene expression arrays reveal the potential linkage of altered gene expression with specific adverse effects leading to disease phenotypes. But how closely do microarray data reflect early physiological or pharmacological measures that predict toxic event(s)? To explore this issue, we have undertaken experiments in early mouse embryos exposed to various teratogens during neurulation stages with the aim of correlating large-scale changes in gene expression across the critical period during exposure. This study reports some of the large-scale changes in gene expression that can be detected in the optic rudiment of the developing mouse and rat embryo across the window of development during which the eye is exceedingly sensitive to teratogen-induced micro-/anophthalmia. Microarray analysis was performed on RNA from the headfold or ocular region at the optic vesicle and optic cup stages when the ocular primordium is enriched for Pax-6, a master control gene for eye morphogenesis. Statistical selection of differentially regulated genes and various clustering techniques identified groups of genes in upward or downward trajectories in the normal optic primordium during early eye development in mouse and rat species. We identified 165 genes with significant differential expression during eye development, and a smaller subset of 58 genes that showed a tight correlation between mouse-rat development. Significantly over-represented functional categories included fatty acid metabolism (up-regulated) and glycolysis (down-regulated). From studies such as these that benchmark large-scale gene expression during normal embryonic development, we may be able to identify the panel of biomarkers that best correlate with species differences and the risks for developmental toxicity

  4. Scribble is required for normal epithelial cell–cell contacts and lumen morphogenesis in the mammalian lung

    Science.gov (United States)

    Yates, Laura L.; Schnatwinkel, Carsten; Hazelwood, Lee; Chessum, Lauren; Paudyal, Anju; Hilton, Helen; Romero, M. Rosario; Wilde, Jonathan; Bogani, Debora; Sanderson, Jeremy; Formstone, Caroline; Murdoch, Jennifer N.; Niswander, Lee A.; Greenfield, Andy; Dean, Charlotte H.

    2013-01-01

    During lung development, proper epithelial cell arrangements are critical for the formation of an arborized network of tubes. Each tube requires a lumen, the diameter of which must be tightly regulated to enable optimal lung function. Lung branching and lumen morphogenesis require close epithelial cell–cell contacts that are maintained as a result of adherens junctions, tight junctions and by intact apical–basal (A/B) polarity. However, the molecular mechanisms that maintain epithelial cohesion and lumen diameter in the mammalian lung are unknown. Here we show that Scribble, a protein implicated in planar cell polarity (PCP) signalling, is necessary for normal lung morphogenesis. Lungs of the Scrib mouse mutant Circletail (Crc) are abnormally shaped with fewer airways, and these airways often lack a visible, ‘open’ lumen. Mechanistically we show that Scrib genetically interacts with the core PCP gene Vangl2 in the developing lung and that the distribution of PCP pathway proteins and Rho mediated cytoskeletal modification is perturbed in ScribCrc/Crc lungs. However A/B polarity, which is disrupted in Drosophila Scrib mutants, is largely unaffected. Notably, we find that Scrib mediates functions not attributed to other PCP proteins in the lung. Specifically, Scrib localises to both adherens and tight junctions of lung epithelia and knockdown of Scrib in lung explants and organotypic cultures leads to reduced cohesion of lung epithelial cells. Live imaging of Scrib knockdown lungs shows that Scrib does not affect bud bifurcation, as previously shown for the PCP protein Celsr1, but is required to maintain epithelial cohesion. To understand the mechanism leading to reduced cell–cell association, we show that Scrib associates with β-catenin in embryonic lung and the sub-cellular distribution of adherens and tight junction proteins is perturbed in mutant lung epithelia. Our data reveal that Scrib is required for normal lung epithelial organisation and lumen

  5. Microgravity is the experimentl basis for understanding of the peculiarities of plant morphogenesis in the gravitational field

    Science.gov (United States)

    Demkiv, O. T.; Kordyum, Ye. L.; Khorkavtsiv, Ya. D.; Tairbekov, M. G.

    Spiral growth of the gravisensitive protonema of Ceratodon purpureus moss is revealed in real microgravity during space flight. Caulonema differentiation with oblique cell partitions and deviation of an apical cell growth zone from the growth horizontal axis were shown to precede the stolon spiralization. The slope of subapical cell walls enables an apical cell to revolve on its long axis, overcome the substrate and gravity resistance, and become twisted. Investigations of C. purpureus, Burbula unguiculata and Physcomitrella patens protonema growth in the conditions of 1g, real and simulated microgravity (clinorotation) in darkness and under different light intensity and nutrient medium composition show that protonema morphogenesis is above all regulated by endogenous signals, action of which is concealed by gravity or light on the Earth.

  6. Colgajo de omento para tratamiento de dehiscencia de herida esternal Omental flap for management of sternal wound dehiscence

    Directory of Open Access Journals (Sweden)

    A. Pérez García

    2013-03-01

    Full Text Available La mediastinitis es una de las complicaciones más graves de la cirugía cardíaca. Aparece en el 0,5-5 % de las esternotomías y esta incidencia es mucho mayor en pacientes diabéticos, obesos, inmunodeprimidos, con enfermedad pulmonar obstructiva crónica (EPOC, etc. Presentamos el caso de una paciente diabética, obesa mórbida, que sufre mediastinitis tras doble by-pass coronario. Para la cobertura del defecto se empleó un colgajo de epiplon tunelizado transdiafragmático. El colgajo omental permite cubrir grandes defectos además de que posee capacidad antimicrobiana y favorece la revascularización tisular. Las características de este colgajo hacen que actualmente deba considerarse como primera elección en pacientes con grandes defectos esternales y trastornos de la inmunidad y la cicatrización.Mediastinitis is one of the most serious complications from cardiac surgery. It is reported to occur in 0'5-5 % of sternotomy incisions, and this incidence is much higher in diabetic patients, obese, immunocompromised, COPD, etc. We report a case of a diabetic and morbid obese woman suffering mediastinitis after double coronary bypass surgery. For the reconstruction a transdiaphragmatic tunnelled omental flap was used. The omentum is useful to cover large defects. It has antiinfective properties and promotes revascularization of neighbouring tissues. Omental flap can be a highly effective treatment for patients with large sternal wounds and immune disorders and wound healing disorders.

  7. Sternal Route More Effective than Tibial Route for Intraosseous Amiodarone Administration in a Swine Model of Ventricular Fibrillation.

    Science.gov (United States)

    Burgert, James M; Martinez, Andre; O'Sullivan, Mara; Blouin, Dawn; Long, Audrey; Johnson, Arthur D

    2018-01-01

    The pharmacokinetics of IO administered lipid soluble amiodarone during ventricular fibrillation (VF) with ongoing CPR are unknown. This study measured mean plasma concentration over 5 minutes, maximum plasma concentration (Cmax), and time to maximum concentration (Tmax) of amiodarone administered by the sternal IO (SIO), tibial IO (TIO), and IV routes in a swine model of VF with ongoing CPR. Twenty-one Yorkshire-cross swine were randomly assigned to three groups: SIO, TIO, and IV. Ventricular fibrillation was induced under general anesthesia. After 4 minutes in VF, 300 mg amiodarone was administered as indicated by group assignment. Serial blood specimens collected at 30, 60, 90, 120, 150, 180, 240, and 300 seconds were analyzed using high performance liquid chromatography with tandem mass spectrometry. The mean plasma concentration of IV amiodarone over 5 minutes was significantly higher than the TIO group at 60 seconds (P = 0.02) and 90 seconds (P = 0.017) post-injection. No significant differences in Cmax between the groups were found (P <0.05). The Tmax of amiodarone was significantly shorter in the SIO (99 secs) and IV (86 secs) groups compared to the TIO group (215 secs); P = 0.002 and P = 0.002, respectively. The SIO and IV routes of amiodarone administration were comparable. The TIO group took nearly three times longer to reach Tmax than the SIO and IV groups, likely indicating depot of lipid-soluble amiodarone in adipose-rich tibial yellow bone marrow. The SIO route was more effective than the TIO route for amiodarone delivery in a swine model of VF with ongoing CPR. Further investigations are necessary to determine if the kinetic differences found between the SIO and TIO routes in this study affect survival of VF in humans.

  8. Filling Knowledge Gaps for Mimivirus Entry, Uncoating, and Morphogenesis.

    Science.gov (United States)

    Andrade, Ana Cláudia Dos Santos Pereira; Rodrigues, Rodrigo Araújo Lima; Oliveira, Graziele Pereira; Andrade, Kétyllen Reis; Bonjardim, Cláudio Antônio; La Scola, Bernard; Kroon, Erna Geessien; Abrahão, Jônatas Santos

    2017-11-15

    Since the discovery of mimivirus, its unusual structural and genomic features have raised great interest in the study of its biology; however, many aspects concerning its replication cycle remain uncertain. In this study, extensive analyses of electron microscope images, as well as biological assay results, shed light on unclear points concerning the mimivirus replication cycle. We found that treatment with cytochalasin, a phagocytosis inhibitor, negatively impacted the incorporation of mimivirus particles by Acanthamoeba castellanii , causing a negative effect on viral growth in amoeba monolayers. Treatment of amoebas with bafilomicin significantly impacted mimivirus uncoating and replication. In conjunction with microscopic analyses, these data suggest that mimiviruses indeed depend on phagocytosis for entry into amoebas, and particle uncoating (and stargate opening) appears to be dependent on phagosome acidification. In-depth analyses of particle morphogenesis suggest that the mimivirus capsids are assembled from growing lamellar structures. Despite proposals from previous studies that genome acquisition occurs before the acquisition of fibrils, our results clearly demonstrate that the genome and fibrils can be acquired simultaneously. Our data suggest the existence of a specific area surrounding the core of the viral factory where particles acquire the surface fibrils. Furthermore, we reinforce the concept that defective particles can be formed even in the absence of virophages. Our work provides new information about unexplored steps in the life cycle of mimivirus. IMPORTANCE Investigating the viral life cycle is essential to a better understanding of virus biology. The combination of biological assays and microscopic images allows a clear view of the biological features of viruses. Since the discovery of mimivirus, many studies have been conducted to characterize its replication cycle, but many knowledge gaps remain to be filled. In this study, we conducted a

  9. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  10. Embryonic Heart Morphogenesis from Confocal Microscopy Imaging and Automatic Segmentation

    Directory of Open Access Journals (Sweden)

    Hongda Mao

    2013-01-01

    Full Text Available Embryonic heart morphogenesis (EHM is a complex and dynamic process where the heart transforms from a single tube into a four-chambered pump. This process is of great biological and clinical interest but is still poorly understood for two main reasons. On the one hand, the existing imaging modalities for investigating EHM suffered from either limited penetration depth or limited spatial resolution. On the other hand, current works typically adopted manual segmentation, which was tedious, subjective, and time consuming considering the complexity of developing heart geometry and the large size of images. In this paper, we propose to utilize confocal microscopy imaging with tissue optical immersion clearing technique to image the heart at different stages of development for EHM study. The imaging method is able to produce high spatial resolution images and achieve large penetration depth at the same time. Furthermore, we propose a novel convex active contour model for automatic image segmentation. The model has the ability to deal with intensity fall-off in depth which is characterized by confocal microscopy images. We acquired the images of embryonic quail hearts from day 6 to day 14 of incubation for EHM study. The experimental results were promising and provided us with an insight view of early heart growth pattern and also paved the road for data-driven heart growth modeling.

  11. The green seaweed Ulva: A model system to study morphogenesis

    Directory of Open Access Journals (Sweden)

    Thomas eWichard

    2015-02-01

    Full Text Available Green macroalgae, mostly represented by the Ulvophyceae, the main multicellular branch of the Chlorophyceae, constitute important primary producers of marine and brackish coastal ecosystems. Ulva or sea lettuce species are some of the most abundant representatives, being ubiquitous in coastal benthic communities around the world. Nonetheless the genus also remains largely understudied. This review highlights Ulva as an exciting novel model organism for studies of algal growth, development and morphogenesis as well as mutualistic interactions. The key reasons that Ulva is potentially such a good model system are: (i patterns of Ulva development can drive ecologically important events, such as the increasing number of green tides observed worldwide as a result of eutrophication of coastal waters, (ii Ulva growth is symbiotic, with proper development requiring close association with bacterial epiphytes, (iii Ulva is extremely developmentally plastic, which can shed light on the transition from simple to complex multicellularity and (iv Ulva will provide additional information about the evolution of the green lineage.

  12. Modeling the morphogenesis of brine channels in sea ice.

    Science.gov (United States)

    Kutschan, B; Morawetz, K; Gemming, S

    2010-03-01

    Brine channels are formed in sea ice under certain constraints and represent a habitat of different microorganisms. The complex system depends on a number of various quantities as salinity, density, pH value, or temperature. Each quantity governs the process of brine channel formation. There exists a strong link between bulk salinity and the presence of brine drainage channels in growing ice with respect to both the horizontal and vertical planes. We develop a suitable phenomenological model for the formation of brine channels both referring to the Ginzburg-Landau theory of phase transitions as well as to the chemical basis of morphogenesis according to Turing. It is possible to conclude from the critical wave number on the size of the structure and the critical parameters. The theoretically deduced transition rates have the same magnitude as the experimental values. The model creates channels of similar size as observed experimentally. An extension of the model toward channels with different sizes is possible. The microstructure of ice determines the albedo feedback and plays therefore an important role for large-scale global circulation models.

  13. The effect of fluorescent nanodiamonds on neuronal survival and morphogenesis.

    Science.gov (United States)

    Huang, Yung-An; Kao, Chun-Wei; Liu, Kuang-Kai; Huang, Hou-Syun; Chiang, Ming-Han; Soo, Ching-Ren; Chang, Huan-Cheng; Chiu, Tzai-Wen; Chao, Jui-I; Hwang, Eric

    2014-11-05

    Nanodiamond (ND) has emerged as a promising carbon nanomaterial for therapeutic applications. In previous studies, ND has been reported to have outstanding biocompatibility and high uptake rate in various cell types. ND containing nitrogen-vacancy centers exhibit fluorescence property is called fluorescent nanodiamond (FND), and has been applied for bio-labeling agent. However, the influence and application of FND on the nervous system remain elusive. In order to study the compatibility of FND on the nervous system, neurons treated with FNDs in vitro and in vivo were examined. FND did not induce cytotoxicity in primary neurons from either central (CNS) or peripheral nervous system (PNS); neither did intracranial injection of FND affect animal behavior. The neuronal uptake of FNDs was confirmed using flow cytometry and confocal microscopy. However, FND caused a concentration-dependent decrease in neurite length in both CNS and PNS neurons. Time-lapse live cell imaging showed that the reduction of neurite length was due to the spatial hindrance of FND on advancing axonal growth cone. These findings demonstrate that FNDs exhibit low neuronal toxicity but interfere with neuronal morphogenesis, and should be taken into consideration when applications involve actively growing neurites (e.g. nerve regeneration).

  14. The effect of fluorescent nanodiamonds on neuronal survival and morphogenesis

    Science.gov (United States)

    Huang, Yung-An; Kao, Chun-Wei; Liu, Kuang-Kai; Huang, Hou-Syun; Chiang, Ming-Han; Soo, Ching-Ren; Chang, Huan-Cheng; Chiu, Tzai-Wen; Chao, Jui-I.; Hwang, Eric

    2014-11-01

    Nanodiamond (ND) has emerged as a promising carbon nanomaterial for therapeutic applications. In previous studies, ND has been reported to have outstanding biocompatibility and high uptake rate in various cell types. ND containing nitrogen-vacancy centers exhibit fluorescence property is called fluorescent nanodiamond (FND), and has been applied for bio-labeling agent. However, the influence and application of FND on the nervous system remain elusive. In order to study the compatibility of FND on the nervous system, neurons treated with FNDs in vitro and in vivo were examined. FND did not induce cytotoxicity in primary neurons from either central (CNS) or peripheral nervous system (PNS); neither did intracranial injection of FND affect animal behavior. The neuronal uptake of FNDs was confirmed using flow cytometry and confocal microscopy. However, FND caused a concentration-dependent decrease in neurite length in both CNS and PNS neurons. Time-lapse live cell imaging showed that the reduction of neurite length was due to the spatial hindrance of FND on advancing axonal growth cone. These findings demonstrate that FNDs exhibit low neuronal toxicity but interfere with neuronal morphogenesis, and should be taken into consideration when applications involve actively growing neurites (e.g. nerve regeneration).

  15. Study on Seed Morphogenesis of Orobanchaceae in Taiwan

    Directory of Open Access Journals (Sweden)

    Jao-Shien Chen

    2011-11-01

    Full Text Available Seed morphogenesis of Orobanchaceae was not completely investigated previously. Here, we observed seed development of Orobanchaceous species in Taiwan using light and scanning electron microscopies. Results indicated that seeds of Aeginetia indica, Boschniakia himalaica, and Orobanche caerulescens all consisted of embryo, endosperm and testa. Ontogeny of the embryo in A. indica was Solanad type, while in both B. himalaica and O. caerulescens was Onagrad type. The mature embryos of the three species lacked embryonic organs, and their endosperm development was the cellular type and, at maturity, appeared as several cell layers of storage tissue. Ontogeny of the testa was all non-multiplicative, with the residues of the outermost cell layer and reticulately-thickened secondary walls of its cells at maturity. Mature seeds of A. indica and O. caerulescens were ovate whereas those of B. himalaica were oblate. As for Christisonia hookeri, due to lack of samples, only the cellular-typed endosperm was determined. The comparative development of Orobanchaceous seeds was discussed.

  16. Morphogenesis of Mammary Glands in Buffalo (Bubalus bubalis

    Directory of Open Access Journals (Sweden)

    Amit Challana

    2014-01-01

    Full Text Available The present research was elucidated on the morphogenesis of mammary gland of buffalo during prenatal development. Total of 16 foetuses ranging from 1.2 cm (34 days to 108 cm CVRL (curved crown rump length (317 days were used for study. The study revealed that mammary line was first observed at 1.2 cm CVRL (34 days, mammary hillock at 1.7 cm (37 days, and mammary bud at 2.6 cm CVRL (41 days foetuses. Epidermal cone was found at 6.7 cm CVRL (58 days whereas primary and secondary ducts were observed at 7.4 cm CVRL (62 days and 15 cm CVRL (96 days, respectively. Connective tissue whorls were reported at 18.2 cm CVRL (110 days and internal elastic lamina and muscle layers at 24.1 cm CVRL (129 days. Lobules were observed at 29.3 cm CVRL (140 days, rosette of furstenberg at 39.5 cm CVRL (163 days, and keratin plug at 45.5 cm CVRL (176 days foetus. Primordia of sweat and sebaceous glands around hair follicle were seen at 21.2 cm CVRL (122 days of foetal life. Differentiation of all the skin layers along with cornification was observed at 69 cm (229 days in group III foetuses.

  17. Aquaporin 2 promotes cell migration and epithelial morphogenesis.

    Science.gov (United States)

    Chen, Ying; Rice, William; Gu, Zhizhan; Li, Jian; Huang, Jianmin; Brenner, Michael B; Van Hoek, Alfred; Xiong, Jianping; Gundersen, Gregg G; Norman, Jim C; Hsu, Victor W; Fenton, Robert A; Brown, Dennis; Lu, Hua A Jenny

    2012-09-01

    The aquaporin 2 (AQP2) water channel, expressed in kidney collecting ducts, contributes critically to water homeostasis in mammals. Animals lacking or having significantly reduced levels of AQP2, however, have not only urinary concentrating abnormalities but also renal tubular defects that lead to neonatal mortality from renal failure. Here, we show that AQP2 is not only a water channel but also an integrin-binding membrane protein that promotes cell migration and epithelial morphogenesis. AQP2 expression modulates the trafficking and internalization of integrin β1, facilitating its turnover at focal adhesions. In vitro, disturbing the interaction between AQP2 and integrin β1 by mutating the RGD motif led to reduced endocytosis, retention of integrin β1 at the cell surface, and defective cell migration and tubulogenesis. Similarly, in vivo, AQP2-null mice exhibited significant retention of integrin β1 at the basolateral membrane and had tubular abnormalities. In summary, these data suggest that the water channel AQP2 interacts with integrins to promote renal epithelial cell migration, contributing to the structural and functional integrity of the mammalian kidney.

  18. Scintigraphic imaging with technetium-99M-labelled ceftizoxime is a reliable technique for the diagnosis of deep sternal wound infection in rats

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Paulo Henrique Nogueira; Diniz, Simone Odilia Fernandes; Cardoso, Valbert Nascimento; Tarabal, Bernardo; Takenaka, Isabella; Braga, Otavio; Vidigal, Paula Vieira Teixeira; Gelape, Claudio Leo; Araujo, Ivana Duval, E-mail: phnc@uol.com.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

    2015-07-01

    Purpose: to evaluate whether scintigraphy with technetium-99m-labeled ceftizoxime ({sup 99m}Tc-CFT) can differentiate mediastinitis from aseptic inflammation associated with sternotomy. Methods: twenty female Wistar rats were randomly distributed into four groups: S (control) -partial upper median sternotomy with no treatment; SW (control) - sternotomy and treatment of sternal wounds with bone wax; SB - sternotomy and infection with Staphylococcus aureus; SWB - sternotomy with bone wax treatment and bacterial infection. Scintigraphy with {sup 99m}Tc-CFT was performed eight days after surgery and images were collected 210 and 360 min after infusion of the radiopharmaceutical. Results: no animals exhibited clinical signs of wound infection at the end of the experiment, although histological data verified acute inflammatory response in those experimentally infected with bacteria. Scintigraphic images revealed that tropism of {sup 99m}Tc-CFT to infected sternums was greater than to their non-infected counterparts. Mean counts of radioactivity in bacteria-infected sternal regions (SB and SWB) were significantly higher (p = 0.0007) than those of the respective controls (S and SW).Conclusion: scintigraphy with technetium-99m-labeled ceftizoxime is a method that can potentially detect infection post sternotomy and differentiate from aseptic inflammation in animals experimentally inoculated with S. aureus (author)

  19. Impact of vacuum-assisted closure (VAC) therapy on clinical outcomes of patients with sternal wound infections: a meta-analysis of non-randomized studies.

    Science.gov (United States)

    Falagas, Matthew E; Tansarli, Giannoula S; Kapaskelis, Anastasios; Vardakas, Konstantinos Z

    2013-01-01

    To examine the impact of VAC therapy on mortality of patients with sternal wound infections after cardiothoracic surgery. Controversial results regarding mortality of patients with sternal wound infections were published. We performed a systematic search in PubMed and Scopus. Mortality was the primary outcome of the meta-analysis. Recurrences, complications and length of stay were secondary outcomes. Twenty-two retrospective studies including 2467 patients were eligible for inclusion. Patients treated with VAC had significantly lower mortality compared to those treated without VAC [2233 patients, RR = 0.40, (95% CI 0.28, 0.57)]. This finding was consistent regardless of the study design, the exclusion of studies with positive findings, the criteria for establishment of the compared groups, the time of mortality assessment or the type of infections under study, provided that adequate data was available. VAC therapy was associated with fewer recurrences (RR = 0.34, 95% CI: 0.19-0.59). The meta-analysis did not show any difference in the length of stay (RR = -2.25, 95% CI: -7.52-3.02). VAC therapy was associated with lower mortality than other surgical techniques in retrospective cohorts of patients with DSWIs following cardiothoracic surgery.

  20. Nanoscale morphogenesis of nylon-sputtered plasma polymer particles

    Science.gov (United States)

    Choukourov, Andrei; Shelemin, Artem; Pleskunov, Pavel; Nikitin, Daniil; Khalakhan, Ivan; Hanuš, Jan

    2018-05-01

    Sub-micron polymer particles are highly important in various fields including astrophysics, thermonuclear fusion and nanomedicine. Plasma polymerization offers the possibility to produce particles with tailor-made size, crosslink density and chemical composition to meet the requirements of a particular application. However, the mechanism of nucleation and growth of plasma polymer particles as well as diversity of their morphology remain far from being clear. Here, we prepared nitrogen-containing plasma polymer particles by rf magnetron sputtering of nylon in a gas aggregation cluster source with variable length. The method allowed the production of particles with roughly constant chemical composition and number density but with the mean size changing from 80 to 320 nm. Atomic Force Microscopy with super-sharp probes was applied to study the evolution of the particle surface topography as they grow in size. Height–height correlation and power spectral density functions were obtained to quantify the roughness exponent α  =  0.78, the growth exponent β  =  0.35, and the dynamic exponent 1/z  =  0.50. The set of critical exponents indicates that the particle surface evolves in a self-affine mode and the overall particle growth is caused by the accretion of polymer-forming species from the gas phase and not by coagulation. Redistribution of the incoming material over the surface coupled with the inhomogeneous distribution of inner stress is suggested as the main factor that determines the morphogenesis of the plasma polymer particles.

  1. Re-growth, morphogenesis and differentiation during starfish arm regeneration

    KAUST Repository

    Khadra, Yousra Ben

    2015-06-25

    The red starfish Echinaster sepositus is an excellent model for studying arm regeneration processes following traumatic amputation. The initial repair phase was described in a previous paper in terms of the early cicatrisation phenomena, and tissue and cell involvement. In this work we attempt to provide a further comprehensive description of the later regenerative stages in this species. Here we present the results of a detailed microscopic and submicroscopic investigation of the long regenerative phase, which can be subdivided into two sub-phases: early and advanced regenerative phases. The early regenerative phase (1-6 weeks p.a.) is characterized by tissue rearrangement, morphogenetic processes and initial differentiation events (mainly neurogenesis and skeletogenesis). The advanced regenerative phase (after 6 weeks p.a.) is characterized by further differentiation processes (early myogenesis), and obvious morphogenesis and re-growth of the regenerate. As in other starfish, the regenerative process in E. sepositus is relatively slow in comparison with that of crinoids and many ophiuroids, which is usually interpreted as resulting mainly from size-related aspects and of the more conspicuous involvement of morphallactic processes. Light and electron microscopy analyses suggest that some of the amputated structures, such as muscles, are not able to replace their missing parts by directly regrowing them from the remaining tissues, whereas others tissues, such as the skeleton and the radial nerve cord, appear to undergo direct re-growth. The overall process is in agreement with the distalization-intercalation model proposed by Agata and co-workers (1). Further experiments are needed to confirm this hypothesis. This article is protected by copyright. All rights reserved.

  2. A spatially-averaged mathematical model of kidney branching morphogenesis

    KAUST Repository

    Zubkov, V.S.

    2015-08-01

    © 2015 Published by Elsevier Ltd. Kidney development is initiated by the outgrowth of an epithelial ureteric bud into a population of mesenchymal cells. Reciprocal morphogenetic responses between these two populations generate a highly branched epithelial ureteric tree with the mesenchyme differentiating into nephrons, the functional units of the kidney. While we understand some of the mechanisms involved, current knowledge fails to explain the variability of organ sizes and nephron endowment in mice and humans. Here we present a spatially-averaged mathematical model of kidney morphogenesis in which the growth of the two key populations is described by a system of time-dependant ordinary differential equations. We assume that branching is symmetric and is invoked when the number of epithelial cells per tip reaches a threshold value. This process continues until the number of mesenchymal cells falls below a critical value that triggers cessation of branching. The mathematical model and its predictions are validated against experimentally quantified C57Bl6 mouse embryonic kidneys. Numerical simulations are performed to determine how the final number of branches changes as key system parameters are varied (such as the growth rate of tip cells, mesenchyme cells, or component cell population exit rate). Our results predict that the developing kidney responds differently to loss of cap and tip cells. They also indicate that the final number of kidney branches is less sensitive to changes in the growth rate of the ureteric tip cells than to changes in the growth rate of the mesenchymal cells. By inference, increasing the growth rate of mesenchymal cells should maximise branch number. Our model also provides a framework for predicting the branching outcome when ureteric tip or mesenchyme cells change behaviour in response to different genetic or environmental developmental stresses.

  3. Pancreatic morphogenesis and extracellular matrix organization during rat development.

    Science.gov (United States)

    Hisaoka, M; Haratake, J; Hashimoto, H

    1993-07-01

    pancreas, especially in the branching epithelial morphogenesis, and the major alterations appeared prior to distinct acinar cell differentiation.

  4. A spatially-averaged mathematical model of kidney branching morphogenesis

    KAUST Repository

    Zubkov, V.S.; Combes, A.N.; Short, K.M.; Lefevre, J.; Hamilton, N.A.; Smyth, I.M.; Little, M.H.; Byrne, H.M.

    2015-01-01

    © 2015 Published by Elsevier Ltd. Kidney development is initiated by the outgrowth of an epithelial ureteric bud into a population of mesenchymal cells. Reciprocal morphogenetic responses between these two populations generate a highly branched epithelial ureteric tree with the mesenchyme differentiating into nephrons, the functional units of the kidney. While we understand some of the mechanisms involved, current knowledge fails to explain the variability of organ sizes and nephron endowment in mice and humans. Here we present a spatially-averaged mathematical model of kidney morphogenesis in which the growth of the two key populations is described by a system of time-dependant ordinary differential equations. We assume that branching is symmetric and is invoked when the number of epithelial cells per tip reaches a threshold value. This process continues until the number of mesenchymal cells falls below a critical value that triggers cessation of branching. The mathematical model and its predictions are validated against experimentally quantified C57Bl6 mouse embryonic kidneys. Numerical simulations are performed to determine how the final number of branches changes as key system parameters are varied (such as the growth rate of tip cells, mesenchyme cells, or component cell population exit rate). Our results predict that the developing kidney responds differently to loss of cap and tip cells. They also indicate that the final number of kidney branches is less sensitive to changes in the growth rate of the ureteric tip cells than to changes in the growth rate of the mesenchymal cells. By inference, increasing the growth rate of mesenchymal cells should maximise branch number. Our model also provides a framework for predicting the branching outcome when ureteric tip or mesenchyme cells change behaviour in response to different genetic or environmental developmental stresses.

  5. A low-density culture method of cerebellar granule neurons with paracrine support applicable for the study of neuronal morphogenesis.

    Science.gov (United States)

    Kubota, Kenta; Seno, Takeshi; Konishi, Yoshiyuki

    2013-11-20

    Cerebellar granule neuronal cultures have been used to study the molecular mechanisms underlying neuronal functions, including neuronal morphogenesis. However, a limitation of this system is the difficulty to analyze isolated neurons because these are required to be maintained at a high density. Therefore, in the present study, we aimed to develop a simple and cost-effective method for culturing low-density cerebellar granule neurons. Cerebellar granule cells at two different densities (low- and high-density) were co-cultivated in order for the low-density culture to be supported by the paracrine signals from the high-density culture. This method enabled morphology analysis of isolated cerebellar granule neurons without astrocytic feeder cultures or supplements such as B27. Using this method, we investigated the function of a polarity factor. Studies using hippocampal neurons suggested that glycogen synthase kinase-3 (GSK-3) is an essential regulator of neuronal polarity, and inhibition of GSK-3 results in the formation of multiple axons. Pharmacological inhibitors for GSK-3 (6-bromoindirubin-3'-oxime and lithium chloride) did not cause the formation of multiple axons of cerebellar granule neurons but significantly reduced their length. Consistent results were obtained by introducing kinase-dead form of GSK-3 beta (K85A). These results indicated that GSK-3 is not directly involved in the control of neuronal polarity in cerebellar granule neurons. Overall, this study provides a simple method for culturing low-density cerebellar granule neurons and insights in to the neuronal-type dependent function of GSK-3 in neuronal morphogenesis. © 2013 Elsevier B.V. All rights reserved.

  6. Sox11 is required to maintain proper levels of Hedgehog signaling during vertebrate ocular morphogenesis.

    Directory of Open Access Journals (Sweden)

    Lakshmi Pillai-Kastoori

    2014-07-01

    Full Text Available Ocular coloboma is a sight-threatening malformation caused by failure of the choroid fissure to close during morphogenesis of the eye, and is frequently associated with additional anomalies, including microphthalmia and cataracts. Although Hedgehog signaling is known to play a critical role in choroid fissure closure, genetic regulation of this pathway remains poorly understood. Here, we show that the transcription factor Sox11 is required to maintain specific levels of Hedgehog signaling during ocular development. Sox11-deficient zebrafish embryos displayed delayed and abnormal lens formation, coloboma, and a specific reduction in rod photoreceptors, all of which could be rescued by treatment with the Hedgehog pathway inhibitor cyclopamine. We further demonstrate that the elevated Hedgehog signaling in Sox11-deficient zebrafish was caused by a large increase in shha transcription; indeed, suppressing Shha expression rescued the ocular phenotypes of sox11 morphants. Conversely, over-expression of sox11 induced cyclopia, a phenotype consistent with reduced levels of Sonic hedgehog. We screened DNA samples from 79 patients with microphthalmia, anophthalmia, or coloboma (MAC and identified two novel heterozygous SOX11 variants in individuals with coloboma. In contrast to wild type human SOX11 mRNA, mRNA containing either variant failed to rescue the lens and coloboma phenotypes of Sox11-deficient zebrafish, and both exhibited significantly reduced transactivation ability in a luciferase reporter assay. Moreover, decreased gene dosage from a segmental deletion encompassing the SOX11 locus resulted in microphthalmia and related ocular phenotypes. Therefore, our study reveals a novel role for Sox11 in controlling Hedgehog signaling, and suggests that SOX11 variants contribute to pediatric eye disorders.

  7. Three-dimensional endothelial cell morphogenesis under controlled ion release from copper-doped phosphate glass.

    Science.gov (United States)

    Stähli, Christoph; James-Bhasin, Mark; Nazhat, Showan N

    2015-02-28

    Copper ions represent a promising angiogenic agent but are associated with cytotoxicity at elevated concentrations. Phosphate-based glasses (PGs) exhibit adjustable dissolution properties and allow for controlled ion release. This study examined the formation of capillary-like networks by SVEC4-10 endothelial cells (ECs) seeded in a three-dimensional (3D) type I collagen hydrogel matrix mixed with PG particles of the formulation 50P2O5-30CaO-(20-x)Na2O-xCuO (x=0 and 10 mol%). Copper and total phosphorus release decreased over time and was more sustained in the case of 10% CuO PG. Moreover, increasing the concentration of 10% CuO PG in collagen substantially delayed dissolution along with preferential release of copper. A 3D morphometric characterization method based on confocal laser scanning microscopy image stacks was developed in order to quantify EC network length, connectivity and branching. Network length was initially reduced in a concentration-dependent fashion by 10% CuO PG and, to a lesser extent, by 0% CuO PG, but reached values identical to the non-PG control by day 5 in culture. This reduction was attributed to a PG-mediated decrease in cell metabolic activity while cell proliferation as well as network connectivity and branching were independent of PG content. Gene expression of matrix metalloproteinases (MMP)-1 and -2 was up-regulated by PGs, indicating that MMPs did not play a critical role in network growth. The relationship between ion release and EC morphogenesis in 3D provided in this study is expected to contribute to an ultimately successful pro-angiogenic application of CuO-doped PGs. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Elizabeth J Polvi

    2016-10-01

    Full Text Available Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which

  9. Obtaining plant Miscanthus sacchariflorus (Maxim. Hack and Miscanthus sinensis Andersson in vitro culture by indirect morphogenesis

    Directory of Open Access Journals (Sweden)

    С. М. Гонтаренко

    2017-03-01

    Full Text Available Purpose. To obtain Miscanthus sacchariflorus (Maxim. Hack and Miscanthus sinensis Andersson in vitro culture by indirect morphogenesis. Methods. Biotechnological procedures, mathematical and statistical analyses. Results. Composition of nutrient medium was developed intended for induction of callusogenesis from Miscanthus seeds with a poor germination and viability of seedlings – Murashige and Skoog (MS medium was modified for the amount of macroelements (half-dose that was supplemented with amino acids (300 mg/l of glutamic acid, 50 mg/l of aspartic acid, 5 mg/l of tyrosine, 3 mg/l of arginine, 2 mg/l of hydroxyproline and plant growth regulators [2,5 mg/l of 2.4D (2.4-Dichlorophenoxyacetic acid, 0,6 mg/l of BAP (6-Benzyl-aminopurine and 0,3 mg/l of ABA (Abscisic acid]. Composition of nutrient medium was developed for regeneration of microplants from callus – agar MS medium was modified for the amount of macroelements (half-dose supplemented with vitamins: 10 mg/l of thiaminum, 1,0 mg/l of pyridoxine, 1,0 mg/l of nicotinic acid (by White, 1,0 mg/l of ascorbic acid, 250 mg/l of glutamic acid, 2,0 mg/l of BAP, 0,3 mg/l of NAA (Naphthaleneacetic acid. On this medium, 100% regeneration of M. sacchariflorus (Maxim. Hack and 50% regeneration of M. sinensis Andersson was obtained. Due to media modification aimed at initiating callusogenesis and microplants regeneration, reproduction factor of M. sinensis was increased 20 times at the average, M. sacchariflorus – 35–40 times. Conclusions. Plants of M. sacchariflorus (Maxim. Hack and M. sinensis Andersson were obtained in vitro culture by initiation of callusogenes and microplants regeneration from the Miscanthus seeds with poor germination and viability on nutrient media of certain composition.

  10. Supplementary Material for: A global sensitivity analysis approach for morphogenesis models

    KAUST Repository

    Boas, Sonja

    2015-01-01

    Abstract Background Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand the relation between the uncertainty in the input and the output of such ‘black-box’ models, giving rise to the need for sensitivity analysis tools. In this paper, we introduce a workflow for a global sensitivity analysis approach to study the impact of single parameters and the interactions between them on the output of morphogenesis models. Results To demonstrate the workflow, we used a published, well-studied model of vascular morphogenesis. The parameters of this cellular Potts model (CPM) represent cell properties and behaviors that drive the mechanisms of angiogenic sprouting. The global sensitivity analysis correctly identified the dominant parameters in the model, consistent with previous studies. Additionally, the analysis provided information on the relative impact of single parameters and of interactions between them. This is very relevant because interactions of parameters impede the experimental verification of the predicted effect of single parameters. The parameter interactions, although of low impact, provided also new insights in the mechanisms of in silico sprouting. Finally, the analysis indicated that the model could be reduced by one parameter. Conclusions We propose global sensitivity analysis as an alternative approach to study the mechanisms of morphogenesis. Comparison of the ranking of the impact of the model parameters to knowledge derived from experimental data and from manipulation experiments can help to falsify models and to find the operand mechanisms in morphogenesis. The workflow is applicable to all ‘black-box’ models, including high-throughput in vitro models in which output measures are affected by a set of experimental perturbations.

  11. The case for applying tissue engineering methodologies to instruct human organoid morphogenesis.

    Science.gov (United States)

    Marti-Figueroa, Carlos R; Ashton, Randolph S

    2017-05-01

    Three-dimensional organoids derived from human pluripotent stem cell (hPSC) derivatives have become widely used in vitro models for studying development and disease. Their ability to recapitulate facets of normal human development during in vitro morphogenesis produces tissue structures with unprecedented biomimicry. Current organoid derivation protocols primarily rely on spontaneous morphogenesis processes to occur within 3-D spherical cell aggregates with minimal to no exogenous control. This yields organoids containing microscale regions of biomimetic tissues, but at the macroscale (i.e. 100's of microns to millimeters), the organoids' morphology, cytoarchitecture, and cellular composition are non-biomimetic and variable. The current lack of control over in vitro organoid morphogenesis at the microscale induces aberrations at the macroscale, which impedes realization of the technology's potential to reproducibly form anatomically correct human tissue units that could serve as optimal human in vitro models and even transplants. Here, we review tissue engineering methodologies that could be used to develop powerful approaches for instructing multiscale, 3-D human organoid morphogenesis. Such technological mergers are critically needed to harness organoid morphogenesis as a tool for engineering functional human tissues with biomimetic anatomy and physiology. Human PSC-derived 3-D organoids are revolutionizing the biomedical sciences. They enable the study of development and disease within patient-specific genetic backgrounds and unprecedented biomimetic tissue microenvironments. However, their uncontrolled, spontaneous morphogenesis at the microscale yields inconsistences in macroscale organoid morphology, cytoarchitecture, and cellular composition that limits their standardization and application. Integration of tissue engineering methods with organoid derivation protocols could allow us to harness their potential by instructing standardized in vitro morphogenesis

  12. Ultrasound of Sternal Fracture

    Directory of Open Access Journals (Sweden)

    Shadi Lahham

    2015-12-01

    Full Text Available A 61-year-old female was brought in by ambulance after being the restrained driver of a head-on motor vehicle collision at 40MPH. There was positive airbag deployment and intrusion from the other vehicle. During workup, the patient complained of midline chest pain, and left chest wall pain. The patient was not in acute respiratory distress, and had the following vital signs: temperature 37°C, heart rate 84, blood pressure of 150/64, respiratory rate 18, and oxygen saturation of 97% on two liters of oxygen. On physical exam, breath sounds were heard bilaterally, with no acute cardiopulmonary issues identified. A bruise was identified on the lower abdomen, which was thought to be a potential seatbelt sign. A focused assessment with sonography for trauma was negative, and an ultrasound of additional chest and mediastinal structures was performed for the chest tenderness.

  13. Ectopic expression of Msx-2 in posterior limb bud mesoderm impairs limb morphogenesis while inducing BMP-4 expression, inhibiting cell proliferation, and promoting apoptosis.

    Science.gov (United States)

    Ferrari, D; Lichtler, A C; Pan, Z Z; Dealy, C N; Upholt, W B; Kosher, R A

    1998-05-01

    expression of BMP-4, a secreted signaling molecule that is coexpressed with Msx-2 during normal limb development in the anterior limb mesoderm, the posterior necrotic zone, and interdigital mesenchyme. This indicates that Msx-2 regulates BMP-4 expression and that the suppressive effects of Msx-2 on limb morphogenesis might be mediated in part by BMP-4. These studies indicate that during normal limb development Msx-2 is a key component of a regulatory network that delimits the boundaries of the progress zone by suppressing the morphogenesis of the regions of the limb mesoderm in which it is highly expressed, thus restricting the outgrowth and formation of skeletal elements and associated structures to the progress zone. We also report that rather large numbers of apoptotic cells as well as proliferating cells are present throughout the AER during all stages of normal limb development we have examined, indicating that many of the cells of the AER are continuously undergoing programmed cell death at the same time that new AER cells are being generated by cell proliferation. Thus, a balance between cell proliferation and programmed cell death may play a very important role in maintaining the activity of the AER. Copyright 1998 Academic Press.

  14. Effects of light quality on flowering and morphogenesis in Hyoscyamus niger L.

    NARCIS (Netherlands)

    Hattab, El A.H.

    1968-01-01

    The present paper is concerned with bolting and morphogenesis of Hyoscyamus niger L. as reactions upon radiation in the visible spectrum.

    Experiments are described in which Hyoscyamus plants were exposed to light of various well defined spectral regions. The light of these

  15. Cardiac septation: a late contribution of the embryonic primary myocardium to heart morphogenesis

    NARCIS (Netherlands)

    Lamers, Wouter H.; Moorman, Antoon F. M.

    2002-01-01

    Heart morphogenesis comprises 2 major consecutive steps, viz. chamber formation followed by septation. Septation is the remodeling of the heart from a single-channel peristaltic pump to a dual-channel, synchronously contracting device with 1-way valves. In the human heart, septation occurs between 4

  16. Growth and morphogenesis of shoot initials of Douglas fir, Pseudotsuga menziesii (Mirb.) Franco, in vitro

    NARCIS (Netherlands)

    Evers, P.W.

    1984-01-01

    An optimalized method of micropropagation of Douglas fir is described. Seasonal changes were found in optima for nitrate and sucrose in the medium and in the optimum for the light intensity during the culture of shoot initials. Differences in morphogenesis were obtained from shoot initials that had

  17. Binding of glutathione to enterovirus capsids is essential for virion morphogenesis.

    NARCIS (Netherlands)

    Thibaut, H.J.; Linden, L. van der; Jiang, P.; Thys, B.; Canela, M.D.; Aguado, L.; Rombaut, B.; Wimmer, E.; Paul, A.; Perez-Perez, M.J.; Kuppeveld, F.J.M. van; Neyts, J.

    2014-01-01

    Enteroviruses (family of the Picornaviridae) cover a large group of medically important human pathogens for which no antiviral treatment is approved. Although these viruses have been extensively studied, some aspects of the viral life cycle, in particular morphogenesis, are yet poorly understood. We

  18. Binding of glutathione to enterovirus capsids is essential for virion morphogenesis

    NARCIS (Netherlands)

    Thibaut, Hendrik Jan; van der Linden, Lonneke; Jiang, Ping; Thys, Bert; Canela, María-Dolores; Aguado, Leire; Rombaut, Bart; Wimmer, Eckard; Paul, Aniko; Pérez-Pérez, María-Jesús; van Kuppeveld, Frank J M; Neyts, Johan

    Enteroviruses (family of the Picornaviridae) cover a large group of medically important human pathogens for which no antiviral treatment is approved. Although these viruses have been extensively studied, some aspects of the viral life cycle, in particular morphogenesis, are yet poorly understood. We

  19. Gastro-oesophageal reflux in large-sized, deep-chested versus small-sized, barrel-chested dogs undergoing spinal surgery in sternal recumbency.

    Science.gov (United States)

    Anagnostou, Tilemahos L; Kazakos, George M; Savvas, Ioannis; Kostakis, Charalampos; Papadopoulou, Paraskevi

    2017-01-01

    The aim of this study was to investigate whether an increased frequency of gastro-oesophageal reflux (GOR) is more common in large-sized, deep-chested dogs undergoing spinal surgery in sternal recumbency than in small-sized, barrelchested dogs. Prospective, cohort study. Nineteen small-sized, barrel-chested dogs (group B) and 26 large-sized, deep-chested dogs (group D). All animals were premedicated with intramuscular (IM) acepromazine (0.05 mg kg -1 ) and pethidine (3 mg kg -1 ) IM. Anaesthesia was induced with intravenous sodium thiopental and maintained with halothane in oxygen. Lower oesophageal pH was monitored continuously after induction of anaesthesia. Gastro-oesophageal reflux was considered to have occurred whenever pH values > 7.5 or < 4 were recorded. If GOR was detected during anaesthesia, measures were taken to avoid aspiration of gastric contents into the lungs and to prevent the development of oesophagitis/oesophageal stricture. The frequency of GOR during anaesthesia was significantly higher in group D (6/26 dogs; 23.07%) than in group B (0/19 dogs; 0%) (p = 0.032). Signs indicative of aspiration pneumonia, oesophagitis or oesophageal stricture were not reported in any of the GOR cases. In large-sized, deep-chested dogs undergoing spinal surgery in sternal recumbency, it would seem prudent to consider measures aimed at preventing GOR and its potentially devastating consequences (oesophagitis/oesophageal stricture, aspiration pneumonia). Copyright © 2016 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

  20. Delayed Sternal Closure in Infant Heart Surgery-The Importance of Where and When: An Analysis of the STS Congenital Heart Surgery Database.

    Science.gov (United States)

    Nelson-McMillan, Kristen; Hornik, Christoph P; He, Xia; Vricella, Luca A; Jacobs, Jeffrey P; Hill, Kevin D; Pasquali, Sara K; Alejo, Diane E; Cameron, Duke E; Jacobs, Marshall L

    2016-11-01

    Delayed sternal closure (DSC) is commonly used to optimize hemodynamic stability after neonatal and infant heart surgery. We hypothesized that duration of sternum left open (SLO) was associated with rate of infection complications, and that location of sternal closure may mitigate infection risk. Infants (age ≤365 days) undergoing index operations with cardiopulmonary bypass and DSC at STS Congenital Heart Surgery Database centers (from 2007 to 2013) with adequate data quality were included. Primary outcome was occurrence of infection complication, defined as one or more of the following: endocarditis, pneumonia, wound infection, wound dehiscence, sepsis, or mediastinitis. Multivariable regression models were fit to assess association of infection complication with: duration of SLO (days), location of DSC procedure (operating room versus elsewhere), and patient and procedural factors. Of 6,127 index operations with SLO at 100 centers, median age and weight were 8 days (IQR, 5-24) and 3.3 kg (IQR, 2.9-3.8); 66% of operations were STAT morbidity category 4 or 5. At least one infection complication occurred in 18.7%, compared with 6.6% among potentially eligible neonates and infants without SLO. Duration of SLO (median, 3 days; IQR, 2-5) was associated with an increased rate of infection complications (p < 0.001). Location of DSC procedure was operating room (16%), intensive care unit (67%), or other (17%). Location of DSC was not associated with rate of infection complications (p = 0.45). Rate of occurrence of infectious complications is high among infants with sternum left open following cardiac surgery. Longer duration of SLO is associated with increased infection complications. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  1. Slug controls stem/progenitor cell growth dynamics during mammary gland morphogenesis.

    Directory of Open Access Journals (Sweden)

    Mayssa Nassour

    Full Text Available Morphogenesis results from the coordination of distinct cell signaling pathways controlling migration, differentiation, apoptosis, and proliferation, along stem/progenitor cell dynamics. To decipher this puzzle, we focused on epithelial-mesenchymal transition (EMT "master genes". EMT has emerged as a unifying concept, involving cell-cell adhesion, migration and apoptotic pathways. EMT also appears to mingle with stemness. However, very little is known on the physiological role and relevance of EMT master-genes. We addressed this question during mammary morphogenesis. Recently, a link between Slug/Snai2 and stemness has been described in mammary epithelial cells, but EMT master genes actual localization, role and targets during mammary gland morphogenesis are not known and we focused on this basic question.Using a Slug-lacZ transgenic model and immunolocalization, we located Slug in a distinct subpopulation covering about 10-20% basal cap and duct cells, mostly cycling cells, coexpressed with basal markers P-cadherin, CK5 and CD49f. During puberty, Slug-deficient mammary epithelium exhibited a delayed development after transplantation, contained less cycling cells, and overexpressed CK8/18, ER, GATA3 and BMI1 genes, linked to luminal lineage. Other EMT master genes were overexpressed, suggesting compensation mechanisms. Gain/loss-of-function in vitro experiments confirmed Slug control of mammary epithelial cell luminal differentiation and proliferation. In addition, they showed that Slug enhances specifically clonal mammosphere emergence and growth, cell motility, and represses apoptosis. Strikingly, Slug-deprived mammary epithelial cells lost their potential to generate secondary clonal mammospheres.We conclude that Slug pathway controls the growth dynamics of a subpopulation of cycling progenitor basal cells during mammary morphogenesis. Overall, our data better define a key mechanism coordinating cell lineage dynamics and morphogenesis, and

  2. Bisbibenzyls, a new type of antifungal agent, inhibit morphogenesis switch and biofilm formation through upregulation of DPP3 in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Li Zhang

    Full Text Available The yeast-to-hypha transition plays a crucial role in the pathogenesis of C. albicans. Farnesol, a quorum sensing molecule (QSM secreted by the fungal itself, could prevent the formation of hyphae and subsequently lead to the defect of biofilm formation. The DPP3, encoding phosphatase, is a key gene in regulating farnesol synthesis. In this study, we screened 24 bisbibenzyls and 2 bibenzyls that were isolated from bryophytes or chemically synthesized by using CLSI method for antifungal effect. Seven bisbibenzyls were found to have antifungal effects with IC(80 less than 32 µg/ml, and among them, plagiochin F, isoriccardin C and BS-34 were found to inhibit the hyphae and biofilm formation of C. albicans in a dose-dependent manner. To uncover the underlying relationship between morphogenesis switch and QSM formation, we measured the farnesol production by HPLC-MS and quantified Dpp3 expression by detecting the fluorescent intensity of green fluorescent protein tagged strain using Confocal Laser Scanning microscopy and Multifunction Microplate Reader. The DPP3 transcripts were determined by real-time PCR. The data indicated that the bisbibenzyls exerted antifungal effects through stimulating the synthesis of farnesol via upregulation of Dpp3, suggesting a potential antifungal application of bisbibenzyls. In addition, our assay provides a novel, visual and convenient method to measure active compounds against morphogenesis switch.

  3. SOX4 regulates gonad morphogenesis and promotes male germ cell differentiation in mice.

    Science.gov (United States)

    Zhao, Liang; Arsenault, Michel; Ng, Ee Ting; Longmuss, Enya; Chau, Tevin Chui-Ying; Hartwig, Sunny; Koopman, Peter

    2017-03-01

    The group C SOX transcription factors SOX4, -11 and -12 play important and mutually overlapping roles in development of a number of organs. Here, we examined the role of SoxC genes during gonadal development in mice. All three genes were expressed in developing gonads of both sexes, predominantly in somatic cells, with Sox4 being most strongly expressed. Sox4 deficiency resulted in elongation of both ovaries and testes, and an increased number of testis cords. While female germ cells entered meiosis normally, male germ cells showed reduced levels of differentiation markers Nanos2 and Dnmt3l and increased levels of pluripotency genes Cripto and Nanog, suggesting that SOX4 may normally act to restrict the pluripotency period of male germ cells and ensure their proper differentiation. Finally, our data reveal that SOX4 (and, to a lesser extent, SOX11 and -12) repressed transcription of the sex-determining gene Sox9 via an upstream testis-specific enhancer core (TESCO) element in fetal gonads, raising the possibility that SOXC proteins may function as transcriptional repressors in a context-dependent manner. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. On the roles and regulation of chondroitin sulfate and heparan sulfate in zebrafish pharyngeal cartilage morphogenesis

    DEFF Research Database (Denmark)

    Holmborn, Katarina; Habicher, Judith; Kasza, Zsolt

    2012-01-01

    The present study addresses the roles of heparan sulfate (HS) proteoglycans and chondroitin sulfate (CS) proteoglycans in the development of zebrafish pharyngeal cartilage structures. uxs1 and b3gat3 mutants, predicted to have impaired biosynthesis of both HS and CS because of defective formation...... levels of CS than control larvae, whereas morpholino-mediated suppression of csgalnact1/csgalnact2 resulted in increased HS biosynthesis. Thus, the balance of the Extl3 and Csgalnact1/Csgalnact2 proteins influences the HS/CS ratio. A characterization of the pharyngeal cartilage element morphologies...

  5. The function and regulation of Tbx22 in avian frontonasal morphogenesis

    Czech Academy of Sciences Publication Activity Database

    Higashihori, N.; Buchtová, Marcela; Richman, J. M.

    2010-01-01

    Roč. 239, - (2010), s. 458-473 ISSN 1058-8388 Institutional research plan: CEZ:AV0Z50450515 Keywords : craniofacial * cleft * BMP Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.864, year: 2010

  6. Date palm (Phoenix dactylifera L.) in vitro morphogenesis in ...

    African Journals Online (AJOL)

    SERVER

    2007-10-18

    Oct 18, 2007 ... In slightly prolonged culture, somatic embryo development was observed from leaf explants in media supplemented with NO3. - and NH4. +. DISCUSSION. This study was aimed at testing the effect of supple- menting basal Eeuwen's medium with growth regulators, sucrose and different nitrogen sources on ...

  7. Transcriptome Sequencing and Differential Gene Expression Analysis of Delayed Gland Morphogenesis in Gossypium australe during Seed Germination

    Science.gov (United States)

    Tao, Tao; Zhao, Liang; Lv, Yuanda; Chen, Jiedan; Hu, Yan; Zhang, Tianzhen; Zhou, Baoliang

    2013-01-01

    The genus Gossypium is a globally important crop that is used to produce textiles, oil and protein. However, gossypol, which is found in cultivated cottonseed, is toxic to humans and non-ruminant animals. Efforts have been made to breed improved cultivated cotton with lower gossypol content. The delayed gland morphogenesis trait possessed by some Australian wild cotton species may enable the widespread, direct usage of cottonseed. However, the mechanisms about the delayed gland morphogenesis are still unknown. Here, we sequenced the first Australian wild cotton species ( Gossypium australe ) and a diploid cotton species ( Gossypium arboreum ) using the Illumina Hiseq 2000 RNA-seq platform to help elucidate the mechanisms underlying gossypol synthesis and gland development. Paired-end Illumina short reads were de novo assembled into 226,184, 213,257 and 275,434 transcripts, clustering into 61,048, 47,908 and 72,985 individual clusters with N50 lengths of 1,710 bp, 1544 BP and 1,743 bp, respectively. The clustered Unigenes were searched against three public protein databases (TrEMBL, SwissProt and RefSeq) and the nucleotide and protein sequences of Gossypium raimondii using BLASTx and BLASTn. A total of 21,987, 17,209 and 25,325 Unigenes were annotated. Of these, 18,766 (85.4%), 14,552 (84.6%) and 21,374 (84.4%) Unigenes could be assigned to GO-term classifications. We identified and analyzed 13,884 differentially expressed Unigenes by clustering and functional enrichment. Terpenoid-related biosynthesis pathways showed differentially regulated expression patterns between the two cotton species. Phylogenetic analysis of the terpene synthases family was also carried out to clarify the classifications of TPSs. RNA-seq data from two distinct cotton species provide comprehensive transcriptome annotation resources and global gene expression profiles during seed germination and gland and gossypol formation. These data may be used to further elucidate various mechanisms and

  8. Microtubule Destabilizer KIF2A Undergoes Distinct Site-Specific Phosphorylation Cascades that Differentially Affect Neuronal Morphogenesis

    Directory of Open Access Journals (Sweden)

    Tadayuki Ogawa

    2015-09-01

    Full Text Available Neurons exhibit dynamic structural changes in response to extracellular stimuli. Microtubules (MTs provide rapid and dramatic cytoskeletal changes within the structural framework. However, the molecular mechanisms and signaling networks underlying MT dynamics remain unknown. Here, we have applied a comprehensive and quantitative phospho-analysis of the MT destabilizer KIF2A to elucidate the regulatory mechanisms of MT dynamics within neurons in response to extracellular signals. Interestingly, we identified two different sets of KIF2A phosphorylation profiles that accelerate (A-type and brake (B-type the MT depolymerization activity of KIF2A. Brain-derived neurotrophic factor (BDNF stimulates PAK1 and CDK5 kinases, which decrease the MT depolymerizing activity of KIF2A through B-type phosphorylation, resulting in enhanced outgrowth of neural processes. In contrast, lysophosphatidic acid (LPA induces ROCK2 kinase, which suppresses neurite outgrowth from round cells via A-type phosphorylation. We propose that these two mutually exclusive forms of KIF2A phosphorylation differentially regulate neuronal morphogenesis during development.

  9. Post-embryonic nerve-associated precursors to adult pigment cells: genetic requirements and dynamics of morphogenesis and differentiation.

    Directory of Open Access Journals (Sweden)

    Erine H Budi

    2011-05-01

    Full Text Available The pigment cells of vertebrates serve a variety of functions and generate a stunning variety of patterns. These cells are also implicated in human pathologies including melanoma. Whereas the events of pigment cell development have been studied extensively in the embryo, much less is known about morphogenesis and differentiation of these cells during post-embryonic stages. Previous studies of zebrafish revealed genetically distinct populations of embryonic and adult melanophores, the ectotherm homologue of amniote melanocytes. Here, we use molecular markers, vital labeling, time-lapse imaging, mutational analyses, and transgenesis to identify peripheral nerves as a niche for precursors to adult melanophores that subsequently migrate to the skin to form the adult pigment pattern. We further identify genetic requirements for establishing, maintaining, and recruiting precursors to the adult melanophore lineage and demonstrate novel compensatory behaviors during pattern regulation in mutant backgrounds. Finally, we show that distinct populations of latent precursors having differential regenerative capabilities persist into the adult. These findings provide a foundation for future studies of post-embryonic pigment cell precursors in development, evolution, and neoplasia.

  10. Histone deacetylase 1 and 2 are essential for murine neural crest proliferation, pharyngeal arch development, and craniofacial morphogenesis.

    Science.gov (United States)

    Milstone, Zachary J; Lawson, Grace; Trivedi, Chinmay M

    2017-12-01

    Craniofacial anomalies involve defective pharyngeal arch development and neural crest function. Copy number variation at 1p35, containing histone deacetylase 1 (Hdac1), or 6q21-22, containing Hdac2, are implicated in patients with craniofacial defects, suggesting an important role in guiding neural crest development. However, the roles of Hdac1 and Hdac2 within neural crest cells remain unknown. The neural crest and its derivatives express both Hdac1 and Hdac2 during early murine development. Ablation of Hdac1 and Hdac2 within murine neural crest progenitor cells cause severe hemorrhage, atrophic pharyngeal arches, defective head morphogenesis, and complete embryonic lethality. Embryos lacking Hdac1 and Hdac2 in the neural crest exhibit decreased proliferation and increased apoptosis in both the neural tube and the first pharyngeal arch. Mechanistically, loss of Hdac1 and Hdac2 upregulates cyclin-dependent kinase inhibitors Cdkn1a, Cdkn1b, Cdkn1c, Cdkn2b, Cdkn2c, and Tp53 within the first pharyngeal arch. Our results show that Hdac1 and Hdac2 function redundantly within the neural crest to regulate proliferation and the development of the pharyngeal arches by means of repression of cyclin-dependent kinase inhibitors. Developmental Dynamics 246:1015-1026, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Semaphorin-Plexin Signaling Controls Mitotic Spindle Orientation during Epithelial Morphogenesis and Repair

    DEFF Research Database (Denmark)

    Xia, Jingjing; Swiercz, Jakub M.; Bañón-Rodríguez, Inmaculada

    2015-01-01

    Morphogenesis, homeostasis, and regeneration of epithelial tissues rely on the accurate orientation of cell divisions, which is specified by the mitotic spindle axis. To remain in the epithelial plane, symmetrically dividing epithelial cells align their mitotic spindle axis with the plane. Here, we...... show that this alignment depends on epithelial cell-cell communication via semaphorin-plexin signaling. During kidney morphogenesis and repair, renal tubular epithelial cells lacking the transmembrane receptor Plexin-B2 or its semaphorin ligands fail to correctly orient the mitotic spindle, leading...... to severe defects in epithelial architecture and function. Analyses of a series of transgenic and knockout mice indicate that Plexin-B2 controls the cell division axis by signaling through its GTPase-activating protein (GAP) domain and Cdc42. Our data uncover semaphorin-plexin signaling as a central...

  12. Reverse engineering the mechanical and molecular pathways in stem cell morphogenesis.

    Science.gov (United States)

    Lu, Kai; Gordon, Richard; Cao, Tong

    2015-03-01

    The formation of relevant biological structures poses a challenge for regenerative medicine. During embryogenesis, embryonic cells differentiate into somatic tissues and undergo morphogenesis to produce three-dimensional organs. Using stem cells, we can recapitulate this process and create biological constructs for therapeutic transplantation. However, imperfect imitation of nature sometimes results in in vitro artifacts that fail to recapitulate the function of native organs. It has been hypothesized that developing cells may self-organize into tissue-specific structures given a correct in vitro environment. This proposition is supported by the generation of neo-organoids from stem cells. We suggest that morphogenesis may be reverse engineered to uncover its interacting mechanical pathway and molecular circuitry. By harnessing the latent architecture of stem cells, novel tissue-engineering strategies may be conceptualized for generating self-organizing transplants. Copyright © 2013 John Wiley & Sons, Ltd.

  13. Essential role for fibrillin-2 in zebrafish notochord and vascular morphogenesis.

    Science.gov (United States)

    Gansner, John M; Madsen, Erik C; Mecham, Robert P; Gitlin, Jonathan D

    2008-10-01

    Recent studies demonstrate that lysyl oxidase cuproenzymes are critical for zebrafish notochord formation, but the molecular mechanisms of copper-dependent notochord morphogenesis are incompletely understood. We, therefore, conducted a forward genetic screen for zebrafish mutants that exhibit notochord sensitivity to lysyl oxidase inhibition, yielding a mutant with defects in notochord and vascular morphogenesis, puff daddygw1 (pfdgw1). Meiotic mapping and cloning reveal that the pfdgw1 phenotype results from disruption of the gene encoding the extracellular matrix protein fibrillin-2, and the spatiotemporal expression of fibrillin-2 is consistent with the pfdgw1 phenotype. Furthermore, each aspect of the pfdgw1 phenotype is recapitulated by morpholino knockdown of fibrillin-2. Taken together, the data reveal a genetic interaction between fibrillin-2 and the lysyl oxidases in notochord formation and demonstrate the importance of fibrillin-2 in specific early developmental processes in zebrafish. Copyright (c) 2008 Wiley-Liss, Inc.

  14. Estrogenic effect of soy isoflavones on mammary gland morphogenesis and gene expression profile

    DEFF Research Database (Denmark)

    Thomsen, Anni R.; Almstrup, Kristian; Nielsen, John E.

    2006-01-01

    We examined the effect of 17 beta-estradiol (E2) and soy isoflavones' exposure on morphogenesis and global gene expression in the murine mammary gland. Three exposure regimens were applied: isoflavones added to the diet throughout either the lactational period (via the dams) or the postweaning...... period and E2 administered orally during the lactational period. Whole mounts of mammary glands were evaluated both in juvenile and adult animals with respect to branching morphogenesis and terminal end bud (TEB) formation. At postnatal day (PND) 28, we observed a significant increase in branching...... isoflavone and E2 exposure was further substantiated by changes in gene expression, since the same groups of genes were up- and downregulated, particularly in the E2 and postweaning isoflavone regimen. All changes in gene expression correlated with changes in the cellular composition of the gland, i.e., more...

  15. Signaling pathways regulating murine pancreatic development

    DEFF Research Database (Denmark)

    Serup, Palle

    2012-01-01

    The recent decades have seen a huge expansion in our knowledge about pancreatic development. Numerous lineage-restricted transcription factor genes have been identified and much has been learned about their function. Similarly, numerous signaling pathways important for pancreas development have...... been identified and the specific roles have been investigated by genetic and cell biological methods. The present review presents an overview of the principal signaling pathways involved in regulating murine pancreatic growth, morphogenesis, and cell differentiation....

  16. Septins from the phytopathogenic fungus Ustilago maydis are required for proper morphogenesis but dispensable for virulence.

    Directory of Open Access Journals (Sweden)

    Isabel Alvarez-Tabarés

    Full Text Available BACKGROUND: Septins are a highly conserved family of GTP-binding proteins involved in multiple cellular functions, including cell division and morphogenesis. Studies of septins in fungal cells underpin a clear correlation between septin-based structures and fungal morphology, providing clues to understand the molecular frame behind the varied morphologies found in fungal world. METHODOLOGY/PRINCIPAL FINDINGS: Ustilago maydis genome has the ability to encode four septins. Here, using loss-of-function as well as GFP-tagged alleles of these septin genes, we investigated the roles of septins in the morphogenesis of this basidiomycete fungus. We described that septins in U. maydis could assemble into at least three different structures coexisting in the same cell: bud neck collars, band-like structures at the growing tip, and long septin fibers that run from pole to pole near the cell cortex. We also found that in the absence of septins, U. maydis cells lost their elongated shape, became wider at the central region and ended up losing their polarity, pointing to an important role of septins in the morphogenesis of this fungus. These morphological defects were alleviated in the presence of an osmotic stabilizer suggesting that absence of septins affected the proper formation of the cell wall, which was coherent with a higher sensitivity of septin defective cells to drugs that affect cell wall construction as well as exocytosis. As U. maydis is a phytopathogen, we analyzed the role of septins in virulence and found that in spite of the described morphological defects, septin mutants were virulent in corn plants. CONCLUSIONS/SIGNIFICANCE: Our results indicated a major role of septins in morphogenesis in U. maydis. However, in contrast to studies in other fungal pathogens, in which septins were reported to be necessary during the infection process, we found a minor role of septins during corn infection by U. maydis.

  17. Binding of glutathione to enterovirus capsids is essential for virion morphogenesis.

    Directory of Open Access Journals (Sweden)

    Hendrik Jan Thibaut

    2014-04-01

    Full Text Available Enteroviruses (family of the Picornaviridae cover a large group of medically important human pathogens for which no antiviral treatment is approved. Although these viruses have been extensively studied, some aspects of the viral life cycle, in particular morphogenesis, are yet poorly understood. We report the discovery of TP219 as a novel inhibitor of the replication of several enteroviruses, including coxsackievirus and poliovirus. We show that TP219 binds directly glutathione (GSH, thereby rapidly depleting intracellular GSH levels and that this interferes with virus morphogenesis without affecting viral RNA replication. The inhibitory effect on assembly was shown not to depend on an altered reducing environment. Using TP219, we show that GSH is an essential stabilizing cofactor during the transition of protomeric particles into pentameric particles. Sequential passaging of coxsackievirus B3 in the presence of low GSH-levels selected for GSH-independent mutants that harbored a surface-exposed methionine in VP1 at the interface between two protomers. In line with this observation, enteroviruses that already contained this surface-exposed methionine, such as EV71, did not rely on GSH for virus morphogenesis. Biochemical and microscopical analysis provided strong evidence for a direct interaction between GSH and wildtype VP1 and a role for this interaction in localizing assembly intermediates to replication sites. Consistently, the interaction between GSH and mutant VP1 was abolished resulting in a relocalization of the assembly intermediates to replication sites independent from GSH. This study thus reveals GSH as a novel stabilizing host factor essential for the production of infectious enterovirus progeny and provides new insights into the poorly understood process of morphogenesis.

  18. Proliferation and apoptosis in early molar morphogenesis - voles as models in odontogenesis

    Czech Academy of Sciences Publication Activity Database

    Šetková, Jana; Lesot, H.; Matalová, Eva; Witter, K.; Matulová, Petra; Míšek, Ivan

    2006-01-01

    Roč. 50, 5 (2006), s. 481-489 ISSN 0214-6282 R&D Projects: GA ČR GA304/04/0101; GA MŠk OC B23.001 Grant - others:COST STSM B23-00981 Institutional research plan: CEZ:AV0Z50450515 Keywords : tooth development * morphogenesis * Microtus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.577, year: 2006

  19. Review of aragonite and calcite crystal morphogenesis in thermal spring systems

    Science.gov (United States)

    Jones, Brian

    2017-06-01

    Aragonite and calcite crystals are the fundamental building blocks of calcareous thermal spring deposits. The diverse array of crystal morphologies found in these deposits, which includes monocrystals, mesocrystals, skeletal crystals, dendrites, and spherulites, are commonly precipitated under far-from-equilibrium conditions. Such crystals form through both abiotic and biotic processes. Many crystals develop through non-classical crystal growth models that involve the arrangement of nanocrystals in a precisely controlled crystallographic register. Calcite crystal morphogenesis has commonly been linked to a ;driving force;, which is a conceptual measure of the distance of the growth conditions from equilibrium conditions. Essentially, this scheme indicates that increasing levels of supersaturation and various other parameters that produce a progressive change from monocrystals and mesocrystals to skeletal crystals to crystallographic and non-crystallographic dendrites, to dumbbells, to spherulites. Despite the vast amount of information available from laboratory experiments and natural spring systems, the precise factors that control the driving force are open to debate. The fact that calcite crystal morphogenesis is still poorly understood is largely a reflection of the complexity of the factors that influence aragonite and calcite precipitation. Available information indicates that variations in calcite crystal morphogenesis can be attributed to physical and chemical parameters of the parent water, the presence of impurities, the addition of organic or inorganic additives to the water, the rate of crystal growth, and/or the presence of microbes and their associated biofilms. The problems in trying to relate crystal morphogenesis to specific environmental parameters arise because it is generally impossible to disentangle the controlling factor(s) from the vast array of potential parameters that may act alone or in unison with each other.

  20. Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo.

    Science.gov (United States)

    Barriga, Elias H; Franze, Kristian; Charras, Guillaume; Mayor, Roberto

    2018-02-22

    Collective cell migration is essential for morphogenesis, tissue remodelling and cancer invasion. In vivo, groups of cells move in an orchestrated way through tissues. This movement involves mechanical as well as molecular interactions between cells and their environment. While the role of molecular signals in collective cell migration is comparatively well understood, how tissue mechanics influence collective cell migration in vivo remains unknown. Here we investigated the importance of mechanical cues in the collective migration of the Xenopus laevis neural crest cells, an embryonic cell population whose migratory behaviour has been likened to cancer invasion. We found that, during morphogenesis, the head mesoderm underlying the cephalic neural crest stiffens. This stiffening initiates an epithelial-to-mesenchymal transition in neural crest cells and triggers their collective migration. To detect changes in their mechanical environment, neural crest cells use mechanosensation mediated by the integrin-vinculin-talin complex. By performing mechanical and molecular manipulations, we show that mesoderm stiffening is necessary and sufficient to trigger neural crest migration. Finally, we demonstrate that convergent extension of the mesoderm, which starts during gastrulation, leads to increased mesoderm stiffness by increasing the cell density underneath the neural crest. These results show that convergent extension of the mesoderm has a role as a mechanical coordinator of morphogenesis, and reveal a link between two apparently unconnected processes-gastrulation and neural crest migration-via changes in tissue mechanics. Overall, we demonstrate that changes in substrate stiffness can trigger collective cell migration by promoting epithelial-to-mesenchymal transition in vivo. More broadly, our results raise the idea that tissue mechanics combines with molecular effectors to coordinate morphogenesis.

  1. Topological laser speckle analyzer of differentiation and proliferation activity during morphogenesis in cell cultures

    OpenAIRE

    Notchenko A.V.; Gradov O.V.

    2011-01-01

    An automated system for morpho-topological determination of cell division phases and structur al differentiation of tissues during morphogenesis was implemented on the basis of topological properties of cell cultures, considered within the framework of set and manifold theories. A simple robotic hardware and software system based on Zeiss microscope with a modified stage and a Velleman manipulator KSR-1 allow to control the laser module position, carrying out the angular irradiation of s...

  2. Binding of Glutathione to Enterovirus Capsids Is Essential for Virion Morphogenesis

    Science.gov (United States)

    Thibaut, Hendrik Jan; Thys, Bert; Canela, María-Dolores; Aguado, Leire; Wimmer, Eckard; Paul, Aniko; Pérez-Pérez, María-Jesús; van Kuppeveld, Frank J. M.; Neyts, Johan

    2014-01-01

    Enteroviruses (family of the Picornaviridae) cover a large group of medically important human pathogens for which no antiviral treatment is approved. Although these viruses have been extensively studied, some aspects of the viral life cycle, in particular morphogenesis, are yet poorly understood. We report the discovery of TP219 as a novel inhibitor of the replication of several enteroviruses, including coxsackievirus and poliovirus. We show that TP219 binds directly glutathione (GSH), thereby rapidly depleting intracellular GSH levels and that this interferes with virus morphogenesis without affecting viral RNA replication. The inhibitory effect on assembly was shown not to depend on an altered reducing environment. Using TP219, we show that GSH is an essential stabilizing cofactor during the transition of protomeric particles into pentameric particles. Sequential passaging of coxsackievirus B3 in the presence of low GSH-levels selected for GSH-independent mutants that harbored a surface-exposed methionine in VP1 at the interface between two protomers. In line with this observation, enteroviruses that already contained this surface-exposed methionine, such as EV71, did not rely on GSH for virus morphogenesis. Biochemical and microscopical analysis provided strong evidence for a direct interaction between GSH and wildtype VP1 and a role for this interaction in localizing assembly intermediates to replication sites. Consistently, the interaction between GSH and mutant VP1 was abolished resulting in a relocalization of the assembly intermediates to replication sites independent from GSH. This study thus reveals GSH as a novel stabilizing host factor essential for the production of infectious enterovirus progeny and provides new insights into the poorly understood process of morphogenesis. PMID:24722756

  3. Gibberellin influence on the morphogenesis of the moss Bryum argenteum Hedw. in in vitro conditions

    OpenAIRE

    Sabovljević Aneta; Sabovljević Marko; Grubišić D.

    2010-01-01

    The moss Bryum argenteum Hedw. was treated with gibberellins as well as some inhibitors of gibberellin biosynthesis in order to investigate their influence on B. argenteum morphogenesis. Generally, gibberellins have not been chemically identified in bryophytes, while other groups of classical phytohormones (auxins, cytokinins, abscisic acid and ethylene) have been chemically identified in these plants. The in vitro culture of the moss Bryum argenteum was established from sterilized spores. Th...

  4. The von Hippel-Lindau tumor suppressor gene inhibits hepatocyte growth factor/scatter factor-induced invasion and branching morphogenesis in renal carcinoma cells.

    Science.gov (United States)

    Koochekpour, S; Jeffers, M; Wang, P H; Gong, C; Taylor, G A; Roessler, L M; Stearman, R; Vasselli, J R; Stetler-Stevenson, W G; Kaelin, W G; Linehan, W M; Klausner, R D; Gnarra, J R; Vande Woude, G F

    1999-09-01

    Loss of function in the von Hippel-Lindau (VHL) tumor suppressor gene occurs in familial and most sporadic renal cell carcinomas (RCCs). VHL has been linked to the regulation of cell cycle cessation (G(0)) and to control of expression of various mRNAs such as for vascular endothelial growth factor. RCC cells express the Met receptor tyrosine kinase, and Met mediates invasion and branching morphogenesis in many cell types in response to hepatocyte growth factor/scatter factor (HGF/SF). We examined the HGF/SF responsiveness of RCC cells containing endogenous mutated (mut) forms of the VHL protein (VHL-negative RCC) with that of isogenic cells expressing exogenous wild-type (wt) VHL (VHL-positive RCC). We found that VHL-negative 786-0 and UOK-101 RCC cells were highly invasive through growth factor-reduced (GFR) Matrigel-coated filters and exhibited an extensive branching morphogenesis phenotype in response to HGF/SF in the three-dimensional (3D) GFR Matrigel cultures. In contrast, the phenotypes of A498 VHL-negative RCC cells were weaker, and isogenic RCC cells ectopically expressing wt VHL did not respond at all. We found that all VHL-negative RCC cells expressed reduced levels of tissue inhibitor of metalloproteinase 2 (TIMP-2) relative to the wt VHL-positive cells, implicating VHL in the regulation of this molecule. However, consistent with the more invasive phenotype of the 786-0 and UOK-101 VHL-negative RCC cells, the levels of TIMP-1 and TIMP-2 were reduced and levels of the matrix metalloproteinases 2 and 9 were elevated compared to the noninvasive VHL-positive RCC cells. Moreover, recombinant TIMPs completely blocked HGF/SF-mediated branching morphogenesis, while neutralizing antibodies to the TIMPs stimulated HGF/SF-mediated invasion in vitro. Thus, the loss of the VHL tumor suppressor gene is central to changes that control tissue invasiveness, and a more invasive phenotype requires additional genetic changes seen in some but not all RCC lines. These

  5. [Analysis of surgical treatment with pectoralis major muscle flap for deep sternal infection after cardiac surgery: a case series of 189 patients].

    Science.gov (United States)

    Liu, Dong; Wang, Wenzhang; Cai, Aibing; Han, Zhiyi; Li, Xiyuan; Ma, Jiagui

    2015-03-01

    To analyze and summarize the clinical features and experience in surgical treatment of deep sternal infection (DSWI). This was a retrospective study. From January 2008 to December 2013, 189 patients with secondary DSWI after cardiac surgery underwent the pectoralis major muscle flap transposition in our department. There were 116 male and 73 female patients. The mean age was (54 ± 21) years, the body mass index was (26. 1 ± 1. 3) kg/m2. The incidence of postoperation DSWI were after isolated coronary artery bypass grafting (CABG) in 93 patients, after other heart surgery plus CABG in 13 patients, after valve surgery in 47 patients, after thoracic aortic surgery in 16 patients, after congenital heart disease in 18 patients, and after cardiac injury in 2 patients. Clean patients' wound and extract secretions, clear the infection thoroughly by surgery and select antibiotics based on susceptibility results, and then repair the wound with appropriate muscle flap, place drain tube with negative pressure. Of all the 189 patients, 184 used isolate pectoralis, 1 used isolate rectus, and 4 used pectoralis plus rectus. The operative wounds of 179 patients were primary healing (94. 7%). Hospital discharge was postponed by 1 week for 7 patients, due to subcutaneous wound infection. Subcutaneous wound infection occurred again in 8 patients 1 week after hospital discharge, and their wounds healed after wound dressing. Nine patients (4. 7%) did not recover, due to residue of the sequestrum and costal chondritis, whom were later cured by undergoing a second treatment of debridement and pectoralis major muscle flap transposition. Eight patients died, in which 2 died of respiratory failure, 2 died of bacterial endocarditis with septicemia, 2 died of renal failure, 1 died of intraoperative bleeding leading to brain death and the 1 died of heart failure. The mortality rate was 4. 2% . The average length of postoperative hospital stay was (14 ± 5) days. The longest postoperative

  6. The ERM protein Moesin is essential for neuronal morphogenesis and long-term memory in Drosophila.

    Science.gov (United States)

    Freymuth, Patrick S; Fitzsimons, Helen L

    2017-08-29

    Moesin is a cytoskeletal adaptor protein that plays an important role in modification of the actin cytoskeleton. Rearrangement of the actin cytoskeleton drives both neuronal morphogenesis and the structural changes in neurons that are required for long-term memory formation. Moesin has been identified as a candidate memory gene in Drosophila, however, whether it is required for memory formation has not been evaluated. Here, we investigate the role of Moesin in neuronal morphogenesis and in short- and long-term memory formation in the courtship suppression assay, a model of associative memory. We found that both knockdown and overexpression of Moesin led to defects in axon growth and guidance as well as dendritic arborization. Moreover, reduction of Moesin expression or expression of a constitutively active phosphomimetic in the adult Drosophila brain had no effect on short term memory, but prevented long-term memory formation, an effect that was independent of its role in development. These results indicate a critical role for Moesin in both neuronal morphogenesis and long-term memory formation.

  7. Quantification of local matrix deformations and mechanical properties during capillary morphogenesis in 3D.

    Science.gov (United States)

    Kniazeva, Ekaterina; Weidling, John W; Singh, Rahul; Botvinick, Elliot L; Digman, Michelle A; Gratton, Enrico; Putnam, Andrew J

    2012-04-01

    Reciprocal mechanical interactions between cells and the extracellular matrix (ECM) are thought to play important instructive roles in branching morphogenesis. However, most studies to date have failed to characterize these interactions on a length scale relevant to cells, especially in three-dimensional (3D) matrices. Here we utilized two complementary methods, spatio-temporal image correlation spectroscopy (STICS) and laser optical tweezers-based active microrheology (AMR), to quantify endothelial cell (EC)-mediated deformations of individual ECM elements and the local ECM mechanical properties, respectively, during the process of capillary morphogenesis in a 3D cell culture model. In experiments in which the ECM density was systematically varied, STICS revealed that the rate at which ECs deformed individual ECM fibers on the microscale positively correlated with capillary sprouting on the macroscale. ECs expressing constitutively active V14-RhoA displaced individual matrix fibers at significantly faster rates and displayed enhanced capillary sprouting relative to wild-type cells, while those expressing dominant-negative N19-RhoA behaved in an opposite fashion. In parallel, AMR revealed a local stiffening of the ECM proximal to the tips of sprouting ECs. By quantifying the dynamic physical properties of the cell-ECM interface in both space and time, we identified a correlation linking ECM deformation rates and local ECM stiffening at the microscale with capillary morphogenesis at the macroscale. This journal is © The Royal Society of Chemistry 2012

  8. Quantification of local matrix deformations and mechanical properties during capillary morphogenesis in 3D†‡

    Science.gov (United States)

    Kniazeva, Ekaterina; Weidling, John W.; Singh, Rahul; Botvinick, Elliot L.; Digman, Michelle A.; Gratton, Enrico

    2013-01-01

    Reciprocal mechanical interactions between cells and the extracellular matrix (ECM) are thought to play important instructive roles in branching morphogenesis. However, most studies to date have failed to characterize these interactions on a length scale relevant to cells, especially in three-dimensional (3D) matrices. Here we utilized two complementary methods, spatio-temporal image correlation spectroscopy (STICS) and laser optical tweezers-based active microrheology (AMR), to quantify endothelial cell (EC)-mediated deformations of individual ECM elements and the local ECM mechanical properties, respectively, during the process of capillary morphogenesis in a 3D cell culture model. In experiments in which the ECM density was systematically varied, STICS revealed that the rate at which ECs deformed individual ECM fibers on the microscale positively correlated with capillary sprouting on the macroscale. ECs expressing constitutively active V14-RhoA displaced individual matrix fibers at significantly faster rates and displayed enhanced capillary sprouting relative to wild-type cells, while those expressing dominant-negative N19-RhoA behaved in an opposite fashion. In parallel, AMR revealed a local stiffening of the ECM proximal to the tips of sprouting ECs. By quantifying the dynamic physical properties of the cell-ECM interface in both space and time, we identified a correlation linking ECM deformation rates and local ECM stiffening at the microscale with capillary morphogenesis at the macroscale. PMID:22281872

  9. Epimorphin mediates mammary luminal morphogenesis through control of C/EBPbeta

    International Nuclear Information System (INIS)

    Hirai, Yohei; Radisky, Derek; Boudreau, Rosanne; Simian, Marina; Stevens, Mary E.; Oka, Yumiko; Takebe, Kyoko; Niwa, Shinichiro; Bissell, Mina J.

    2002-01-01

    We have previously shown that epimorphin, a protein expressed on the surface of myoepithelial and fibroblast cells of the mammary gland, acts as a multifunctional morphogen of mammary epithelial cells. Here, we present the molecular mechanism by which epimorphin mediates luminal morphogenesis. Treatment of cells with epimorphin to induce lumen formation greatly increases the overall expression of transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) and alters the relative expression of its two principal isoforms, LIP and LAP. These alterations were shown to be essential for the morphogenetic activities, as constitutive expression of LIP was sufficient to produce lumen formation, while constitutive expression of LAP blocked epimorphin-mediated luminal morphogenesis. Furthermore, in a transgenic mouse model in which epimorphin expression was expressed in an apolar fashion on the surface of mammary epithelial cells, we found increased expression of C/EBPbeta, increased relative expression of LIP to LAP, and enlarged ductal lumina. Together, our studies demonstrate a role for epimorphin in luminal morphogenesis through control of C/EBPbeta expression

  10. Morphogenesis of Pestiviruses: New Insights from Ultrastructural Studies of Strain Giraffe-1

    Science.gov (United States)

    Mast, Jan; Thiel, Heinz-Jürgen; König, Matthias

    2014-01-01

    Knowledge on the morphogenesis of pestiviruses is limited due to low virus production in infected cells. In order to localize virion morphogenesis and replication sites of pestiviruses and to examine intracellular virion transport, a cell culture model was established to facilitate ultrastructural studies. Based on results of virus growth kinetic analysis and quantification of viral RNA, pestivirus strain Giraffe-1 turned out to be a suitable candidate for studies on virion generation and export from culture cells. Using conventional transmission electron microscopy and single-tilt electron tomography, we found virions located predominately in the lumen of the endoplasmic reticulum (ER) in infected cells and were able to depict the budding process of virions at ER membranes. Colocalization of the viral core protein and the envelope glycoprotein E2 with the ER marker protein disulfide isomerase (PDI) was demonstrated by immunogold labeling of cryosections. Moreover, pestivirions could be shown in transport vesicles and the Golgi complex and during exocytosis. Interestingly, viral capsid protein and double-stranded RNA (dsRNA) were detected in multivesicular bodies (MVBs), which implies that the endosomal compartment plays a role in pestiviral replication. Significant cellular membrane alterations such as those described for members of the Flavivirus and Hepacivirus genera were not found. Based on the gained morphological data, we present a consistent model of pestivirus morphogenesis. PMID:24352462

  11. ETS transcription factor ELF5 induces lumen formation in a 3D model of mammary morphogenesis and its expression is inhibited by Jak2 inhibitor TG101348.

    Science.gov (United States)

    Chean, Jennifer; Chen, Charng-Jui; Shively, John E

    2017-10-01

    The loss of expression of a single gene can revert normal tissue to a malignant phenotype. For example, while normal breast has high lumenal expression of CEACAM1, the majority of breast cancers exhibit the early loss of this gene with the concurrent loss of their lumenal phenotype. MCF7 cells that lack CEACAM1 expression and fail to form lumena in 3D culture, regain the normal phenotype when transfected with CEACAM1. In order to probe the mechanism of this gain of function, we treated these cells with the clinically relevant Jak2 inhibitor TG101348 (TG), expecting that disruption of the prolactin receptor signaling pathway would interfere with the positive effects of transfection of MCF7 cells with CEACAM1. Indeed, lumen formation was inhibited, resulting in the down regulation of a set of genes, likely involved in the complex process of lumen formation. As expected, inhibition of the expression of many of these genes also inhibited lumen formation, confirming their involvement in a single pathway. Among the genes identified by the inhibition assay, ETS transcription factor ELF5 stood out, since it has been identified as a master regulator of mammary morphogenesis, and is associated with prolactin receptor signaling. When ELF5 was transfected into the parental MCF7 cells that lack CEACAM1, lumen formation was restored, indicating that ELF5 can replace CEACAM1 in this model system of lumenogenesis. We conclude that the event(s) that led to the loss of expression of CEACAM1 is epistatic in that multiple genes associated with a critical pathway were affected, but that restoration of the normal phenotype can be achieved with reactivation of certain genes at various nodal points in tissue morphogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. TRAF4, at the Crossroad between Morphogenesis and Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rousseau, Adrien; Rio, Marie-Christine; Alpy, Fabien, E-mail: Fabien.Alpy@igbmc.fr [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), UMR 7104 CNRS, U964 INSERM, Université de Strasbourg, BP 10142, 67404 Illkirch, C.U. de Strasbourg (France)

    2011-06-21

    Tumor Necrosis Factor Receptor-Associated Factor 4 (TRAF4) is a gene whose expression is altered in cancers. It is overexpressed in a variety of carcinomas of different origins, often as a consequence of amplification. TRAF4 encodes an adaptor protein that belongs to the TRAF protein family. While most TRAF proteins influence immune and inflammation processes, TRAF4 is mainly involved in developmental and morphogenic processes. Interestingly, this protein has been shown to be linked to crucial cellular functions such as cell polarity and the regulation of reactive oxygen species production.

  13. Profilin is required for viral morphogenesis, syncytium formation, and cell-specific stress fiber induction by respiratory syncytial virus

    Directory of Open Access Journals (Sweden)

    Barik Sailen

    2003-05-01

    Full Text Available Abstract Background Actin is required for the gene expression and morphogenesis of respiratory syncytial virus (RSV, a clinically important Pneumovirus of the Paramyxoviridae family. In HEp-2 cells, RSV infection also induces actin stress fibers, which may be important in the immunopathology of the RSV disease. Profilin, a major regulator of actin polymerization, stimulates viral transcription in vitro. Thus, we tested the role of profilin in RSV growth and RSV-actin interactions in cultured cells (ex vivo. Results We tested three cell lines: HEp-2 (human, A549 (human, and L2 (rat. In all three, RSV grew well and produced fused cells (syncytium, and two RSV proteins, namely, the phosphoprotein P and the nucleocapsid protein N, associated with profilin. In contrast, induction of actin stress fibers by RSV occurred in HEp-2 and L2 cells, but not in A549. Knockdown of profilin by RNA interference had a small effect on viral macromolecule synthesis but strongly inhibited maturation of progeny virions, cell fusion, and induction of stress fibers. Conclusions Profilin plays a cardinal role in RSV-mediated cell fusion and viral maturation. In contrast, interaction of profilin with the viral transcriptional proteins P and N may only nominally activate viral RNA-dependent RNA polymerase. Stress fiber formation is a cell-specific response to infection, requiring profilin and perhaps other signaling molecules that are absent in certain cell lines. Stress fibers per se play no role in RSV replication in cell culture. Clearly, the cellular architecture controls multiple steps of host-RSV interaction, some of which are regulated by profilin.

  14. Org-1 is required for the diversification of circular visceral muscle founder cells and normal midgut morphogenesis.

    Science.gov (United States)

    Schaub, Christoph; Frasch, Manfred

    2013-04-15

    The T-Box family of transcription factors plays fundamental roles in the generation of appropriate spatial and temporal gene expression profiles during cellular differentiation and organogenesis in animals. In this study we report that the Drosophila Tbx1 orthologue optomotor-blind-related-gene-1 (org-1) exerts a pivotal function in the diversification of circular visceral muscle founder cell identities in Drosophila. In embryos mutant for org-1, the specification of the midgut musculature per se is not affected, but the differentiating midgut fails to form the anterior and central midgut constrictions and lacks the gastric caeca. We demonstrate that this phenotype results from the nearly complete loss of the founder cell specific expression domains of several genes known to regulate midgut morphogenesis, including odd-paired (opa), teashirt (tsh), Ultrabithorax (Ubx), decapentaplegic (dpp) and wingless (wg). To address the mechanisms that mediate the regulatory inputs from org-1 towards Ubx, dpp, and wg in these founder cells we genetically dissected known visceral mesoderm specific cis-regulatory-modules (CRMs) of these genes. The analyses revealed that the activities of the dpp and wg CRMs depend on org-1, the CRMs are bound by Org-1 in vivo and their T-Box binding sites are essential for their activation in the visceral muscle founder cells. We conclude that Org-1 acts within a well-defined signaling and transcriptional network of the trunk visceral mesoderm as a crucial founder cell-specific competence factor, in concert with the general visceral mesodermal factor Biniou. As such, it directly regulates several key genes involved in the establishment of morphogenetic centers along the anteroposterior axis of the visceral mesoderm, which subsequently organize the formation of midgut constrictions and gastric caeca and thereby determine the morphology of the midgut. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Arabidopsis homolog of trithorax1 (ATX1) is required for cell production, patterning, and morphogenesis in root development.

    Science.gov (United States)

    Napsucialy-Mendivil, Selene; Alvarez-Venegas, Raúl; Shishkova, Svetlana; Dubrovsky, Joseph G

    2014-12-01

    Arabidopsis homolog of trithorax1 (ATX1/SDG27), a known regulator of flower development, encodes a H3K4histone methyltransferase that maintains a number of genes in an active state. In this study, the role of ATX1 in root development was evaluated. The loss-of-function mutant atx1-1 was impaired in primary root growth. The data suggest that ATX1 controls root growth by regulating cell cycle duration, cell production, and the transition from cell proliferation in the root apical meristem (RAM) to cell elongation. In atx1-1, the quiescent centre (QC) cells were irregular in shape and more expanded than those of the wild type. This feature, together with the atypical distribution of T-divisions, the presence of oblique divisions, and the abnormal cell patterning in the RAM, suggests a lack of coordination between cell division and cell growth in the mutant. The expression domain of QC-specific markers was expanded both in the primary RAM and in the developing lateral root primordia of atx1-1 plants. These abnormalities were independent of auxin-response gradients. ATX1 was also found to be required for lateral root initiation, morphogenesis, and emergence. The time from lateral root initiation to emergence was significantly extended in the atx1-1 mutant. Overall, these data suggest that ATX1 is involved in the timing of root development, stem cell niche maintenance, and cell patterning during primary and lateral root development. Thus, ATX1 emerges as an important player in root system architecture. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  16. Trim9 Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory.

    Science.gov (United States)

    Winkle, Cortney C; Olsen, Reid H J; Kim, Hyojin; Moy, Sheryl S; Song, Juan; Gupton, Stephanie L

    2016-05-04

    During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9(-/-) adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9(-/-) mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors. Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of Trim9 elevated dendritic arborization of hippocampal neurons in vitro and in vivo Adult-born dentate granule cells lacking Trim9 similarly exhibited excessive dendritic arborization and mislocalization of cell bodies in vivo These cellular defects were associated with severe deficits in spatial learning and memory. Copyright © 2016 the authors 0270-6474/16/364940-19$15.00/0.

  17. Role of Arf GTPases in fungal morphogenesis and virulence.

    Directory of Open Access Journals (Sweden)

    Hayet Labbaoui

    2017-02-01

    Full Text Available Virulence of the human fungal pathogen Candida albicans depends on the switch from budding to filamentous growth, which requires sustained membrane traffic and polarized growth. In many organisms, small GTPases of the Arf (ADP-ribosylation factor family regulate membrane/protein trafficking, yet little is known about their role in fungal filamentous growth. To investigate these GTPases in C. albicans, we generated loss of function mutants in all 3 Arf proteins, Arf1-Arf3, and 2 Arf-like proteins, Arl1 and Arl3. Our results indicate that of these proteins, Arf2 is required for viability and sensitivity to antifungal drugs. Repressible ARF2 expression results in defects in filamentous growth, cell wall integrity and virulence, likely due to alteration of the Golgi. Arl1 is also required for invasive filamentous growth and, although arl1/arl1 cells can initiate hyphal growth, hyphae are substantially shorter than that of the wild-type, due to the inability of this mutant to maintain hyphal growth at a single site. We show that this defect does not result from an alteration of phospholipid distribution and is unlikely to result from the sole Golgin Imh1 mislocalization, as Imh1 is not required for invasive filamentous growth. Rather, our results suggest that the arl1/arl1 hyphal growth defect results from increased secretion in this mutant. Strikingly, the arl1/arl1 mutant is drastically reduced in virulence during oropharyngeal candidiasis. Together, our results highlight the importance of Arl1 and Arf2 as key regulators of hyphal growth and virulence in C. albicans and identify a unique function of Arl1 in secretion.

  18. High plasticity in epithelial morphogenesis during insect dorsal closure

    Directory of Open Access Journals (Sweden)

    Kristen A. Panfilio

    2013-09-01

    Insect embryos complete the outer form of the body via dorsal closure (DC of the epidermal flanks, replacing the transient extraembryonic (EE tissue. Cell shape changes and morphogenetic behavior are well characterized for DC in Drosophila, but these data represent a single species with a secondarily reduced EE component (the amnioserosa that is not representative across the insects. Here, we examine DC in the red flour beetle, Tribolium castaneum, providing the first detailed, functional analysis of DC in an insect with complete EE tissues (distinct amnion and serosa. Surprisingly, we find that differences between Drosophila and Tribolium DC are not restricted to the EE tissue, but also encompass the dorsal epidermis, which differs in cellular architecture and method of final closure (zippering. We then experimentally manipulated EE tissue complement via RNAi for Tc-zen1, allowing us to eliminate the serosa and still examine viable DC in a system with a single EE tissue (the amnion. We find that the EE domain is particularly plastic in morphogenetic behavior and tissue structure. In contrast, embryonic features and overall kinetics are robust to Tc-zen1RNAi manipulation in Tribolium and conserved with a more distantly related insect, but remain substantially different from Drosophila. Although correct DC is essential, plasticity and regulative, compensatory capacity have permitted DC to evolve within the insects. Thus, DC does not represent a strong developmental constraint on the nature of EE development, a property that may have contributed to the reduction of the EE component in the fly lineage.

  19. MiR-181a-5p is downregulated in hepatocellular carcinoma and suppresses motility, invasion and branching-morphogenesis by directly targeting c-Met.

    Science.gov (United States)

    Korhan, Peyda; Erdal, Esra; Atabey, Neşe

    2014-08-08

    c-Met receptor tyrosine kinase has been regarded as a promising therapeutic target for hepatocellular carcinoma (HCC). Recently, microRNAs (miRNAs) have been shown as a novel mechanism to control c-Met expression in cancer. In this study, we investigate the potential contribution of miR-181a-5p dysregulation to the biology of c-Met overexpression in HCC. Herein, we found an inverse expression pattern between miR-181a-5p and c-Met expression in normal, cirrhotic and HCC liver tissues. Luciferase assay confirmed that miR-181a-5p binding to the 3'-UTR of c-Met downregulated the expression of c-Met in HCC cells. Overexpression of miR-181a-5p suppressed both HGF-independent and -dependent activation of c-Met and consequently diminished branching-morphogenesis and invasion. Combined treatment with miR-181a-5p and c-Met inhibitor led to a further inhibition of c-Met-driven cellular activities. Knockdown of miR-181a-5p promoted HGF-independent/-dependent signaling of c-Met and accelerated migration, invasion and branching-morphogenesis. In conclusion, our results demonstrated for the first time that c-Met is a functional target gene of miR-181a-5p and the loss of miR-181a-5p expression led to the activation of c-Met-mediated oncogenic signaling in hepatocarcinogenesis. These findings display a novel molecular mechanism of c-Met regulation in HCC and strategies to increase miR-181a5p level might be an alternative approach for the enhancement of the inhibitory effects of c-Met inhibitors. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Cellular growth in plants requires regulation of cell wall biochemistry.

    Science.gov (United States)

    Chebli, Youssef; Geitmann, Anja

    2017-02-01

    Cell and organ morphogenesis in plants are regulated by the chemical structure and mechanical properties of the extracellular matrix, the cell wall. The two primary load bearing components in the plant cell wall, the pectin matrix and the cellulose/xyloglucan network, are constantly remodelled to generate the morphological changes required during plant development. This remodelling is regulated by a plethora of loosening and stiffening agents such as pectin methyl-esterases, calcium ions, expansins, and glucanases. The tight spatio-temporal regulation of the activities of these agents is a sine qua non condition for proper morphogenesis at cell and tissue levels. The pectin matrix and the cellulose-xyloglucan network operate in concert and their behaviour is mutually dependent on their chemical, structural and mechanical modifications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Exploring bacteria-induced growth and morphogenesis in the green macroalga order Ulvales (Chlorophyta

    Directory of Open Access Journals (Sweden)

    Thomas eWichard

    2015-03-01

    Full Text Available Green macroalgae, such as Ulvales, lose their typical morphology completely when grown under axenic conditions or in the absence of the appropriate microbiome. As a result, slow growing aberrant phenotypes or even callus-like morphotypes are observed in Ulvales. The cross-kingdom interactions between marine algae and microorganisms are hence not only restricted by the exchange of macronutrients, including vitamins and nutrients, but also by infochemicals such as bacterial morphogenetic compounds. The latter are a fundamental trait mediating the mutualism within the chemosphere where the organisms interact with each other via compounds in their surroundings.Approximately 60 years ago, pilot studies demonstrated that certain bacteria promote growth, whereas other bacteria induce morphogenesis; this is particularly true for the order of Ulvales. However, only slow progress was made towards the underlying mechanism due to the complexity of, for example, algal cultivation techniques, and the lack of standardized experiments in the laboratory.A breakthrough in this research was the discovery of the morphogenetic compound thallusin, which was isolated from an epiphytic bacterium and induces normal germination and restores the foliaceous morphotypes of Monostroma. Owing to the low concentration, the purification and structure elucidation of highly biologically active morphogenetic compounds is still challenging. Recently, it was found that only the combination of two specific bacteria from the Rhodobacteraceae and Flavobacteriaceae can completely recover the growth and morphogenesis of axenic Ulva mutabilis cultures forming a symbiotic tripartite community by chemical communication.This review combines literature detailing evidence of bacteria-induced morphogenesis in Ulvales. A set of standardized experimental approaches is further proposed for the preparation of axenic algal tissues, bacteria isolation, co-cultivation experiments, and the analysis of

  2. Time-lapse analysis and mathematical characterization elucidate novel mechanisms underlying muscle morphogenesis.

    Directory of Open Access Journals (Sweden)

    Chelsi J Snow

    2008-10-01

    Full Text Available Skeletal muscle morphogenesis transforms short muscle precursor cells into long, multinucleate myotubes that anchor to tendons via the myotendinous junction (MTJ. In vertebrates, a great deal is known about muscle specification as well as how somitic cells, as a cohort, generate the early myotome. However, the cellular mechanisms that generate long muscle fibers from short cells and the molecular factors that limit elongation are unknown. We show that zebrafish fast muscle fiber morphogenesis consists of three discrete phases: short precursor cells, intercalation/elongation, and boundary capture/myotube formation. In the first phase, cells exhibit randomly directed protrusive activity. The second phase, intercalation/elongation, proceeds via a two-step process: protrusion extension and filling. This repetition of protrusion extension and filling continues until both the anterior and posterior ends of the muscle fiber reach the MTJ. Finally, both ends of the muscle fiber anchor to the MTJ (boundary capture and undergo further morphogenetic changes as they adopt the stereotypical, cylindrical shape of myotubes. We find that the basement membrane protein laminin is required for efficient elongation, proper fiber orientation, and boundary capture. These early muscle defects in the absence of either lamininbeta1 or laminingamma1 contrast with later dystrophic phenotypes in lamininalpha2 mutant embryos, indicating discrete roles for different laminin chains during early muscle development. Surprisingly, genetic mosaic analysis suggests that boundary capture is a cell-autonomous phenomenon. Taken together, our results define three phases of muscle fiber morphogenesis and show that the critical second phase of elongation proceeds by a repetitive process of protrusion extension and protrusion filling. Furthermore, we show that laminin is a novel and critical molecular cue mediating fiber orientation and limiting muscle cell length.

  3. Transgenic Expression of Constitutively Active RAC1 Disrupts Mouse Rod Morphogenesis

    Science.gov (United States)

    Song, Hongman; Bush, Ronald A.; Vijayasarathy, Camasamudram; Fariss, Robert N.; Kjellstrom, Sten; Sieving, Paul A.

    2014-01-01

    Purpose. Dominant-active RAC1 rescues photoreceptor structure in Drosophila rhodopsin-null mutants, indicating an important role in morphogenesis. This report assesses the morphogenetic effect of activated RAC1 during mammalian rod photoreceptor development using transgenic mice that express constitutively active (CA) RAC1. Methods. Transgenic mice were generated by expressing CA RAC1 under control of the Rhodopsin promoter, and morphological features of the photoreceptors were evaluated by histology, immunohistochemistry, and transmission electron microscopy. Function was evaluated by electroretinography. Potential protein partners of CA RAC1 were identified by co-immunoprecipitation of retinal extracts. Results. Constitutively active RAC1 expression in differentiating rods disrupted outer retinal lamination as early as postnatal day (P)6, and many photoreceptor cell nuclei were displaced apically into the presumptive subretinal space. These photoreceptors did not develop normal inner and outer segments and had abnormal placement of synaptic elements. Some photoreceptor nuclei were also mislocalized into the inner nuclear layer. Extensive photoreceptor degeneration was subsequently observed in the adult animal. Constitutively active RAC1 formed a complex with the polarity protein PAR6 and with microtubule motor dynein in mouse retina. The normal localization of the PAR6 complex was disrupted in CA RAC1-expressing rod photoreceptors. Conclusions. Constitutively active RAC1 had a profound negative effect on mouse rod cell viability and development. Rod photoreceptors in the CA RAC1 retina exhibited a defect in polarity and migration. Constitutively active RAC1 disrupted rod morphogenesis and gave a phenotype resembling that found in the Crumbs mutant. PAR6 and dynein are two potential downstream effectors that may be involved in CA RAC1-mediated defective mouse photoreceptor morphogenesis. PMID:24651551

  4. Exploring bacteria-induced growth and morphogenesis in the green macroalga order Ulvales (Chlorophyta)

    Science.gov (United States)

    Wichard, Thomas

    2015-01-01

    Green macroalgae, such as Ulvales, lose their typical morphology completely when grown under axenic conditions or in the absence of the appropriate microbiome. As a result, slow growing aberrant phenotypes or even callus-like morphotypes are observed in Ulvales. The cross-kingdom interactions between marine algae and microorganisms are hence not only restricted by the exchange of macronutrients, including vitamins and nutrients, but also by infochemicals such as bacterial morphogenetic compounds. The latter are a fundamental trait mediating the mutualism within the chemosphere where the organisms interact with each other via compounds in their surroundings. Approximately 60 years ago, pilot studies demonstrated that certain bacteria promote growth, whereas other bacteria induce morphogenesis; this is particularly true for the order of Ulvales. However, only slow progress was made towards the underlying mechanism due to the complexity of, for example, algal cultivation techniques, and the lack of standardized experiments in the laboratory. A breakthrough in this research was the discovery of the morphogenetic compound thallusin, which was isolated from an epiphytic bacterium and induces normal germination restoring the foliaceous morphotypes of Monostroma. Owing to the low concentration, the purification and structure elucidation of highly biologically active morphogenetic compounds are still challenging. Recently, it was found that only the combination of two specific bacteria from the Rhodobacteraceae and Flavobacteriaceae can completely recover the growth and morphogenesis of axenic Ulva mutabilis cultures forming a symbiotic tripartite community by chemical communication. This review combines literature detailing evidences of bacteria-induced morphogenesis in Ulvales. A set of standardized experimental approaches is further proposed for the preparation of axenic algal tissues, bacteria isolation, co-cultivation experiments, and the analysis of the chemosphere

  5. Morphogenesis and calcification of the statoconia in the chick (Gallus domesticus) embryo - Implications for future studies

    Science.gov (United States)

    Fermin, C. D.; Igarashi, M.

    1985-01-01

    The morphogenesis of the statoconia in the chick, Gallus domesticus, injected with a carbon anhydrase inhibitor is studied. The preparation of the embryo specimens for analysis is described. The early, middle, and late stages of embryonic development are examined. The data reveal that acetozolamide inhibits statoconia formation in the middle stage of development and the calcification process follows statoconia formation. The spatial relationship between the development of type 1 and type 2 hair cells and the appearance and maturation of the statoconia is investigated.

  6. Bicaudal C1 promotes pancreatic NEUROG3+ endocrine progenitor differentiation and ductal morphogenesis

    DEFF Research Database (Denmark)

    Lemaire, Laurence A; Goulley, Joan; Kim, Yung Hae

    2015-01-01

    that line the ducts during development, and in the ducts after birth, but not in differentiated endocrine or acinar cells. Genetic inactivation of Bicc1 leads to ductal cell over-proliferation and cyst formation. Transcriptome comparison between WT and Bicc1 KO pancreata, before the phenotype onset, reveals......(+) endocrine progenitor production. Its deletion leads to a late but sustained endocrine progenitor decrease, resulting in a 50% reduction of endocrine cells. We show that BICC1 functions downstream of ONECUT1 in the pathway controlling both NEUROG3(+) endocrine cell production and ductal morphogenesis...

  7. The DCL gene of tomato is required for chloroplast development and palisade cell morphogenesis in leaves.

    OpenAIRE

    Keddie, J S; Carroll, B; Jones, J D; Gruissem, W

    1996-01-01

    The defective chloroplasts and leaves-mutable (dcl-m) mutation of tomato was identified in a Ds mutagenesis screen. This unstable mutation affects both chloroplast development and palisade cell morphogenesis in leaves. Mutant plants are clonally variegated as a result of somatic excision of Ds and have albino leaves with green sectors. Leaf midribs and stems are light green with sectors of dark green tissue but fruit and petals are wild-type in appearance. Within dark green sectors of dcl-m l...

  8. Signalling in the epidermis: the E2F cell cycle regulatory pathway in epidermal morphogenesis, regeneration and transformation.

    Science.gov (United States)

    Ivanova, Iordanka A; D'Souza, Sudhir J A; Dagnino, Lina

    2005-01-01

    The epidermis is the outermost layer in the skin, and it is the first line of defence against the environment. The epidermis also provides a barrier against loss of fluids and electrolytes, which is crucial for life. Essential in the maintenance of this tissue is its ability to continually self-renew and regenerate after injury. These two characteristics are critically dependent on the ability of the principal epidermal cell type, the keratinocyte, to proliferate and to respond to differentiation cues. Indeed, the epidermis is a multilayered tissue composed of keratinocyte stem cells and their differentiated progeny. Central for the control of cell proliferation is the E2F transcription factor regulatory network. This signaling network also includes cyclins, cdk, cdk inhibitors and the retinoblastoma (pRb) family of proteins. The biological importance of the E2F/pRb pathway is emphasized by the fact that a majority of human tumours exhibit alterations that disrupt the ability of pRb proteins to inhibit E2F, leading to permanent activation of the latter. Further, E2F is essential for normal epidermal regeneration after injury. Other member of the E2F signaling pathway are also involved in epidermal development and pathophysiology. Thus, whereas the pRb family of proteins is essential for epidermal morphogenesis, abnormal regulation of cyclins and E2F proteins results in tumorgenesis in this tissue. In this review, we discuss the role of each member of this important growth regulatory network in epidermal formation, homeostasis and carcinogenesis.

  9. Ingestion of BioCell Collagen®, a novel hydrolyzed chicken sternal cartilage extract; enhanced blood microcirculation and reduced facial aging signs

    Directory of Open Access Journals (Sweden)

    Schwartz SR

    2012-07-01

    Full Text Available Stephen R Schwartz,1 Joosang Park21International Research Services Inc, Port Chester, NY, USA; 2BioCell Technology, LLC, Newport Beach, CA, USAAbstract: Skin aging and its clinical manifestation is associated with altered molecular metabolism in the extracellular matrix of the dermis. In a pilot open-label study, we investigated the effect of a dietary supplement, BioCell Collagen® (BCC, which contains a naturally occurring matrix of hydrolyzed collagen type II and low-molecular-weight hyaluronic acid and chondroitin sulfate, in 26 healthy females who displayed visible signs of natural and photoaging in the face. Daily supplementation with 1 g of BCC for 12 weeks led to a significant reduction of skin dryness/scaling (76%, P = 0.002 and global lines/wrinkles (13.2%, P = 0.028 as measured by visual/tactile score. Additionally, a significant increase in the content of hemoglobin (17.7%, P = 0.018 and collagen (6.3%, P = 0.002 in the skin dermis was observed after 6 weeks of supplementation. At the end of the study, the increase in hemoglobin remained significant (15%, P = 0.008, while the increase in collagen content was maintained, but the difference from baseline was not significant (3.5%, P = 0.134. This study provides preliminary data suggesting that dietary supplementation with BCC elicits several physiological events which can be harnessed to counteract natural photoaging processes to reduce visible aging signs in the human face. A controlled study is necessary to verify these observations.Keywords: BioCell Collagen, chicken sternal cartilage extract, hydrolyzed collagen type II, low-molecular-weight hyaluronic acid, skin aging

  10. Comparison of the effects of sternal and tibial intraosseous administered resuscitative drugs on return of spontaneous circulation in a swine model of cardiac arrest.

    Science.gov (United States)

    O'Sullivan, Mara; Martinez, Andre; Long, Audrey; Johnson, Michelle; Blouin, Dawn; Johnson, Arthur D; Burgert, James M

    2016-01-01

    Compare vasopressin, amiodarone, and epinephrine administration by sternal intraosseous (SIO), tibial intraosseous (TIO), and intravenous (IV) routes in a swine model of cardiac arrest. Prospective, randomized, between subjects, experimental design. Laboratory. Male Yorkshire-cross swine (N = 35), seven per group. Swine were randomized to SIO, TIO, IV, cardiopulmonary resuscitation (CPR) with defibrillation, or CPR-only groups. Ventricular fibrillation (VF) was induced under general anesthesia. Mechanical CPR began 2 minutes postarrest. Vasopressin (40 U) was administered to the SIO, TIO, and IV groups 4 minutes postarrest. Defibrillation was performed and amiodarone (300 mg) was administered 6 minutes postarrest. Defibrillation was repeated, and epinephrine (1 mg) was administered 10 minutes postarrest. Defibrillation was repeated every 2 minutes and epinephrine repeated every 4 minutes until return of spontaneous circulation (ROSC) or 26 postarrest minutes elapsed. Rate of ROSC, time to ROSC, and odds of ROSC. There were no significant differences in rate of ROSC between the SIO and TIO (p = 0.22) or IV groups (p = 1.0). Time to ROSC was five times less in the SIO group than the TIO group (p = 0.003) but not compared to IV (p = 0.125). Time to ROSC in the IV group was significantly less than the TIO group (p = 0.04). Odds of ROSC for the SIO group were five times higher compared to the TIO group but same as IV. Odds of ROSC in the IV group were higher than the TIO group. There was a statistically significant delay in the time to ROSC and a clinically significant difference in odds of ROSC when resuscitative drugs, including lipophilic amiodarone, were administered by the TIO route compared to the SIO and IV routes in a swine model of sudden cardiac arrest. Further investigations are warranted to isolate the mechanism behind these findings.

  11. Primary cilia function regulates the length of the embryonic trunk axis and urogenital field in mice

    DEFF Research Database (Denmark)

    Wainwright, Elanor N.; Svingen, Terje; Ting Ng, Ee

    2014-01-01

    The issues of whether and how some organs coordinate their size and shape with the blueprint of the embryo axis, while others appear to regulate their morphogenesis autonomously, remain poorly understood. Mutations in Ift144, encoding a component of the trafficking machinery of primary cilia asse...

  12. Spatiotemporal mechanical variation reveals critical role for rho kinase during primitive streak morphogenesis.

    Science.gov (United States)

    Henkels, Julia; Oh, Jaeho; Xu, Wenwei; Owen, Drew; Sulchek, Todd; Zamir, Evan

    2013-02-01

    Large-scale morphogenetic movements during early embryo development are driven by complex changes in biochemical and biophysical factors. Current models for amniote primitive streak morphogenesis and gastrulation take into account numerous genetic pathways but largely ignore the role of mechanical forces. Here, we used atomic force microscopy (AFM) to obtain for the first time precise biomechanical properties of the early avian embryo. Our data reveal that the primitive streak is significantly stiffer than neighboring regions of the epiblast, and that it is stiffer than the pre-primitive streak epiblast. To test our hypothesis that these changes in mechanical properties are due to a localized increase of actomyosin contractility, we inhibited actomyosin contractility via the Rho kinase (ROCK) pathway using the small-molecule inhibitor Y-27632. Our results using several different assays show the following: (1) primitive streak formation was blocked; (2) the time-dependent increase in primitive streak stiffness was abolished; and (3) convergence of epiblast cells to the midline was inhibited. Taken together, our data suggest that actomyosin contractility is necessary for primitive streak morphogenesis, and specifically, ROCK plays a critical role. To better understand the underlying mechanisms of this fundamental process, future models should account for the findings presented in this study.

  13. Micro/nano-computed tomography technology for quantitative dynamic, multi-scale imaging of morphogenesis.

    Science.gov (United States)

    Gregg, Chelsea L; Recknagel, Andrew K; Butcher, Jonathan T

    2015-01-01

    Tissue morphogenesis and embryonic development are dynamic events challenging to quantify, especially considering the intricate events that happen simultaneously in different locations and time. Micro- and more recently nano-computed tomography (micro/nanoCT) has been used for the past 15 years to characterize large 3D fields of tortuous geometries at high spatial resolution. We and others have advanced micro/nanoCT imaging strategies for quantifying tissue- and organ-level fate changes throughout morphogenesis. Exogenous soft tissue contrast media enables visualization of vascular lumens and tissues via extravasation. Furthermore, the emergence of antigen-specific tissue contrast enables direct quantitative visualization of protein and mRNA expression. Micro-CT X-ray doses appear to be non-embryotoxic, enabling longitudinal imaging studies in live embryos. In this chapter we present established soft tissue contrast protocols for obtaining high-quality micro/nanoCT images and the image processing techniques useful for quantifying anatomical and physiological information from the data sets.

  14. Molecular Biology of Feather Morphogenesis: A Testable Model for Evo-Devo Research

    Science.gov (United States)

    WIDELITZ, RANDALL B.; JIANG, TING XIN; YU, MINGKE; SHEN, TED; SHEN, JEN-YEE; WU, PING; YU, ZHICAO; CHUONG, CHENG-MING

    2015-01-01

    Darwin’s theory describes the principles that are responsible for evolutionary change of organisms and their attributes. The actual mechanisms, however, need to be studied for each species and each organ separately. Here we have investigated the mechanisms underlying these principles in the avian feather. Feathers comprise one of the most complex and diverse epidermal organs as demonstrated by their shape, size, patterned arrangement and pigmentation. Variations can occur at several steps along each level of organization, leading to highly diverse forms and functions. Feathers develop gradually during ontogeny through a series of steps that may correspond to the evolutionary steps that were taken during the phylogeny from a reptilian ancestor to birds. These developmental steps include 1) the formation of feather tract fields on the skin surfaces; 2) periodic patterning of the individual feather primordia within the feather tract fields; 3) feather bud morphogenesis establishing anterio - posterior (along the cranio - caudal axis) and proximo - distal axes; 4) branching morphogenesis to create the rachis, barbs and barbules within a feather bud; and 5) gradual modulations of these basic morphological parameters within a single feather or across a feather tract. Thus, possibilities for variation in form and function of feathers occur at every developmental step. In this paper, principles guiding feather tract formation, distributions of individual feathers within the tracts and variations in feather forms are discussed at a cellular and molecular level. PMID:12949772

  15. TMEM45A Is Dispensable for Epidermal Morphogenesis, Keratinization and Barrier Formation.

    Directory of Open Access Journals (Sweden)

    Aurélie Hayez

    Full Text Available TMEM45A gene encodes an initially uncharacterized predicted transmembrane protein. We previously showed that this gene is highly expressed in keratinocytes where its expression correlates with keratinization, suggesting a role in normal epidermal physiology. To test this hypothesis, we generated TMEM45A knockout mice and found that these mice develop without any evident phenotype. The morphology of the epidermis assessed by histology and by labelling differentiation markers in immunofluorescence was not altered. Toluidine blue permeability assay showed that the epidermal barrier develops normally during embryonic development. We also showed that depletion of TMEM45A in human keratinocytes does not alter their potential to form in vitro 3D-reconstructed epidermis. Indeed, epidermis with normal morphogenesis were generated from TMEM45A-silenced keratinocytes. Their expression of differentiation markers quantified by RT-qPCR and evidenced by immunofluorescence labelling as well as their barrier function estimated by Lucifer yellow permeability were similar to the control epidermis. In summary, TMEM45A gene expression is dispensable for epidermal morphogenesis, keratinization and barrier formation. If this protein plays a role in the epidermis, its experimental depletion can possibly be compensated by other proteins in the two experimental models analyzed in this study.

  16. Influence of plasmogenes on the productivity of morphogenesis in strawberry (Fragaria x ananassa Duch.

    Directory of Open Access Journals (Sweden)

    Jadwiga Żebrowska

    2012-12-01

    Full Text Available Plasmogenes are largely located in mitochondria or plastids and they can influence the inheritance of many plant characteristics. This phenomenon is called cytoplasmic inheritance and can be detected on the basis of the expression of a trait in progeny F1 obtained from single and reciprocal crosses. The aim of this study was to examine the cytoplasmic inheritance of in vitro productivity of morphogenesis in three genotypes of Fragaria x ananassa Duch., i.e. the cultivars 'Dukat', 'Teresa' and the breeding clone no. 590. Single and reciprocal crosses were done according to Griffi ng's method 3. The value of general combining ability (GCA indicated cv. 'Teresa' as the best maternal component for crossing and 'Dukat' as the worst. The negative reciprocal cross effects (rij revealed the cytoplasmic inheritance for cv. 'Dukat' as maternal form and positive rij for the breeding clone no. 590 indicated the nuclear inheritance of morphogenetic ability. Cv. 'Teresa', as maternal component, showed nuclear inheritance of that trait in crossing with cv. 'Dukat' and with 590 cytoplasmic inheritance. The productivity of morphogenesis in strawberry depended on the parental combination and the direction of crossing.

  17. Programmed Cell-to-Cell Variability in Ras Activity Triggers Emergent Behaviors during Mammary Epithelial Morphogenesis

    Directory of Open Access Journals (Sweden)

    Jennifer S. Liu

    2012-11-01

    Full Text Available Variability in signaling pathway activation between neighboring epithelial cells can arise from local differences in the microenvironment, noisy gene expression, or acquired genetic changes. To investigate the consequences of this cell-to-cell variability in signaling pathway activation on coordinated multicellular processes such as morphogenesis, we use DNA-programmed assembly to construct three-dimensional MCF10A microtissues that are mosaic for low-level expression of activated H-Ras. We find two emergent behaviors in mosaic microtissues: cells with activated H-Ras are basally extruded or lead motile multicellular protrusions that direct the collective motility of their wild-type neighbors. Remarkably, these behaviors are not observed in homogeneous microtissues in which all cells express the activated Ras protein, indicating that heterogeneity in Ras activity, rather than the total amount of Ras activity, is critical for these processes. Our results directly demonstrate that cell-to-cell variability in pathway activation within local populations of epithelial cells can drive emergent behaviors during epithelial morphogenesis.

  18. p38α MAPK Is Required for Tooth Morphogenesis and Enamel Secretion*

    Science.gov (United States)

    Greenblatt, Matthew B.; Kim, Jung-Min; Oh, Hwanhee; Park, Kwang Hwan; Choo, Min-Kyung; Sano, Yasuyo; Tye, Coralee E.; Skobe, Ziedonis; Davis, Roger J.; Park, Jin Mo; Bei, Marianna; Glimcher, Laurie H.; Shim, Jae-Hyuck

    2015-01-01

    An improved understanding of the molecular pathways that drive tooth morphogenesis and enamel secretion is needed to generate teeth from organ cultures for therapeutic implantation or to determine the pathogenesis of primary disorders of dentition (Abdollah, S., Macias-Silva, M., Tsukazaki, T., Hayashi, H., Attisano, L., and Wrana, J. L. (1997) J. Biol. Chem. 272, 27678–27685). Here we present a novel ectodermal dysplasia phenotype associated with conditional deletion of p38α MAPK in ectodermal appendages using K14-cre mice (p38αK14 mice). These mice display impaired patterning of dental cusps and a profound defect in the production and biomechanical strength of dental enamel because of defects in ameloblast differentiation and activity. In the absence of p38α, expression of amelogenin and β4-integrin in ameloblasts and p21 in the enamel knot was significantly reduced. Mice lacking the MAP2K MKK6, but not mice lacking MAP2K MKK3, also show the enamel defects, implying that MKK6 functions as an upstream kinase of p38α in ectodermal appendages. Lastly, stimulation with BMP2/7 in both explant culture and an ameloblast cell line confirm that p38α functions downstream of BMPs in this context. Thus, BMP-induced activation of the p38α MAPK pathway is critical for the morphogenesis of tooth cusps and the secretion of dental enamel. PMID:25406311

  19. Morphology, morphogenesis, and phylogeny of an Anteholosticha intermedia (Ciliophora, Urostylida) population from the United States.

    Science.gov (United States)

    Chen, Lingyun; Wu, Weining; El-Serehy, Hamed A; Hu, Xiaozhong; Clamp, John C

    2018-04-30

    A distinct population of Anteholosticha intermedia was isolated from soil in the Great Smoky Mountains of North Carolina, USA, and its morphology, morphogenesis and molecular phylogeny investigated by microscopic observations of live and protargol-prepared specimens and analyses of the sequence of small subunit (SSU) rDNA. Our population closely resembles the populations from Austria and Korea. Members of the genus Anteholosticha have been regarded as ontogenetically diverse, which is confirmed by the present work. The most noteworthy ontogenetic feature of the American population of A. intermedia is that the oral primordium in the proter appears apokinetally at the posterior end of the undulating membranes anlage at the beginning of division and then dedifferentiates midway through morphogenesis. Molecular phylogenetic analyses demonstrate, with high support, that the American population of A. intermedia is clearly distinct from congeners and branches as part of a sister lineage to the Bakuella-Urostyla clade that belongs to the major clade comprising the order Urostylida. Copyright © 2018 Elsevier GmbH. All rights reserved.

  20. Identifying the cellular mechanisms of symbiont-induced epithelial morphogenesis in the squid-Vibrio association.

    Science.gov (United States)

    Koropatnick, Tanya; Goodson, Michael S; Heath-Heckman, Elizabeth A C; McFall-Ngai, Margaret

    2014-02-01

    The symbiotic association between the Hawaiian bobtail squid Euprymna scolopes and the luminous marine bacterium Vibrio fischeri provides a unique opportunity to study epithelial morphogenesis. Shortly after hatching, the squid host harvests bacteria from the seawater using currents created by two elaborate fields of ciliated epithelia on the surface of the juvenile light organ. After light organ colonization, the symbiont population signals the gradual loss of the ciliated epithelia through apoptosis of the cells, which culminates in the complete regression of these tissues. Whereas aspects of this process have been studied at the morphological, biochemical, and molecular levels, no in-depth analysis of the cellular events has been reported. Here we describe the cellular structure of the epithelial field and present evidence that the symbiosis-induced regression occurs in two steps. Using confocal microscopic analyses, we observed an initial epithelial remodeling, which serves to disable the function of the harvesting apparatus, followed by a protracted regression involving actin rearrangements and epithelial cell extrusion. We identified a metal-dependent gelatinolytic activity in the symbiont-induced morphogenic epithelial fields, suggesting the involvement of Zn-dependent matrix metalloproteinase(s) (MMP) in light organ morphogenesis. These data show that the bacterial symbionts not only induce apoptosis of the field, but also change the form, function, and biochemistry of the cells as part of the morphogenic program.

  1. A Transient Exposure to Symbiosis-Competent Bacteria Induces Light Organ Morphogenesis in the Host Squid.

    Science.gov (United States)

    Doino, J A; McFall-Ngai, M J

    1995-12-01

    Recent studies of the symbiotic association between the Hawaiian sepiolid squid Euprymna scolopes and the luminous bacterium Vibrio fischeri have shown that colonization of juvenile squid with symbiosis-competent bacteria induces morphogenetic changes of the light organ. These changes occur over a 4-day period and include cell death and tissue regression of the external ciliated epithelium. In the absence of bacterial colonization, morphogenesis does not occur. To determine whether the bacteria must be present throughout the morphogenetic process, we used the antibiotic chloramphenicol to clear the light organ of bacteria at various times during the initial colonization. We provide evidence in this study that a transient, 12-hour exposure to symbiosis-competent bacteria is necessary and sufficient to induce tissue regression in the light organ over the next several days. Further, we show that successful entrance into the light organ is necessary to induce morphogenesis, suggesting that induction results from bacterial interaction with internal crypt cells and not with the external ciliated epithelium. Finally, no difference in development was observed when the light organ was colonized by a mutant strain of V. fischeri that did not produce autoinducer, a potential light organ morphogen.

  2. Over-expression of KdSOC1 gene affected plantlet morphogenesis in Kalanchoe daigremontiana.

    Science.gov (United States)

    Zhu, Chen; Wang, Li; Chen, Jinhua; Liu, Chenglan; Zeng, Huiming; Wang, Huafang

    2017-07-17

    Kalanchoe daigremontiana reproduces asexually by producing plantlets along the leaf margin. The aim of this study was to identify the function of the SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 gene in Kalanchoe daigremontiana (KdSOC1) during plantlet morphogenesis. In this study, KdSOC1 gene expression was detected at stem cell niche during in vitro somatic embryogenesis and plantlet morphogenesis. Disrupting endogenous auxin transportation suppressed the KdSOC1 gene response. Knockdown of the KdSOC1 gene caused a defect in cotyledon formation during the early heart stage of somatic embryogenesis. Over-expression (OE) of the KdSOC1 gene resulted in asymmetric plantlet distribution, a reduced number of plantlets, thicker leaves, and thicker vascular fibers. Higher KdPIN1 gene expression and auxin content were found in OE plant compared to those of wild-type plant leaves, which indicated possible KdSOC1 gene role in affecting auxin distribution and accumulation. KdSOC1 gene OE in DR5-GUS Arabidopsis reporting lines resulted in an abnormal auxin response pattern during different stages of somatic embryogenesis. In summary, the KdSOC1 gene OE might alter auxin distribution and accumulation along leaf margin to initiate plantlet formation and distribution, which is crucial for plasticity during plantlet formation under various environmental conditions.

  3. Gonad morphogenesis defects drive hybrid male sterility in asymmetric hybrid breakdown of Caenorhabditis nematodes.

    Science.gov (United States)

    Dey, Alivia; Jin, Qi; Chen, Yen-Chu; Cutter, Asher D

    2014-01-01

    Determining the causes and evolution of reproductive barriers to gene flow between populations, speciation, is the key to understanding the origin of diversity in nature. Many species manifest hybrid breakdown when they intercross, characterized by increasingly exacerbated problems in later generations of hybrids. Recently, Caenorhabditis nematodes have emerged as a genetic model for studying speciation, and here we investigate the nature and causes of hybrid breakdown between Caenorhabditis remanei and C. latens. We quantify partial F1 hybrid inviability and extensive F2 hybrid inviability; the ~75% F2 embryonic arrest occurs primarily during gastrulation or embryonic elongation. Moreover, F1 hybrid males exhibit Haldane's rule asymmetrically for both sterility and inviability, being strongest when C. remanei serves as maternal parent. We show that the mechanism by which sterile hybrid males are incapable of transferring sperm or a copulatory plug involves defective gonad morphogenesis, which we hypothesize results from linker cell defects in migration and/or cell death during development. This first documented case of partial hybrid male sterility in Caenorhabditis follows expectations of Darwin's corollary to Haldane's rule for asymmetric male fitness, providing a powerful foundation for molecular dissection of intrinsic reproductive barriers and divergence of genetic pathways controlling organ morphogenesis. © 2014 Wiley Periodicals, Inc.

  4. Plant morphogenesis, auxin, and the signal-trafficking network incompleteness theorem

    Directory of Open Access Journals (Sweden)

    Karl J. Niklas

    2012-03-01

    Full Text Available Plant morphogenesis (the development of form and function requires signal-trafficking and cross-talking among all levels of organization to coordinate the operation of metabolic and genomic networked systems. Many if not all of these biological features can be rendered as logic circuits supervising the operation of one or more signal-activated metabolic or genome networks. This approach simplifies complex morphogenetic phenomena and allows for their aggregation into diagrams of larger, more "global" networked systems. This conceptualization is illustrated for morphogenesis in model plants such as maize (Zea mays and Thale cress (Arabidopsis thaliana from an evolutionary perspective. The phytohormone indole-acetic acid (IAA is used as an example for a well-known signaling chemical and discussed in terms of the logic circuits and signal-activated sub-systems for hormone-mediated wall loosening and cell expansion as well as polar/lateral intercellular IAA transport. For each of these phenomena, a circuit/sub-system diagram highlights missing components, either in the logic circuit or in the sub-system it supervises, that must be identified experimentally if each of these basic phenomena is to be fully understood within a phylogen

  5. ABA content in shoots and roots of pea mutants af and tl as related to their growth and morphogenesis

    Czech Academy of Sciences Publication Activity Database

    Kof, E.M.; Vinogradova, I.A.; Oorzhak, A.S.; Karyagin, V.V.; Kalibernaya, Z.V.; Macháčková, Ivana; Kondykov, I.V.; Chuvasheva, E.S.

    2006-01-01

    Roč. 53, č. 3 (2006), s. 359-365 ISSN 1021-4437 Institutional research plan: CEZ:AV0Z50380511 Keywords : Pisum sativum * af and tl leaf mutants * morphogenesis Subject RIV: EF - Botanics Impact factor: 0.321, year: 2006

  6. A novel cell binding site in the coiled‐coil domain of laminin involved in capillary morphogenesis

    DEFF Research Database (Denmark)

    Sanz, Laura; García-Bermejo, Laura; Blanco, Francisco J

    2003-01-01

    Recently, we reported the isolation and characterization of an anti‐laminin antibody that modulates the extracellular matrix‐dependent morphogenesis of endothelial cells. Here we use this antibody to precisely map the binding site responsible for mediating this biologically important interaction....

  7. Multidisciplinary Inquiry-Based Investigation Learning Using an Ex Ovo Chicken Culture Platform: Role of Vitamin A on Embryonic Morphogenesis

    Science.gov (United States)

    Buskohl, Philip R.; Gould, Russell A.; Curran, Susan; Archer, Shivaun D.; Butcher, Jonathan T.

    2012-01-01

    Embryonic development offers a unique perspective on the function of many biological processes because of embryos' heightened sensitivity to environmental factors. This hands-on lesson investigates the effects of elevated vitamin A on the morphogenesis of chicken embryos. The active form of vitamin A (retinoic acid) is applied to shell-less (ex…

  8. Full-length fibronectin drives fibroblast accumulation at the surface of collagen microtissues during cell-induced tissue morphogenesis

    NARCIS (Netherlands)

    Foolen, J.; Shiu, J.-Y.; Mitsi, M.; Zhang, Y.; Chen, C.; Vogel, Viola

    2016-01-01

    Generating and maintaining gradients of cell density and extracellular matrix (ECM) components is a prerequisite for the development of functionality of healthy tissue. Therefore, gaining insights into the drivers of spatial organization of cells and the role of ECM during tissue morphogenesis is

  9. Comparative Transcriptome Analysis of Fetal Skin Reveals Key Genes Related to Hair Follicle Morphogenesis in Cashmere Goats.

    Directory of Open Access Journals (Sweden)

    Ye Gao

    Full Text Available Cashmere goat skin contains two types of hair follicles (HF: primary hair follicles (PHF and secondary hair follicles (SHF. Although multiple genetic determinants associated with HF formation have been identified, the molecules that determine the independent morphogenesis of HF in cashmere goats remain elusive. The growth and development of SHF directly influence the quantity and quality of cashmere production. Here, we report the transcriptome profiling analysis of nine skin samples from cashmere goats using 60- and 120-day-old embryos (E60 and E120, respectively, as well as newborns (NB, through RNA-sequencing (RNA-seq. HF morphological changes indicated that PHF were initiated at E60, with maturation from E120, while differentiation of SHF was identified at E120 until formation of cashmere occurred after birth (NB. The RNA-sequencing analysis generated over 20.6 million clean reads from each mRNA library. The number of differentially expressed genes (DEGs in E60 vs. E120, E120 vs. NB, and E60 vs. NB were 1,024, 0 and 1,801, respectively, indicating that no significant differences were found at transcriptomic levels between E120 and NB. Key genes including B4GALT4, TNC, a-integrin, and FGFR1, were up-regulated and expressed in HF initiation from E60 to E120, while regulatory genes such as GPRC5D, PAD3, HOXC13, PRR9, VSIG8, LRRC15, LHX2, MSX-2, and FOXN1 were up-regulated and expressed in HF keratinisation and hair shaft differentiation from E120 and NB to E60. Several genes belonging to the KRT and KRTAP gene families were detected throughout the three HF developmental stages. The transcriptional trajectory analyses of all DEGs indicated that immune privilege, glycosaminoglycan biosynthesis, extracellular matrix receptor interaction, and growth factor receptors all played dominant roles in the epithelial-mesenchymal interface and HF formation. We found that the Wnt, transforming growth factor-beta/bone morphogenetic protein, and Notch family

  10. Comparative Transcriptome Analysis of Fetal Skin Reveals Key Genes Related to Hair Follicle Morphogenesis in Cashmere Goats.

    Science.gov (United States)

    Gao, Ye; Wang, Xiaolong; Yan, Hailong; Zeng, Jie; Ma, Sen; Niu, Yiyuan; Zhou, Guangxian; Jiang, Yu; Chen, Yulin

    2016-01-01

    Cashmere goat skin contains two types of hair follicles (HF): primary hair follicles (PHF) and secondary hair follicles (SHF). Although multiple genetic determinants associated with HF formation have been identified, the molecules that determine the independent morphogenesis of HF in cashmere goats remain elusive. The growth and development of SHF directly influence the quantity and quality of cashmere production. Here, we report the transcriptome profiling analysis of nine skin samples from cashmere goats using 60- and 120-day-old embryos (E60 and E120, respectively), as well as newborns (NB), through RNA-sequencing (RNA-seq). HF morphological changes indicated that PHF were initiated at E60, with maturation from E120, while differentiation of SHF was identified at E120 until formation of cashmere occurred after birth (NB). The RNA-sequencing analysis generated over 20.6 million clean reads from each mRNA library. The number of differentially expressed genes (DEGs) in E60 vs. E120, E120 vs. NB, and E60 vs. NB were 1,024, 0 and 1,801, respectively, indicating that no significant differences were found at transcriptomic levels between E120 and NB. Key genes including B4GALT4, TNC, a-integrin, and FGFR1, were up-regulated and expressed in HF initiation from E60 to E120, while regulatory genes such as GPRC5D, PAD3, HOXC13, PRR9, VSIG8, LRRC15, LHX2, MSX-2, and FOXN1 were up-regulated and expressed in HF keratinisation and hair shaft differentiation from E120 and NB to E60. Several genes belonging to the KRT and KRTAP gene families were detected throughout the three HF developmental stages. The transcriptional trajectory analyses of all DEGs indicated that immune privilege, glycosaminoglycan biosynthesis, extracellular matrix receptor interaction, and growth factor receptors all played dominant roles in the epithelial-mesenchymal interface and HF formation. We found that the Wnt, transforming growth factor-beta/bone morphogenetic protein, and Notch family members

  11. Streptomyces sporulation - Genes and regulators involved in bacterial cell differentiation

    OpenAIRE

    Larsson, Jessica

    2010-01-01

    Streptomycetes are Gram-positive bacteria with a complex developmental life cycle. They form spores on specialized cells called aerial hyphae, and this sporulation involves alterations in growth, morphogenesis and cell cycle processes like cell division and chromosome segregation. Understanding the developmental mechanisms that streptomycetes have evolved for regulating for example cell division is of general interest in bacterial cell biology. It can also be valuable in the design of new dru...

  12. Microenvironments and Signaling Pathways Regulating Early Dissemination, Dormancy, and Metastasis

    Science.gov (United States)

    2016-09-01

    regulators of branching morphogenesis during mammary gland development 17,18, arguing that normal mammary epithelial cells cooperate with these innate ...CD45+CD11b+F4/80+ cells lacking lymphoid and granulocytic markers (Supplementary Fig.3B). viSNE plots 30 of myelo- monocytic cells (Fig.5A) showed that...cancer cells and how the microenvironment in these primary sites named P-TMEM (Primary Tumor Microenvironment of Metastases) contribute to early

  13. Uncovering the Number and Clonal Dynamics of Mesp1 Progenitors during Heart Morphogenesis

    Directory of Open Access Journals (Sweden)

    Samira Chabab

    2016-01-01

    Full Text Available The heart arises from distinct sources of cardiac progenitors that independently express Mesp1 during gastrulation. The precise number of Mesp1 progenitors that are specified during the early stage of gastrulation, and their clonal behavior during heart morphogenesis, is currently unknown. Here, we used clonal and mosaic tracing of Mesp1-expressing cells combined with quantitative biophysical analysis of the clonal data to define the number of cardiac progenitors and their mode of growth during heart development. Our data indicate that the myocardial layer of the heart derive from ∼250 Mesp1-expressing cardiac progenitors born during gastrulation. Despite arising at different time points and contributing to different heart regions, the temporally distinct cardiac progenitors present very similar clonal dynamics. These results provide insights into the number of cardiac progenitors and their mode of growth and open up avenues to decipher the clonal dynamics of progenitors in other organs and tissues.

  14. Dynamics of cell wall elasticity pattern shapes the cell during yeast mating morphogenesis

    Science.gov (United States)

    Goldenbogen, Björn; Giese, Wolfgang; Hemmen, Marie; Uhlendorf, Jannis; Herrmann, Andreas

    2016-01-01

    The cell wall defines cell shape and maintains integrity of fungi and plants. When exposed to mating pheromone, Saccharomyces cerevisiae grows a mating projection and alters in morphology from spherical to shmoo form. Although structural and compositional alterations of the cell wall accompany shape transitions, their impact on cell wall elasticity is unknown. In a combined theoretical and experimental approach using finite-element modelling and atomic force microscopy (AFM), we investigated the influence of spatially and temporally varying material properties on mating morphogenesis. Time-resolved elasticity maps of shmooing yeast acquired with AFM in vivo revealed distinct patterns, with soft material at the emerging mating projection and stiff material at the tip. The observed cell wall softening in the protrusion region is necessary for the formation of the characteristic shmoo shape, and results in wider and longer mating projections. The approach is generally applicable to tip-growing fungi and plants cells. PMID:27605377

  15. Evolution of experimental deciduomata in the rat: cellular filiation and morphogenesis

    International Nuclear Information System (INIS)

    Dupont, Henri; Sartor, Pierre; Dupont, M.-A.; Duluc, A.-J.; Mayer, Gaston

    1978-01-01

    The morphogenesis of experimental deciduomata and the genesis of polyploidy in this tissue were studied by radioautographic and ultrastructural techniques in the rat. The growth is effected by mitotic renewal of diploid cells which are in post-synthetic resting period. They themselves organize by forming cellular strings. The level of Polyploidy is determined by the modality of division. Mitotic divisions without cytodieresis lead to a substantial pool of binucleated cells (2n + 2n) in mesometrial and antimesometrial areas. Mitotic divisions for binucleated cells with a single spindle can create tetraploid mononucleated cells. This mitotic type of division limits the polyploidy to 4 n in mesometrial cells. In antimesometrial area the evolution continues above 4 n nuclei by means of endomitosis, without any filiation between mono-and binucleated cells. In some respects, this evolution agrees with results obtained in hepatic tissue in the rat [fr

  16. The role of nitric oxide and hemoglobin in plant development and morphogenesis

    DEFF Research Database (Denmark)

    Hebelstrup, Kim; Shah, Jay K; Igamberdiev, Abir U

    2013-01-01

    effects on control of plant growth and development, such as shoot and root architecture. All plants are able to express non-symbiotic hemoglobins at low concentration. Their function is generally not related to oxygen transport or storage; instead they effectively oxidize NO to NO3– and thereby control...... the local cellular NO concentration. In this review, we analyze available data on the role of NO and plant hemoglobins in morphogenetic processes in plants. The comparison of the data suggests that hemoglobin gene expression in plants modulates development and morphogenesis of organs, such as roots...... and shoots, through the localized control of NO, and that hemoglobin gene expression should always be considered a modulating factor in processes controlled directly or indirectly by NO in plants....

  17. Myoepithelial Cells: Their Origin and Function in Lacrimal Gland Morphogenesis, Homeostasis, and Repair.

    Science.gov (United States)

    Makarenkova, Helen P; Dartt, Darlene A

    2015-09-01

    Lacrimal gland (LG) is an exocrine tubuloacinar gland that secretes the aqueous layer of the tear film. LG epithelium is composed of ductal, acinar, and myoepithelial cells (MECs) bordering the basal lamina and separating the epithelial layer from the extracellular matrix. Mature MECs have contractile ability and morphologically resemble smooth muscle cells; however, they exhibit features typical for epithelial cells, such as the presence of specific cytokeratin filaments. Increasing evidence supports the assertion that myoepithelial cells (MECs) play key roles in the lacrimal gland development, homeostasis, and stabilizing the normal structure and polarity of LG secretory acini. MECs take part in the formation of extracellular matrix gland and participate in signal exchange between epithelium and stroma. MECs have a high level of plasticity and are able to differentiate into several cell lineages. Here, we provide a review on some of the MEC characteristics and their role in LG morphogenesis, maintenance, and repair.

  18. Reassessing the Roles of PIN Proteins and Anticlinal Microtubules during Pavement Cell Morphogenesis1[OPEN

    Science.gov (United States)

    Sawchuk, Megan G.; Scarpella, Enrico

    2018-01-01

    The leaf epidermis is a biomechanical shell that influences the size and shape of the organ. Its morphogenesis is a multiscale process in which nanometer-scale cytoskeletal protein complexes, individual cells, and groups of cells pattern growth and define macroscopic leaf traits. Interdigitated growth of neighboring cells is an evolutionarily conserved developmental strategy. Understanding how signaling pathways and cytoskeletal proteins pattern cell walls during this form of tissue morphogenesis is an important research challenge. The cellular and molecular control of a lobed cell morphology is currently thought to involve PIN-FORMED (PIN)-type plasma membrane efflux carriers that generate subcellular auxin gradients. Auxin gradients were proposed to function across cell boundaries to encode stable offset patterns of cortical microtubules and actin filaments between adjacent cells. Many models suggest that long-lived microtubules along the anticlinal cell wall generate local cell wall heterogeneities that restrict local growth and specify the timing and location of lobe formation. Here, we used Arabidopsis (Arabidopsis thaliana) reverse genetics and multivariate long-term time-lapse imaging to test current cell shape control models. We found that neither PIN proteins nor long-lived microtubules along the anticlinal wall predict the patterns of lobe formation. In fields of lobing cells, anticlinal microtubules are not correlated with cell shape and are unstable at the time scales of cell expansion. Our analyses indicate that anticlinal microtubules have multiple functions in pavement cells and that lobe initiation is likely controlled by complex interactions among cell geometry, cell wall stress patterns, and transient microtubule networks that span the anticlinal and periclinal walls. PMID:29192026

  19. Reassessing the Roles of PIN Proteins and Anticlinal Microtubules during Pavement Cell Morphogenesis.

    Science.gov (United States)

    Belteton, Samuel A; Sawchuk, Megan G; Donohoe, Bryon S; Scarpella, Enrico; Szymanski, Daniel B

    2018-01-01

    The leaf epidermis is a biomechanical shell that influences the size and shape of the organ. Its morphogenesis is a multiscale process in which nanometer-scale cytoskeletal protein complexes, individual cells, and groups of cells pattern growth and define macroscopic leaf traits. Interdigitated growth of neighboring cells is an evolutionarily conserved developmental strategy. Understanding how signaling pathways and cytoskeletal proteins pattern cell walls during this form of tissue morphogenesis is an important research challenge. The cellular and molecular control of a lobed cell morphology is currently thought to involve PIN-FORMED (PIN)-type plasma membrane efflux carriers that generate subcellular auxin gradients. Auxin gradients were proposed to function across cell boundaries to encode stable offset patterns of cortical microtubules and actin filaments between adjacent cells. Many models suggest that long-lived microtubules along the anticlinal cell wall generate local cell wall heterogeneities that restrict local growth and specify the timing and location of lobe formation. Here, we used Arabidopsis ( Arabidopsis thaliana ) reverse genetics and multivariate long-term time-lapse imaging to test current cell shape control models. We found that neither PIN proteins nor long-lived microtubules along the anticlinal wall predict the patterns of lobe formation. In fields of lobing cells, anticlinal microtubules are not correlated with cell shape and are unstable at the time scales of cell expansion. Our analyses indicate that anticlinal microtubules have multiple functions in pavement cells and that lobe initiation is likely controlled by complex interactions among cell geometry, cell wall stress patterns, and transient microtubule networks that span the anticlinal and periclinal walls. © 2018 American Society of Plant Biologists. All Rights Reserved.

  20. Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Shuxian Jiang

    2010-03-01

    Full Text Available Mammary stem cells are maintained within specific microenvironments and recruited throughout lifetime to reconstitute de novo the mammary gland. Mammary stem cells have been isolated through the identification of specific cell surface markers and in vivo transplantation into cleared mammary fat pads. Accumulating evidence showed that during the reformation of mammary stem cell niches by dispersed epithelial cells in the context of the intact epithelium-free mammary stroma, non-mammary epithelial cells may be sequestered and reprogrammed to perform mammary epithelial cell functions and to adopt mammary epithelial characteristics during reconstruction of mammary epithelium in regenerating mammary tissue in vivo.To examine whether other types of progenitor cells are able to contribute to mammary branching morphogenesis, we examined the potential of murine embryonic stem (mES cells, undergoing hematopoietic differentiation, to support mammary reconstitution in vivo. We observed that cells from day 14 embryoid bodies (EBs under hematopoietic differentiation condition, but not supernatants derived from these cells, when transplanted into denuded mammary fat pads, were able to contribute to both the luminal and myoepithelial lineages in branching ductal structures resembling the ductal-alveolar architecture of the mammary tree. No teratomas were observed when these cells were transplanted in vivo.Our data provide evidence for the dominance of the tissue-specific mammary stem cell niche and its role in directing mES cells, undergoing hematopoietic differentiation, to reprogram into mammary epithelial cells and to promote mammary epithelial morphogenesis. These studies should also provide insights into regeneration of damaged mammary gland and the role of the mammary microenvironment in reprogramming cell fate.

  1. Fungal Morphogenesis, from the Polarized Growth of Hyphae to Complex Reproduction and Infection Structures.

    Science.gov (United States)

    Riquelme, Meritxell; Aguirre, Jesús; Bartnicki-García, Salomon; Braus, Gerhard H; Feldbrügge, Michael; Fleig, Ursula; Hansberg, Wilhelm; Herrera-Estrella, Alfredo; Kämper, Jörg; Kück, Ulrich; Mouriño-Pérez, Rosa R; Takeshita, Norio; Fischer, Reinhard

    2018-06-01

    Filamentous fungi constitute a large group of eukaryotic microorganisms that grow by forming simple tube-like hyphae that are capable of differentiating into more-complex morphological structures and distinct cell types. Hyphae form filamentous networks by extending at their tips while branching in subapical regions. Rapid tip elongation requires massive membrane insertion and extension of the rigid chitin-containing cell wall. This process is sustained by a continuous flow of secretory vesicles that depends on the coordinated action of the microtubule and actin cytoskeletons and the corresponding motors and associated proteins. Vesicles transport cell wall-synthesizing enzymes and accumulate in a special structure, the Spitzenkörper, before traveling further and fusing with the tip membrane. The place of vesicle fusion and growth direction are enabled and defined by the position of the Spitzenkörper, the so-called cell end markers, and other proteins involved in the exocytic process. Also important for tip extension is membrane recycling by endocytosis via early endosomes, which function as multipurpose transport vehicles for mRNA, septins, ribosomes, and peroxisomes. Cell integrity, hyphal branching, and morphogenesis are all processes that are largely dependent on vesicle and cytoskeleton dynamics. When hyphae differentiate structures for asexual or sexual reproduction or to mediate interspecies interactions, the hyphal basic cellular machinery may be reprogrammed through the synthesis of new proteins and/or the modification of protein activity. Although some transcriptional networks involved in such reprogramming of hyphae are well studied in several model filamentous fungi, clear connections between these networks and known determinants of hyphal morphogenesis are yet to be established. Copyright © 2018 American Society for Microbiology.

  2. Moving domain computational fluid dynamics to interface with an embryonic model of cardiac morphogenesis.

    Directory of Open Access Journals (Sweden)

    Juhyun Lee

    Full Text Available Peristaltic contraction of the embryonic heart tube produces time- and spatial-varying wall shear stress (WSS and pressure gradients (∇P across the atrioventricular (AV canal. Zebrafish (Danio rerio are a genetically tractable system to investigate cardiac morphogenesis. The use of Tg(fli1a:EGFP (y1 transgenic embryos allowed for delineation and two-dimensional reconstruction of the endocardium. This time-varying wall motion was then prescribed in a two-dimensional moving domain computational fluid dynamics (CFD model, providing new insights into spatial and temporal variations in WSS and ∇P during cardiac development. The CFD simulations were validated with particle image velocimetry (PIV across the atrioventricular (AV canal, revealing an increase in both velocities and heart rates, but a decrease in the duration of atrial systole from early to later stages. At 20-30 hours post fertilization (hpf, simulation results revealed bidirectional WSS across the AV canal in the heart tube in response to peristaltic motion of the wall. At 40-50 hpf, the tube structure undergoes cardiac looping, accompanied by a nearly 3-fold increase in WSS magnitude. At 110-120 hpf, distinct AV valve, atrium, ventricle, and bulbus arteriosus form, accompanied by incremental increases in both WSS magnitude and ∇P, but a decrease in bi-directional flow. Laminar flow develops across the AV canal at 20-30 hpf, and persists at 110-120 hpf. Reynolds numbers at the AV canal increase from 0.07±0.03 at 20-30 hpf to 0.23±0.07 at 110-120 hpf (p< 0.05, n=6, whereas Womersley numbers remain relatively unchanged from 0.11 to 0.13. Our moving domain simulations highlights hemodynamic changes in relation to cardiac morphogenesis; thereby, providing a 2-D quantitative approach to complement imaging analysis.

  3. Reassessing the roles of PIN proteins and anticlinal microtubules during pavement cell morphogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Belteton, Samuel; Sawchuk, Megan G.; Donohoe, Bryon S.; Scarpella, Enrico; Szymanski, Daniel B.

    2017-11-30

    The leaf epidermis is a biomechanical shell that influences the size and shape of the organ. Its morphogenesis is a multiscale process in which nanometer-scale cytoskeletal protein complexes, individual cells, and groups of cells pattern growth and define macroscopic leaf traits. Interdigitated growth of neighboring cells is an evolutionarily conserved developmental strategy. Understanding how signaling pathways and cytoskeletal proteins pattern cell walls during this form of tissue morphogenesis is an important research challenge. The cellular and molecular control of a lobed cell morphology is currently thought to involve PIN-FORMED (PIN)-type plasma membrane efflux carriers that generate subcellular auxin gradients. Auxin gradients were proposed to function across cell boundaries to encode stable offset patterns of cortical microtubules and actin filaments between adjacent cells. Many models suggest that long-lived microtubules along the anticlinal cell wall generate local cell wall heterogeneities that restrict local growth and specify the timing and location of lobe formation. Here we used Arabidopsis reverse genetics and multivariate long-term time-lapse imaging to test current cell shape control models. We found that neither PIN proteins nor microtubules along the anticlinal wall predict the patterns of lobe formation. In fields of lobing cells, anticlinal microtubules are not correlated with cell shape and are unstable at the time scales of cell expansion. Our analyses indicate that anticlinal microtubules have multiple functions in pavement cells, and that lobe initiation is likely controlled by complex interactions among cell geometry, cell wall stress patterns, and transient microtubule networks that span the anticlinal and periclinal walls.

  4. Choriodecidual infection downregulates angiogenesis and morphogenesis pathways in fetal lungs from Macaca nemestrina.

    Directory of Open Access Journals (Sweden)

    Ryan M McAdams

    Full Text Available Intrauterine exposure to amniotic fluid (AF cytokines is thought to predispose to bronchopulmonary dysplasia (BPD. We evaluated the effects of GBS exposure on RNA expression in fetal lung tissue to determine early molecular pathways associated with fetal lung injury that may progress to BPD.Ten chronically catheterized pregnant monkeys (Macaca nemestrina at 118-125 days gestation (term = 172 days received choriodecidual inoculation of either: 1 Group B Streptococcus (n = 5 or 2 saline (n = 5. Cesarean section and fetal necropsy was performed in the first week after GBS or saline inoculation regardless of labor. RNA was extracted from fetal lungs and profiled by microarray. Results were analyzed using single gene, Gene Set, and Ingenuity Pathway Analysis. Validation was by RT-PCR and immunohistochemistry.Despite uterine quiescence in most cases, fetal lung injury occurred in four GBS cases (intra-alveolar neutrophils, interstitial thickening and one control (peri-mortem hemorrhage. Significant elevations of AF cytokines (TNF-α, IL-8, IL-1β, IL-6 were detected in GBS versus controls (p<0.05. Lung injury was not directly caused by GBS, because GBS was undetectable by culture and PCR in the AF and fetal lungs. A total of 335 genes were differentially expressed greater than 1.5 fold (p<0.05 with GBS exposure associated with a striking upregulation of genes in innate and adaptive immunity and downregulation of pathways for angiogenesis, morphogenesis, and cellular growth and development.A transient choriodecidual infection may induce fetal lung injury with profound alterations in the genetic program of the fetal lung before signs of preterm labor. Our results provide a window for the first time into early molecular pathways disrupting fetal lung angiogenesis and morphogenesis before preterm labor occurs, which may set the stage for BPD. A strategy to prevent BPD should target the fetus in utero to attenuate alterations in the fetal lung

  5. Study on the abnormal morphogenesis of the arterial end of the heart induced by neutron irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Hidaka, N [Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology

    1980-02-01

    Transposition complexes of the great arteries were frequently produced in rat embryonic hearts whose mothers were exposed to a single whole-body dose of 130 rad 14.1 MeV fast neutron radiation on 8 day after conception. To clarify the morphogenesis of transposition complexes, especially double outlet right ventricle (DORV), embryonic rat hearts were serially sectioned and were reconstructed photographically 13 to 16 days after conception, when truncal swelling, intercalated valve swelling, and conical ridges appeared. In the control group, all the hearts had a normal D (dextral) loop. In the experimental group, 82.6% of the hearts had a D loop, 11.3% had an L (levo) loop, and 5.9% had an A (anterior) loop. In this group, the D loop hearts were divided into normal, retarded, and abnormal. Most of the retarded hearts developed into abnormal hearts. The positional relationships between experimentally produced swelling and ridges are classified. Morphologic anomalies are formed in the truncoconal region and correspond to the site of and the quantitative changes of the swelling and ridges. Abnormality in the position and extent of the swelling and ridges is the most important characteristic in the morphogenesis of transposition complexes. The second most important characteristic is abnormality in the time of appearance and the extent and site of cell death in the conical septum. DORV is embryologically divided into two types: a type in which the great arteries are normally related and a type in which they are inversely related. The developmental process of the DORV is entirely different from that of the complete transposition of the great arteries.

  6. Macroalgal Morphogenesis Induced by Waterborne Compounds and Bacteria in Coastal Seawater.

    Directory of Open Access Journals (Sweden)

    Jan Grueneberg

    Full Text Available Axenic gametes of the marine green macroalga Ulva mutabilis Føyn (Ria Formosa, locus typicus exhibit abnormal development into slow-growing callus-like colonies with aberrant cell walls. Under laboratory conditions, it was previously demonstrated that all defects in growth and thallus development can be completely abolished when axenic gametes are inoculated with a combination of two specific bacterial strains originally identified as Roseobacter sp. strain MS2 and Cytophaga sp. strain MS6. These bacteria release diffusible morphogenetic compounds (= morphogens, which act similar to cytokinin and auxin. To investigate the ecological relevance of the waterborne bacterial morphogens, seawater samples were collected in the Ria Formosa lagoon (Algarve, Southern Portugal at 20 sampling sites and tidal pools to assess their morphogenetic effects on the axenic gametes of U. mutabilis. Specifically the survey revealed that sterile-filtered seawater samples can completely recover growth and morphogenesis of U. mutabilis under axenic conditions. Morphogenetic activities of free-living and epiphytic bacteria isolated from the locally very abundant Ulva species (i.e., U. rigida were screened using a multiwell-based testing system. The most represented genera isolated from U. rigida were Alteromonas, Pseudoalteromonas and Sulfitobacter followed by Psychrobacter and Polaribacter. Several naturally occurring bacterial species could emulate MS2 activity (= induction of cell divisions regardless of taxonomic affiliation, whereas the MS6 activity (= induction of cell differentiation and cell wall formation was species-specific and is probably a feature of difficult-to-culture bacteria. Interestingly, isolated bacteroidetes such as Algoriphagus sp. and Polaribacter sp. could individually trigger complete Ulva morphogenesis and thus provide a novel mode of action for bacterial-induced algal development. This study also highlights that the accumulation of algal

  7. Eye and heart morphogenesis are dependent on melatonin signaling in chick embryos.

    Science.gov (United States)

    Nogueira, Renato C; Sampaio, Lucia de Fatima S

    2017-10-15

    Calmodulin is vital for chick embryos morphogenesis in the incubation time 48-66 h when the rudimentary C-shaped heart attains an S-shaped pattern and the optic vesicles develop into optic cups. Melatonin is in the extraembryonic yolk sac of the avian egg; melatonin binds calmodulin. The aim of this study was to investigate the function of melatonin in the formation of the chick embryo optic cups and S-shaped heart, by pharmacological methods and immunoassays. Mel1a melatonin receptor immunofluorescence was distributed in the optic cups and rudimentary hearts. We separated embryonated chicken eggs at 48 h of incubation into basal, control and drug-treated groups, with treatment applied in the egg air sac. At 66 h of incubation, embryos were excised from the eggs and analyzed. Embryos from the basal, control (distilled water), melatonin and 6-chloromelatonin (melatonin receptor agonist) groups had regular optic cups and an S-shaped heart, while those from the calmidazolium (calmodulin inhibitor) group did not. Embryos from the luzindole (melatonin receptor antagonist) and prazosin (Mel1c melatonin receptor antagonist) groups did not have regular optic cups. Embryos from the 4-P-PDOT (Mel1b melatonin receptor antagonist) group did not have an S-shaped heart. Previous application of the melatonin, 6-chloromelatonin or forskolin (adenylate cyclase enhancer) prevented the abnormal appearance of chick embryos from the calmidazolium, luzindole, prazosin and 4-P-PDOT groups. However, 6-chloromelatonin and forskolin only partially prevented the development of defective eye cups in embryos from the calmidazolium group. The results suggested that melatonin modulates chick embryo morphogenesis via calmodulin and membrane receptors. © 2017. Published by The Company of Biologists Ltd.

  8. Human lung fibroblast-derived matrix facilitates vascular morphogenesis in 3D environment and enhances skin wound healing.

    Science.gov (United States)

    Du, Ping; Suhaeri, Muhammad; Ha, Sang Su; Oh, Seung Ja; Kim, Sang-Heon; Park, Kwideok

    2017-05-01

    Extracellular matrix (ECM) is crucial to many aspects of vascular morphogenesis and maintenance of vasculature function. Currently the recapitulation of angiogenic ECM microenvironment is still challenging, due mainly to its diverse components and complex organization. Here we investigate the angiogenic potential of human lung fibroblast-derived matrix (hFDM) in creating a three-dimensional (3D) vascular construct. hFDM was obtained via decellularization of in vitro cultured human lung fibroblasts and analyzed via immunofluorescence staining and ELISA, which detect multiple ECM macromolecules and angiogenic growth factors (GFs). Human umbilical vein endothelial cells (HUVECs) morphology was more elongated and better proliferative on hFDM than on gelatin-coated substrate. To prepare 3D construct, hFDM is collected, quantitatively analyzed, and incorporated in collagen hydrogel (Col) with HUVECs. Capillary-like structure (CLS) formation at 7day was significantly better with the groups containing higher doses of hFDM compared to the Col group (control). Moreover, the group (Col/hFDM/GFs) with both hFDM and angiogenic GFs (VEGF, bFGF, SDF-1) showed the synergistic activity on CLS formation and found much larger capillary lumen diameters with time. Further analysis of hFDM via angiogenesis antibody array kit reveals abundant biochemical cues, such as angiogenesis-related cytokines, GFs, and proteolytic enzymes. Significantly up-regulated expression of VE-cadherin and ECM-specific integrin subunits was also noticed in Col/hFDM/GFs. In addition, transplantation of Col/hFMD/GFs with HUVECs in skin wound model presents more effective re-epithelialization, many regenerated hair follicles, better transplanted cells viability, and advanced neovascularization. We believe that current system is a very promising platform for 3D vasculature construction in vitro and for cell delivery toward therapeutic applications in vivo. Functional 3D vasculature construction in vitro is still

  9. Targeted Expression of Stromelysin-1 in Mammary Gland Provides Evidence for a Role of Proteinases in Branching Morphogenesis and the Requirement for an Intact Basement Membrane for Tissue-specific Gene Expression

    Energy Technology Data Exchange (ETDEWEB)

    Sympson, Carolyn J; Talhouk, Rabih S; Alexander, Caroline M; Chin, Jennie R; Cliff, Shirley M; Bissell, Mina J; Werb, Zena

    1994-05-01

    The extracellular matrix (ECM) is an important regulator of the differentiated phenotype of mammary epithelial cells in culture. Despite the fact that ECM-degrading enzymes have been implicated in morphogenesis and tissue remodeling, there is little evidence for a direct role for such regulation in vivo. We generated transgenic mice that express autoactivated isoforms of the matrix metalloproteinase stromelysin-1, under the control of the whey acidic protein gene promoter, to examine the effect of inappropriate expression of this enzyme. Stromelysin-1 is implicated as the primary player in the loss of basement membrane and loss of function in the mammary gland during involution. The transgene was expressed at low levels in mammary glands of virgin female mice, leading to an unexpected phenotype: The primary ducts had supernumerary branches and showed precocious development of alveoli that expressed beta-casein at levels similar to that of an early- to mid-pregnant gland. Lactating glands showed high levels of transgene expression, with accumulation at the basement membrane, and a decrease in laminin and collagen IV, resulting in a loss of basement membrane integrity; this was accompanied by a dramatic alteration of alveolar morphology, with decreased size and shrunken lumina containing little beta-casein. During pregnancy, expression of endogenous whey acidic protein and beta-casein was reduced in transgenic glands, confirming the observed dependence of milk protein transcription of ECM in mammary epithelial cells in culture. These data provide direct evidence that stromelysin-1 activity can be morphogenic for mammary epithelial cells, inducing hyperproliferation and differentiation in virgin animals, and that its lytic activity can, indeed, disrupt membrane integrity and reduce mammary-specific function. We conclude that the balance of ECM-degrading enzymes with their inhibitors, and the associated regulation of ECM structure, is crucial for tissue-specific gene

  10. Combination of Hypomorphic Mutations of the Drosophila Homologues of Aryl Hydrocarbon Receptor and Nucleosome Assembly Protein Family Genes Disrupts Morphogenesis, Memory and Detoxification

    OpenAIRE

    Kuzin, Boris A.; Nikitina, Ekaterina A.; Cherezov, Roman O.; Vorontsova, Julia E.; Slezinger, Mikhail S.; Zatsepina, Olga G.; Simonova, Olga B.; Enikolopov, Grigori N.; Savvateeva-Popova, Elena V.

    2014-01-01

    Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response...

  11. Dynamics of cell polarity in tissue morphogenesis: a comparative view from Drosophila and Ciona [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Michael T. Veeman

    2016-06-01

    Full Text Available Tissues in developing embryos exhibit complex and dynamic rearrangements that shape forming organs, limbs, and body axes. Directed migration, mediolateral intercalation, lumen formation, and other rearrangements influence the topology and topography of developing tissues. These collective cell behaviors are distinct phenomena but all involve the fine-grained control of cell polarity. Here we review recent findings in the dynamics of polarized cell behavior in both the Drosophila ovarian border cells and the Ciona notochord. These studies reveal the remarkable reorganization of cell polarity during organ formation and underscore conserved mechanisms of developmental cell polarity including the Par/atypical protein kinase C (aPKC and planar cell polarity pathways. These two very different model systems demonstrate important commonalities but also key differences in how cell polarity is controlled in tissue morphogenesis. Together, these systems raise important, broader questions on how the developmental control of cell polarity contributes to morphogenesis of diverse tissues across the metazoa.

  12. Towards an automated analysis of video-microscopy images of fungal morphogenesis

    Directory of Open Access Journals (Sweden)

    Diéguez-Uribeondo, Javier

    2005-06-01

    Full Text Available Fungal morphogenesis is an exciting field of cell biology and several mathematical models have been developed to describe it. These models require experimental evidences to be corroborated and, therefore, there is a continuous search for new microscopy and image analysis techniques. In this work, we have used a Canny-edge-detector based technique to automate the generation of hyphal profiles and calculation of morphogenetic parameters such as diameter, elongation rates and hyphoid fitness. The results show that the data obtained with this technique are similar to published data generated with manualbased tracing techniques and that have been carried out on the same species or genus. Thus, we show that application of edge detector-based technique to hyphal growth represents an efficient and accurate method to study hyphal morphogenesis. This represents the first step towards an automated analysis of videomicroscopy images of fungal morphogenesis.La morfogénesis de los hongos es un área de estudio de gran relevancia en la biología celular y en la que se han desarrollado varios modelos matemáticos. Los modelos matemáticos de procesos biológicos precisan de pruebas experimentales que apoyen y corroboren las predicciones teóricas y, por este motivo, existe una búsqueda continua de nuevas técnicas de microscopía y análisis de imágenes para su aplicación en el estudio del crecimiento celular. En este trabajo hemos utilizado una técnica basada en un detector de contornos llamado “Canny-edge-detectorâ€� con el objetivo de automatizar la generación de perfiles de hifas y el cálculo de parámetros morfogenéticos, tales como: el diámetro, la velocidad de elongación y el ajuste con el perfil hifoide, es decir, el perfil teórico de las hifas de los hongos. Los resultados obtenidos son similares a los datos publicados a partir de técnicas manuales de trazado de contornos, generados en la misma especie y género. De esta manera

  13. Hanging on for the ride: adhesion to the extracellular matrix mediates cellular responses in skeletal muscle morphogenesis and disease.

    Science.gov (United States)

    Goody, Michelle F; Sher, Roger B; Henry, Clarissa A

    2015-05-01

    Skeletal muscle specification and morphogenesis during early development are critical for normal physiology. In addition to mediating locomotion, skeletal muscle is a secretory organ that contributes to metabolic homeostasis. Muscle is a highly adaptable tissue, as evidenced by the ability to increase muscle cell size and/or number in response to weight bearing exercise. Conversely, muscle wasting can occur during aging (sarcopenia), cancer (cancer cachexia), extended hospital stays (disuse atrophy), and in many genetic diseases collectively known as the muscular dystrophies and myopathies. It is therefore of great interest to understand the cellular and molecular mechanisms that mediate skeletal muscle development and adaptation. Muscle morphogenesis transforms short muscle precursor cells into long, multinucleate myotubes that anchor to tendons via the myotendinous junction. This process requires carefully orchestrated interactions between cells and their extracellular matrix microenvironment. These interactions are dynamic, allowing muscle cells to sense biophysical, structural, organizational, and/or signaling changes within their microenvironment and respond appropriately. In many musculoskeletal diseases, these cell adhesion interactions are disrupted to such a degree that normal cellular adaptive responses are not sufficient to compensate for accumulating damage. Thus, one major focus of current research is to identify the cell adhesion mechanisms that drive muscle morphogenesis, with the hope that understanding how muscle cell adhesion promotes the intrinsic adaptability of muscle tissue during development may provide insight into potential therapeutic approaches for muscle diseases. Our objectives in this review are to highlight recent studies suggesting conserved roles for cell-extracellular matrix adhesion in vertebrate muscle morphogenesis and cellular adaptive responses in animal models of muscle diseases. Copyright © 2015 Elsevier Inc. All rights

  14. Protein-Trap Insertional Mutagenesis Uncovers New Genes Involved in Zebrafish Skin Development, Including a Neuregulin 2a-Based ErbB Signaling Pathway Required during Median Fin Fold Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Stephanie E Westcot

    Full Text Available Skin disorders are widespread, but available treatments are limited. A more comprehensive understanding of skin development mechanisms will drive identification of new treatment targets and modalities. Here we report the Zebrafish Integument Project (ZIP, an expression-driven platform for identifying new skin genes and phenotypes in the vertebrate model Danio rerio (zebrafish. In vivo selection for skin-specific expression of gene-break transposon (GBT mutant lines identified eleven new, revertible GBT alleles of genes involved in skin development. Eight genes--fras1, grip1, hmcn1, msxc, col4a4, ahnak, capn12, and nrg2a--had been described in an integumentary context to varying degrees, while arhgef25b, fkbp10b, and megf6a emerged as novel skin genes. Embryos homozygous for a GBT insertion within neuregulin 2a (nrg2a revealed a novel requirement for a Neuregulin 2a (Nrg2a-ErbB2/3-AKT signaling pathway governing the apicobasal organization of a subset of epidermal cells during median fin fold (MFF morphogenesis. In nrg2a mutant larvae, the basal keratinocytes within the apical MFF, known as ridge cells, displayed reduced pAKT levels as well as reduced apical domains and exaggerated basolateral domains. Those defects compromised proper ridge cell elongation into a flattened epithelial morphology, resulting in thickened MFF edges. Pharmacological inhibition verified that Nrg2a signals through the ErbB receptor tyrosine kinase network. Moreover, knockdown of the epithelial polarity regulator and tumor suppressor lgl2 ameliorated the nrg2a mutant phenotype. Identifying Lgl2 as an antagonist of Nrg2a-ErbB signaling revealed a significantly earlier role for Lgl2 during epidermal morphogenesis than has been described to date. Furthermore, our findings demonstrated that successive, coordinated ridge cell shape changes drive apical MFF development, making MFF ridge cells a valuable model for investigating how the coordinated regulation of cell polarity

  15. Protein-Trap Insertional Mutagenesis Uncovers New Genes Involved in Zebrafish Skin Development, Including a Neuregulin 2a-Based ErbB Signaling Pathway Required during Median Fin Fold Morphogenesis.

    Science.gov (United States)

    Westcot, Stephanie E; Hatzold, Julia; Urban, Mark D; Richetti, Stefânia K; Skuster, Kimberly J; Harm, Rhianna M; Lopez Cervera, Roberto; Umemoto, Noriko; McNulty, Melissa S; Clark, Karl J; Hammerschmidt, Matthias; Ekker, Stephen C

    2015-01-01

    Skin disorders are widespread, but available treatments are limited. A more comprehensive understanding of skin development mechanisms will drive identification of new treatment targets and modalities. Here we report the Zebrafish Integument Project (ZIP), an expression-driven platform for identifying new skin genes and phenotypes in the vertebrate model Danio rerio (zebrafish). In vivo selection for skin-specific expression of gene-break transposon (GBT) mutant lines identified eleven new, revertible GBT alleles of genes involved in skin development. Eight genes--fras1, grip1, hmcn1, msxc, col4a4, ahnak, capn12, and nrg2a--had been described in an integumentary context to varying degrees, while arhgef25b, fkbp10b, and megf6a emerged as novel skin genes. Embryos homozygous for a GBT insertion within neuregulin 2a (nrg2a) revealed a novel requirement for a Neuregulin 2a (Nrg2a)-ErbB2/3-AKT signaling pathway governing the apicobasal organization of a subset of epidermal cells during median fin fold (MFF) morphogenesis. In nrg2a mutant larvae, the basal keratinocytes within the apical MFF, known as ridge cells, displayed reduced pAKT levels as well as reduced apical domains and exaggerated basolateral domains. Those defects compromised proper ridge cell elongation into a flattened epithelial morphology, resulting in thickened MFF edges. Pharmacological inhibition verified that Nrg2a signals through the ErbB receptor tyrosine kinase network. Moreover, knockdown of the epithelial polarity regulator and tumor suppressor lgl2 ameliorated the nrg2a mutant phenotype. Identifying Lgl2 as an antagonist of Nrg2a-ErbB signaling revealed a significantly earlier role for Lgl2 during epidermal morphogenesis than has been described to date. Furthermore, our findings demonstrated that successive, coordinated ridge cell shape changes drive apical MFF development, making MFF ridge cells a valuable model for investigating how the coordinated regulation of cell polarity and cell shape

  16. Microgravity simulation activates Cdc42 via Rap1GDS1 to promote vascular branch morphogenesis during vasculogenesis

    Directory of Open Access Journals (Sweden)

    Shouli Wang

    2017-12-01

    Full Text Available Gravity plays an important role in normal tissue maintenance. The ability of stem cells to repair tissue loss in space through regeneration and differentiation remains largely unknown. To investigate the impact of microgravity on blood vessel formation from pluripotent stem cells, we employed the embryoid body (EB model for vasculogenesis and simulated microgravity by clinorotation. We first differentiated mouse embryonic stem cells into cystic EBs containing two germ layers and then analyzed vessel formation under clinorotation. We observed that endothelial cell differentiation was slightly reduced under clinorotation, whereas vascular branch morphogenesis was markedly enhanced. EB-derived endothelial cells migrated faster, displayed multiple cellular processes, and had higher Cdc42 and Rac1 activity when subjected to clinorotation. Genetic analysis and rescue experiments demonstrated that Cdc42 but not Rac1 is required for microgravity-induced vascular branch morphogenesis. Furthermore, affinity pull-down assay and mass spectrometry identified Rap1GDS1 to be a Cdc42 guanine nucleotide exchange factor, which was upregulated by clinorotation. shRNA-mediated knockdown of Rap1GDS1 selectively suppressed Cdc42 activation and inhibited both baseline and microgravity-induced vasculogenesis. This was rescued by ectopic expression of constitutively active Cdc42. Taken together, these results support the notion that simulated microgravity activates Cdc42 via Rap1GDS1 to promote vascular branch morphogenesis.

  17. Characterization and role of p53 family members in the symbiont-induced morphogenesis of the Euprymna scolopes light organ.

    Science.gov (United States)

    Goodson, Michael S; Crookes-Goodson, Wendy J; Kimbell, Jennifer R; McFall-Ngai, Margaret J

    2006-08-01

    Within hours of hatching, the squid Euprymna scolopes forms a specific light organ symbiosis with the marine luminous bacterium Vibrio fischeri. Interactions with the symbiont result in the loss of a complex ciliated epithelium dedicated to promoting colonization of host tissue, and some or all of this loss is due to widespread, symbiont-induced apoptosis. Members of the p53 family, including p53, p63, and p73, are conserved across broad phyletic lines and p63 is thought to be the ancestral gene. These proteins have been shown to induce apoptosis and developmental morphogenesis. In this study, we characterized p63-like transcripts from mRNA isolated from the symbiotic tissues of E. scolopes and described their role in symbiont-induced morphogenesis. Using degenerate RT-PCR and RACE PCR, we identified two p63-like transcripts encoding proteins of 431 and 567 amino acids. These transcripts shared identical nucleotides where they overlapped, suggesting that they are splice variants of the same gene. Immunocytochemistry and Western blots using an antibody specific for E. scolopes suggested that the p53 family members are activated in cells of the symbiont-harvesting structures of the symbiotic light organ. We propose that once the symbiosis is initiated, a symbiont-induced signal activates p53 family members, inducing apoptosis and developmental morphogenesis of the light organ.

  18. Homology with vesicle fusion mediator syntaxin-1a predicts determinants ofepimorphin/syntaxin-2 function in mammary epithelial morphogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Connie S.; Nelson, Celeste M.; Khauv, Davitte; Bennett, Simone; Radisky, Evette S.; Hirai, Yohei; Bissell, Mina J.; Radisky, Derek C.

    2009-06-03

    We have shown that branching morphogenesis of mammary ductal structures requires the action of the morphogen epimorphin/syntaxin-2. Epimorphin, originally identified as an extracellular molecule, is identical to syntaxin-2, an intracellular molecule that is a member of the extensively investigated syntaxin family of proteins that mediate vesicle trafficking. We show here that although epimorphin/syntaxin-2 is highly homologous to syntaxin-1a, only epimorphin/syntaxin-2 can stimulate mammary branching morphogenesis. We construct a homology model of epimorphin/syntaxin-2 based on the published structure of syntaxin-1a, and we use this model to identify the structural motif responsible for the morphogenic activity. We identify four residues located within the cleft between helices B and C that differ between syntaxin-1a and epimorphin/syntaxin-2; through site-directed mutagenesis of these four amino acids, we confer the properties of epimorphin for cell adhesion, gene activation, and branching morphogenesis onto the inactive syntaxin-1a template. These results provide a dramatic demonstration of the use of structural information about one molecule to define a functional motif of a second molecule that is related at the sequence level but highly divergent functionally.

  19. Growth and morphogenesis of embryonic mouse organs on non-coated and extracellular matrix-coated Biopore membrane

    Science.gov (United States)

    Hardman, P.; Klement, B. J.; Spooner, B. S.

    1993-01-01

    Embryonic mouse salivary glands, pancreata, and kidneys were isolated from embryos of appropriate gestational age by microdissection, and were cultured on Biopore membrane either non-coated or coated with type I collagen or Matrigel. As expected, use of Biopore membrane allowed high quality photomicroscopy of the living organs. In all organs extensive mesenchymal spreading was observed in the presence of type I collagen or Matrigel. However, differences were noted in the effects of extracellular matrix (ECM) coatings on epithelial growth and morphogenesis: salivary glands were minimally affected, pancreas morphogenesis was adversely affected, and kidney growth and branching apparently was enhanced. It is suggested that these differences in behaviour reflect differences in the strength of interactions between the mesenchymal cells and their surrounding endogenous matrix, compared to the exogenous ECM macromolecules. This method will be useful for culture of these and other embryonic organs. In particular, culture of kidney rudiments on ECM-coated Biopore offers a great improvement over previously used methods which do not allow morphogenesis to be followed in vitro.

  20. A study of morphogenesis of digital malformation on rat embryo by x-irradiation

    International Nuclear Information System (INIS)

    Kim, Jhai Dhuck; You, Dong Soo

    1981-01-01

    The author studied in the effects of x-irradiation to the development of digital malformation in gestation rats. The time-matings occurred between 6 p.m. and 8 a.m. and females with copulation plugs at 8 a.m. were isolated and properly marked for evidence of copulation. The lower abdomen of mothers were exposed to x-irradiation on the 11 1/2th day of gestation, the critical period developing digital malformation, respectively 100, 150, 200, 250, 300 and 350 rads. At 18 1/2th day of post-conception total 50 pregnant females were dissected and the incidence of digital malformations were obtained. Rat embryos on the 12, 13, 14, 15, 16th day of gestation irradiated by 250 rads were examined for morphogenesis of digital malformation. Digital radiating lines were examined in water and histologically by H-E stain. Supra vital stain samples by Nile-blue sulfate in 37 .deg. C normal saline were prepared for the observation of cell necrosis regions and morphogenesis of digits. The results obtained were as follows; 1. By x-irradiation on 11th day of gestation, digital malformations of Ectrodactylia, Syndactylia, Polydactylia and Hematodactylia were developed. Ectrodactylia showed the effective relationship to the amount of irradiation, however Syndactylia and Poydactylia did not. 2. By x-irradiation, cell necrosis of digital germ was appeared markedly, but in 48 hours after irradiation was depressed to the periphery of digital germ and in 72 hours after irradiation was disappeared. Digital radiating line showed marked state of malformation in 48 hours after irradiation and continued to show the same amount of physiological cell necrosis as the compared control group in 72 hours after irradiation. But in the Syndactylia, physiological cell necrosis was not able to be recognized. 3. Ectrodactylia induced by x-irradiation was considered as the direct result of cell necrosis of digital origin, however, Polydactylia and Syndactylia were considered as the result of some effect in

  1. Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane

    Energy Technology Data Exchange (ETDEWEB)

    BARCELLOS-HOFF, M. H; AGGELER, J.; RAM, T. G; BISSELL, M. J

    1989-02-01

    An essential feature of mammary gland differentiation during pregnancy is the formation of alveoli composed of polarized epithelial cells, which, under the influence of lactogenic hormones, secrete vectorially and sequester milk proteins. Previous culture studies have described either organization of cells polarized towards lumina containing little or no demonstrable tissue-specific protein, or establishment of functional secretory cells exhibiting little or no glandular architecture. In this paper, we report that tissue-specific vectorial secretion coincides with the formation of functional alveoli-like structures by primary mammary epithelial cells cultured on a reconstituted basement membrane matrix (derived from Engelbreth-Holm-Swarm murine tumour). Morphogenesis of these unique three-dimensional structures was initiated by cell-directed remodelling of the exogenous matrix leading to reorganization of cells into matrixensheathed aggregates by 24 h after plating. The aggregates subsequently cavitated, so that by day 6 the cells were organized into hollow spheres in which apical cell surfaces faced lumina sealed by tight junctions and basal surfaces were surrounded by a distinct basal lamina. The profiles of proteins secreted into the apical (luminal) and basal (medium) compartments indicated that these alveoli-like structures were capable of an appreciable amount of vectorial secretion. Immunoprecipitation with a broad spectrum milk antiserum showed that more than 80% of caseins were secreted into the lumina, whereas iron-binding proteins (both lactoferrin and transferrin) were present in comparable amounts in each compartment. Thus, these mammary cells established protein targeting pathways directing milk-specific proteins to the luminal compartment. A time course monitoring secretory activity demonstrated that establishment of tissue-specific vectorial secretion and increased total and milk protein secretion coincided with functional alveolar

  2. Electromagnetic Resonance in Biological Form: A Role for Fields in Morphogenesis

    International Nuclear Information System (INIS)

    Pietak, Alexis M

    2011-01-01

    In morphogenesis, the mechanisms through which homogeneous, symmetric collectives of self-same cells are able to consistently and precisely establish long-range pattern remain an open question of scientific research. This work explores the hypothesis of developing biological structures as dielectric microwave resonators, using plant leaves as a working example. A finite element analysis (FEA) model was designed to determine if suitable resonant modes were physically possible for geometric and electrical parameters similar to those of developing leaf tissue. Using the FEA model, resonant EM modes with patterns of relevance to developing leaf vein modalities were detected. Here I show how the single physical mechanism of EM resonance can self-consistently account for different kinds of key symmetry-breaking operations characteristic of a variety of leaf vascular patterns. On account of the existence of shared geometric signatures in a leaf's vascular pattern and the electric field component of EM resonant modes supported by a leaf-like structure, further theoretical and experimental investigations are warranted. Significantly, this hypothesis is not limited to leaf vascular patterning, but may be applicable to a variety of morphogenetic phenomena in a number of living systems.

  3. Dynamics, morphogenesis and convergence of evolutionary quantum Prisoner's Dilemma games on networks

    Science.gov (United States)

    Yong, Xi

    2016-01-01

    The authors proposed a quantum Prisoner's Dilemma (PD) game as a natural extension of the classic PD game to resolve the dilemma. Here, we establish a new Nash equilibrium principle of the game, propose the notion of convergence and discover the convergence and phase-transition phenomena of the evolutionary games on networks. We investigate the many-body extension of the game or evolutionary games in networks. For homogeneous networks, we show that entanglement guarantees a quick convergence of super cooperation, that there is a phase transition from the convergence of defection to the convergence of super cooperation, and that the threshold for the phase transitions is principally determined by the Nash equilibrium principle of the game, with an accompanying perturbation by the variations of structures of networks. For heterogeneous networks, we show that the equilibrium frequencies of super-cooperators are divergent, that entanglement guarantees emergence of super-cooperation and that there is a phase transition of the emergence with the threshold determined by the Nash equilibrium principle, accompanied by a perturbation by the variations of structures of networks. Our results explore systematically, for the first time, the dynamics, morphogenesis and convergence of evolutionary games in interacting and competing systems. PMID:27118882

  4. HNK-1 immunoreactivity during early morphogenesis of the head region in a nonmodel vertebrate, crocodile embryo

    Science.gov (United States)

    Kundrát, Martin

    2008-11-01

    The present study examines HNK-1 immunoidentification of a population of the neural crest (NC) during early head morphogenesis in the nonmodel vertebrate, the crocodile ( Crocodylus niloticus) embryos. Although HNK-1 is not an exclusive NC marker among vertebrates, temporospatial immunoreactive patterns found in the crocodile are almost consistent with NC patterns derived from gene expression studies known in birds (the closest living relatives of crocodiles) and mammals. In contrast to birds, the HNK-1 epitope is immunoreactive in NC cells at the neural fold level in crocodile embryos and therefore provides sufficient base to assess early migratory events of the cephalic NC. I found that crocodile NC forms three classic migratory pathways in the head: mandibular, hyoid, and branchial. Further, I demonstrate that, besides this classic phenotype, there is also a forebrain-derived migratory population, which consolidates into a premandibular stream in the crocodile. In contrast to the closely related chick model, crocodilian premandibular and mandibular NC cells arise from the open neural tube suggesting that species-specific heterochronic behavior of NC may be involved in the formation of different vertebrate facial phenotypes.

  5. Localization and cloning of the gene(s) of bacteriophage PM2 responsible for membrane morphogenesis

    International Nuclear Information System (INIS)

    Armour, G.A.

    1988-01-01

    Proteins implicated in membrane morphogenesis (sp6.6 and sp13) have been previously identified by analysis of membrane proteins in the membrane of the purified phage. Analysis of a ts viral mutant that produces empty membrane vesicles also indicated the unique presence of viral structural protein sp6.6. In this work the gene for sp6.6 was localized on the PM2 genome by in vitro coupled transcription-translation directed by restriction endonuclease fragments of PM2 DNA. A Hind III fragment containing the sp6.6 gene among others was cloned into pBR322 in E. coli. Examination with the electron microscope revealed the production of new membrane vesicles whose size were similar to that of the natural membrane of PM2. Clones were then constructed in the pUC family of plasmids which uses the Lac promoter and pPL-lambda which uses the promoter left of lambda. pUC clones were unable to produce vesicles or detectable sp6.6. A pPL-lambda clone was produced 3.5 Kbp in size, that produced p6.6 as detected by SDS-PAGE of radiolabeled protein and immunoblotting

  6. Flask sealing on in vitro seed germination and morphogenesis of two types of ornamental pepper explants

    Directory of Open Access Journals (Sweden)

    Diego Silva Batista

    Full Text Available ABSTRACT: The influence of flask sealing and explant source on the in vitro morphogenesis of pepper, were evaluated in Capsicum annuum. Seeds were sterilized and inoculated in Murashige and Skoog media supplemented with vitamins, myo-inositol, sucrose, and agar. Gas exchange was evaluated in the germination stage by comparing 3 flask-sealing systems: rigid polypropylene lids (PLs without vents, PLs with 1 vent, and PLs with 2 vents covered with membranes. In the regeneration stage, cotyledon and hypocotyl segments were transferred to the organogenesis-inducing media, being the different sealing types also tested in a factorial scheme. Photosynthetic pigments, morphological and hystological analyses were conducted for each treatment. Plants maintained in glass flasks capped with vented lids showed more vigorous growth and differentiated anatomical structures. These treatments resulted in taller plants, higher numbers and more expanded leaves, higher fresh and dry weights, and an increase in photosynthetic pigments. Cultivation of C. annuum in flasks with reduced gas exchange was more effective on callus induction. During the regeneration stage, hypocotyls were more effective than cotyledons. Sealing type influenced the morphogenic responses of pepper, demonstrating that an increase in gas exchange has a positive effect on biomass production and acclimatization of the plantlets.

  7. Transcript profiling of Wilms tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia.

    Science.gov (United States)

    Li, Wenliang; Kessler, Patricia; Williams, Bryan R G

    2005-01-13

    Anaplasia (unfavorable histology) is associated with therapy resistance and poor prognosis of Wilms tumor, but the molecular basis for this phenotype is unclear. Here, we used a cDNA array with 9240 clones relevant to cancer biology and/or kidney development to examine the expression profiles of 54 Wilms tumors, five normal kidneys and fetal kidney. By linking genes differentially expressed between fetal kidney and Wilms tumors to kidney morphogenesis, we found that genes expressed at a higher level in Wilms tumors tend to be expressed more in uninduced metanephrogenic mesenchyme or blastema than in their differentiated structures. Conversely, genes expressed at a lower level in Wilms tumors tend to be expressed less in uninduced metanephrogenic mesenchyme or blastema. We also identified 97 clones representing 76 Unigenes or unclustered ESTs that clearly separate anaplastic Wilms tumors from tumors with favorable histology. Genes in this set provide insight into the nature of the abnormal nuclear morphology of anaplastic tumors and may facilitate identification of molecular targets to improve their responsiveness to treatment.

  8. Nordihydroguaiaretic acid (NDGA) inhibits replication and viral morphogenesis of dengue virus.

    Science.gov (United States)

    Soto-Acosta, Rubén; Bautista-Carbajal, Patricia; Syed, Gulam H; Siddiqui, Aleem; Del Angel, Rosa M

    2014-09-01

    Dengue is the most common mosquito borne viral disease in humans. The infection with any of the 4 dengue virus serotypes (DENV) can either be asymptomatic or manifest in two clinical forms, the mild dengue fever or the more severe dengue hemorrhagic fever that may progress into dengue shock syndrome. A DENV replicative cycle relies on host lipid metabolism; specifically, DENV infection modulates cholesterol and fatty acid synthesis, generating a lipid-enriched cellular environment necessary for viral replication. Thus, the aim of this work was to evaluate the anti-DENV effect of the Nordihydroguaiaretic acid (NDGA), a hypolipidemic agent with antioxidant and anti-inflammatory properties. A dose-dependent inhibition in viral yield and NS1 secretion was observed in supernatants of infected cells treated for 24 and 48 h with different concentrations of NDGA. To evaluate the effect of NDGA in DENV replication, a DENV4 replicon transfected Vero cells were treated with different concentrations of NDGA. NDGA treatment significantly reduced DENV replication, reiterating the importance of lipids in viral replication. NDGA treatment also led to reduction in number of lipid droplets (LDs), the neutral lipid storage organelles involved in DENV morphogenesis that are known to increase in number during DENV infection. Furthermore, NDGA treatment resulted in dissociation of the C protein from LDs. Overall our results suggest that NDGA inhibits DENV infection by targeting genome replication and viral assembly. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Morphogenesis of Tanzania guinea grass under nitrogen doses and plant densities

    Directory of Open Access Journals (Sweden)

    Thiago Gomes dos Santos Braz

    2011-07-01

    Full Text Available The objective of this work was to evaluate effects of nitrogen fertilization and plant density on morphogenesis of Tanzania guinea grass. It was used a random block design with 12 treatments and two replications in a 4 × 3 factorial arrangement, with four doses of nitrogen (N (without N application, 80, 160 or 320 kg/ha.year and three plant densities (9, 25 or 49 plants/m². Harvest was performed at 25 cm from the ground when the canopy intercepted 95% of the incident light. Rates of leaf appearance and pseudostem elongation were positively and linearly influenced by nitrogen, whereas phillochron and leaf life span were influenced linearly and negatively. Leaf elongation responded positively to two factors, whereas leaf senescence rate and number of live leaves were not influenced by the factors evaluated. Number of total, basal and aerial tillers were greater at the density of 9 plants/m² and at the nitrogen dose of 320 kg/ha.year. Nitrogen increases production of leaves and tillers in Tanzania guinea grass defoliated at 95% of light interception, but high density of plants reduces the number of tiller per bunch.

  10. Chondroitin 6-O-sulfotransferases are required for morphogenesis of the notochord in the ascidian embryo.

    Science.gov (United States)

    Nakamura, Jun; Yoshida, Keita; Sasakura, Yasunori; Fujiwara, Shigeki

    2014-12-01

    Chondroitin sulfate (CS) is a sulfated polysaccharide chain that binds to various core proteins to form proteoglycans. The amount and position of sulfate groups in CS are variable among different tissues, and are determined by specific sulfotransferases. Although the ascidians are the closest relatives of vertebrates, the functions of their sulfotransferases have not been studied. The genome of the ascidian Ciona intestinalis contains eight genes encoding proteins similar to chondroitin 6-O-sulfotransferases (C6STs), which appear to have independently diverged in the ascidian lineage during evolution. Among them, Ci-C6ST-like1 and Ci-C6ST-like7 were predominantly expressed in the developing notochord. In addition, they were weakly expressed in the neural tube. The disruption of either one of them affected the convergent extension movement of notochordal cells. Presumptive notochord cells coming from both sides of the embryo did not intercalate. The results suggest that both of them are necessary. In some cases, the anterior neural tube failed to close. Forced expression of Ci-C6ST-like1 or Ci-C6ST-like7 in the notochord restored the normal intercalation of notochordal cells, indicating that the effects of morpholino oligos are specific. Ci-C6ST-like1 and Ci-C6ST-like7 are required for the morphogenesis of the notochord in the ascidian embryo. © 2014 Wiley Periodicals, Inc.

  11. Mechanical feedback coordinates cell wall expansion and assembly in yeast mating morphogenesis

    Science.gov (United States)

    2018-01-01

    The shaping of individual cells requires a tight coordination of cell mechanics and growth. However, it is unclear how information about the mechanical state of the wall is relayed to the molecular processes building it, thereby enabling the coordination of cell wall expansion and assembly during morphogenesis. Combining theoretical and experimental approaches, we show that a mechanical feedback coordinating cell wall assembly and expansion is essential to sustain mating projection growth in budding yeast (Saccharomyces cerevisiae). Our theoretical results indicate that the mechanical feedback provided by the Cell Wall Integrity pathway, with cell wall stress sensors Wsc1 and Mid2 increasingly activating membrane-localized cell wall synthases Fks1/2 upon faster cell wall expansion, stabilizes mating projection growth without affecting cell shape. Experimental perturbation of the osmotic pressure and cell wall mechanics, as well as compromising the mechanical feedback through genetic deletion of the stress sensors, leads to cellular phenotypes that support the theoretical predictions. Our results indicate that while the existence of mechanical feedback is essential to stabilize mating projection growth, the shape and size of the cell are insensitive to the feedback. PMID:29346368

  12. Lack of protein-tyrosine sulfation disrupts photoreceptor outer segment morphogenesis, retinal function and retinal anatomy.

    Science.gov (United States)

    Sherry, David M; Murray, Anne R; Kanan, Yogita; Arbogast, Kelsey L; Hamilton, Robert A; Fliesler, Steven J; Burns, Marie E; Moore, Kevin L; Al-Ubaidi, Muayyad R

    2010-11-01

    To investigate the role(s) of protein-tyrosine sulfation in the retina, we examined retinal function and structure in mice lacking tyrosylprotein sulfotransferases (TPST) 1 and 2. Tpst double knockout (DKO; Tpst1(-/-) /Tpst2 (-/-) ) retinas had drastically reduced electroretinographic responses, although their photoreceptors exhibited normal responses in single cell recordings. These retinas appeared normal histologically; however, the rod photoreceptors had ultrastructurally abnormal outer segments, with membrane evulsions into the extracellular space, irregular disc membrane spacing and expanded intradiscal space. Photoreceptor synaptic terminals were disorganized in Tpst DKO retinas, but established ultrastructurally normal synapses, as did bipolar and amacrine cells; however, the morphology and organization of neuronal processes in the inner retina were abnormal. These results indicate that protein-tyrosine sulfation is essential for proper outer segment morphogenesis and synaptic function, but is not critical for overall retinal structure or synapse formation, and may serve broader functions in neuronal development and maintenance. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  13. Cell vertices as independent actors during cell intercalation in epithelial morphogenesis

    Science.gov (United States)

    Loerke, Dinah

    Epithelial sheets form the lining of organ surfaces and body cavities, and it is now appreciated that these sheets are dynamic structures that can undergo significant reorganizing events, e.g. during wound healing or morphogenesis. One of the key morphogenetic mechanisms that is utilized during development is tissue elongation, which is driven by oriented cell intercalation. In the Drosophila embryonic epithelium, this occurs through the contraction of vertical T1 interfaces and the subsequent resolution of horizontal T3 interfaces (analogous to so-called T1 transitions in soap foams), where the symmetry breaking behaviors are created by a system of planar polarity of actomyosin and adhesion complexes within the cell layer. The dominant physical model for this process posits that the anisotropy of line tension directs T1 contraction. However, this model is inconsistent with the in vivo observation that cell vertices of T1 interfaces lack physical coupling, and instead show independent movements. Thus, we propose that a more useful explanation of intercalary behaviors will be possible through a description of the radially-directed and adhesion-coupled force events that lead to vertex movements and produce subsequent dependent changes in interface lengths. This work is supported by NIH R15 GM117463-01 and by a Research Corporation for Science Advancement (RCSA) Cottrell Scholar Award.

  14. Structure, morphogenesis and evolutional transformation of winged fruits in representatives of the family Celastraceae R. Br.

    Directory of Open Access Journals (Sweden)

    I. A. Savinov

    2015-05-01

    Full Text Available Structure, peculiarities of morphogenesis and evolutional transformation of winged fruits in representatives of the family Celastraceae R. Br. are considered. Four types of such fruits are distinguished: I – winged fruits – fruits, outgrowths of which are formed due to radial expansion of the pericarp in the dorsal side of the carpel along the axis of the fruit (Tripterygioideae, subgenus Kalonymus genus Euonymus; II – the fruits with winged perianth – fruits, alar outgrowths of which are formed by elements of the perianth (Monimopetalum; III – divided winged fruit – divided fruits-capsules, wingshaped blades of which are formed from proliferating in the axial plane of the carpels (Hippocrateoideae; IV – winged schizocarpium – divided fruit, each mericarpium of which is provided by 3 alar vascularized outgrowths emerging due to the radial expansion of the pericarp from places of carpels fusion and in the dorsal side of the carpel along the axis of fruit (Stackhousioideae. We demonstrated that winged fruits appeared in different subfamilies and tribes.

  15. Glycosylphosphatidylinositol-anchored proteins are required for cell wall synthesis and morphogenesis in Arabidopsis.

    Science.gov (United States)

    Gillmor, C Stewart; Lukowitz, Wolfgang; Brininstool, Ginger; Sedbrook, John C; Hamann, Thorsten; Poindexter, Patricia; Somerville, Chris

    2005-04-01

    Mutations at five loci named PEANUT1-5 (PNT) were identified in a genetic screen for radially swollen embryo mutants. pnt1 cell walls showed decreased crystalline cellulose, increased pectins, and irregular and ectopic deposition of pectins, xyloglucans, and callose. Furthermore, pnt1 pollen is less viable than the wild type, and pnt1 embryos were delayed in morphogenesis and showed defects in shoot and root meristems. The PNT1 gene encodes the Arabidopsis thaliana homolog of mammalian PIG-M, an endoplasmic reticulum-localized mannosyltransferase that is required for synthesis of the glycosylphosphatidylinositol (GPI) anchor. All five pnt mutants showed strongly reduced accumulation of GPI-anchored proteins, suggesting that they all have defects in GPI anchor synthesis. Although the mutants are seedling lethal, pnt1 cells are able to proliferate for a limited time as undifferentiated callus and do not show the massive deposition of ectopic cell wall material seen in pnt1 embryos. The different phenotype of pnt1 cells in embryos and callus suggest a differential requirement for GPI-anchored proteins in cell wall synthesis in these two tissues and points to the importance of GPI anchoring in coordinated multicellular growth.

  16. Role of AtCDC48 & the AtCDC48 Regulatory Protein Family, PUX, in Plant Cell Morphogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Bednarek, Sebastian, Y.

    2009-11-08

    The long-term objective of this work is to understand the molecular events and mechanisms involved in secretory membrane trafficking and organelle biogenesis, which are crucial for normal plant growth and development. Our studies have suggested a vital role for the cytosolic chaperone Cdc48p/p97 during cytokinesis and cell expansion which are highly dependent upon secretory membrane trafficking. Localization studies have shown that the plant Cdc48p/p97, AtCDC48, and the Arabidopsis ortholog of the ER- and Golgi-associated SNARE, syntaxin 5, (referred to as SYP31) are targeted to the division plane during cytokinesis. In addition, AtCDC48 and SYP31 were shown to interact in vitro and in vivo. To characterize further the function of AtCDC48 and SYP31 we have utilized affinity chromatography and MALDI-MS to identify several plant-specific proteins that interact with SYP31 and/or modulate the activity of AtCDC48 including two UBX (i.e. ubiquitin-like) domain containing proteins, PUX1 and PUX2 (Proteins containing UBX domain). These proteins define a plant protein family consisting of 15 uncharacterized members that we postulate interact with AtCDC48. Biochemical studies have demonstrated that PUX2 is a novel membrane adapter for AtCDC48 that mediates AtCDC48/SYP31 interaction and is likely to control AtCDC48-dependent membrane fusion. In contrast, PUX1 negatively regulates AtCDC48 by inhibiting its ATPase activity and by promoting the disassembly of the active hexamer. These findings provide the first evidence that the assembly and disassembly of the CDC48/p97complex is actually a dynamic process. This new unexpected level of regulation for CDC48/p97 was demonstrated to be critical in vivo as pux1 loss-of-function mutants grow faster than wild-type plants. These studies suggest a role for AtCDC48 in plant cell cycle progression including cytokinesis and/or cell expansion. The proposed studies are designed to: 1) characterize further the localization and function of At

  17. Interference by 2,3,7,8-tetrachlorodibenzo-p-dioxin with cultured mouse submandibular gland branching morphogenesis involves reduced epidermal growth factor receptor signaling

    International Nuclear Information System (INIS)

    Kiukkonen, Anu; Sahlberg, Carin; Partanen, Anna-Maija; Alaluusua, Satu; Pohjanvirta, Raimo; Tuomisto, Jouko; Lukinmaa, Pirjo-Liisa

    2006-01-01

    Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to mouse embryonic teeth, sharing features of early development with salivary glands in common, involves enhanced apoptosis and depends on the expression of epidermal growth factor (EGF) receptor. EGF receptor signaling, on the other hand, is essential for salivary gland branching morphogenesis. To see if TCDD impairs salivary gland morphogenesis and if the impairment is associated with EGF receptor signaling, we cultured mouse (NMRI) E13 submandibular glands with TCDD or TCDD in combination with EGF or fibronectin (FN), both previously found to enhance branching morphogenesis. Explants were examined stereomicroscopically and processed to paraffin sections. TCDD exposure impaired epithelial branching and cleft formation, resulting in enlarged buds. The glands were smaller than normal. EGF and FN alone concentration-dependently stimulated or inhibited branching morphogenesis but when co-administered with TCDD, failed to compensate for its effect. TCDD induced cytochrome P4501A1 expression in the glandular epithelium, indicating activation of the aryl hydrocarbon receptor. TCDD somewhat increased epithelial apoptosis as observed by terminal deoxynucleotidyl transferase (TdT)-mediated nick end-labeling method but the increase could not be correlated with morphological changes. The frequency of proliferating cells was not altered. Corresponding to the reduced cleft sites in TCDD-exposed explants, FN immunoreactivity in the epithelium was reduced. The results show that TCDD, comparably with EGF and FN at morphogenesis-inhibiting concentrations, impaired salivary gland branching morphogenesis in vitro. Together with the failure of EGF and FN at morphogenesis-stimulating concentrations to compensate for the effect of TCDD this implies that TCDD toxicity to developing salivary gland involves reduced EGF receptor signaling

  18. Wnt5a regulates ventral midbrain morphogenesis and the development of A9-A10 dopaminergic cells in vivo

    Czech Academy of Sciences Publication Activity Database

    Andersson, E.R.; Prakash, N.; Čajánek, L.; Minina, E.; Bryja, Vítězslav; Bryjová, Lenka; Yamaguchi, T.P.; Hall, A.C.; Wurst, W.; Arenas, E.

    2008-01-01

    Roč. 3, č. 10 (2008), s. 1-14 E-ISSN 1932-6203 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : Wnt 5a deficient mouse * ventral midbrain * planar cell polarity Subject RIV: BO - Biophysics

  19. Cortical Morphogenesis during Embryonic Development Is Regulated by miR-34c and miR-204

    DEFF Research Database (Denmark)

    Veno, Morten T.; Veno, Susanne T.; Rehberg, Kati

    2017-01-01

    The porcine brain closely resembles the human brain in aspects such as development and morphology. Temporal miRNA profiling in the developing embryonic porcine cortex revealed a distinct set of miRNAs, including miR-34c and miR-204, which exhibited a highly specific expression profile across...

  20. Morphogenesis of mimivirus and its viral factories: an atomic force microscopy study of infected cells.

    Science.gov (United States)

    Kuznetsov, Yuri G; Klose, Thomas; Rossmann, Michael; McPherson, Alexander

    2013-10-01

    Amoebas infected with mimivirus were disrupted at sequential stages of virus production and were visualized by atomic force microscopy. The development of virus factories proceeded over 3 to 4 h postinfection and resulted from the coalescence of 0.5- to 2-μm vesicles, possibly bearing nucleic acid, derived from either the nuclear membrane or the closely associated rough endoplasmic reticulum. Virus factories actively producing virus capsids on their surfaces were imaged, and this allowed the morphogenesis of the capsids to be delineated. The first feature to appear on a virus factory surface when a new capsid is born is the center of a stargate, which is a pentameric protein oligomer. As the arms of the stargate grow from the pentamer, a rough disk the diameter of a capsid thickens around it. This marks the initial emergence of a protein-coated membrane vesicle. The capsid self-assembles on the vesicle. Hillocks capped by different pentameric proteins spontaneously appear on the emerging vesicle at positions that are ultimately occupied by 5-fold icosahedral vertices. A lattice of coat protein nucleates at each of the 5-fold vertices, but not at the stargate, and then spreads outward from the vertices over the surface, merging seamlessly to complete the icosahedral capsid. Filling with DNA and associated proteins occurs by the transfer of nucleic acid from the interior of the virus factory into the nearly completed capsids. The portal, through which the DNA enters, is sealed by a plug of protein having a diameter of about 40 nm. A layer of integument protein that anchors the surface fibers is acquired by the passage of capsids through a membrane enriched in the protein. The coating of surface fibers is similarly acquired when the integument protein-coated capsids pass through a second membrane that has a forest of surface fibers embedded on one side.

  1. Study on the pupal morphogenesis of Chrysomya rufifacies (Macquart) (Diptera: Calliphoridae) for postmortem interval estimation.

    Science.gov (United States)

    Ma, Ting; Huang, Jia; Wang, Jiang-Feng

    2015-08-01

    Chrysomya rufifacies (Macquart) is one of the most common species of blow flies at the scene of death in Southern China. Pupae are useful in postmortem interval (PMI) estimation due to their sedentary nature and longer duration of association with the corpse. However, to determine the age of a pupa is more difficult than that of a larva, due to the fact that morphological changes are rarely visible during pupal development. In this study, eggs of C. rufifacies were reared in climatic chambers under four different constant temperatures (20, 24, 28 and 32°C each±1°C, respectively) with same rearing conditions such as foodstuff, substrate, photoperiod and relative humidity. Ten duplicate pupae were sampled at 8-h intervals from prepupae to emergence under the different constant temperatures, respectively. The pupae were sampled, killed, fixed, dissected and with the puparium removed, the external morphological changes of the pupae were observed, recorded and photographed. The morphological characters of C. rufifacies pupae were described. Based on the visible external morphological characters during pupal morphogenesis at 28°C±1°C, the developmental period of C. rufifacies was divided into nine developmental stages and recorded in detailed description. Based on above-mentioned nine developmental stages, some visible external morphological characters were selected as indications for developmental stages. These indications mapped to 8-h sampling intervals at the four different constant temperatures were also described in this study. It is demonstrated that generally the duration of each developmental stage of C. rufifacies pupae is inversely correlated to appropriate developmental temperatures. This study provides relatively systematic pupal developmental data of C. rufifacies for the estimation of PMI. In addition, further work may improve by focus on other environmental factors, histological analysis, more thorough external examination by shortening sampling

  2. The CRC orthologue from Pisum sativum shows conserved functions in carpel morphogenesis and vascular development.

    Science.gov (United States)

    Fourquin, Chloé; Primo, Amparo; Martínez-Fernández, Irene; Huet-Trujillo, Estefanía; Ferrándiz, Cristina

    2014-11-01

    CRABS CLAW (CRC) is a member of the YABBY family of transcription factors involved in carpel morphogenesis, floral determinacy and nectary specification in arabidopsis. CRC orthologues have been functionally characterized across angiosperms, revealing additional roles in leaf vascular development and carpel identity specification in Poaceae. These studies support an ancestral role of CRC orthologues in carpel development, while roles in vascular development and nectary specification appear to be derived. This study aimed to expand research on CRC functional conservation to the legume family in order to better understand the evolutionary history of CRC orthologues in angiosperms. CRC orthologues from Pisum sativum and Medicago truncatula were identified. RNA in situ hybridization experiments determined the corresponding expression patterns throughout flower development. The phenotypic effects of reduced CRC activity were investigated in P. sativum using virus-induced gene silencing. CRC orthologues from P. sativum and M. truncatula showed similar expression patterns, mainly restricted to carpels and nectaries. However, these expression patterns differed from those of other core eudicots, most importantly in a lack of abaxial expression in the carpel and in atypical expression associated with the medial vein of the ovary. CRC downregulation in pea caused defects in carpel fusion and style/stigma development, both typically associated with CRC function in eudicots, but also affected vascular development in the carpel. The data support the conserved roles of CRC orthologues in carpel fusion, style/stigma development and nectary development. In addition, an intriguing new aspect of CRC function in legumes was the unexpected role in vascular development, which could be shared by other species from widely diverged clades within the angiosperms, suggesting that this role could be ancestral rather than derived, as so far generally accepted. © The Author 2014. Published by

  3. Zygotic and somatic embryo morphogenesis in Pinus pinaster: comparative histological and histochemical study.

    Science.gov (United States)

    Tereso, Susana; Zoglauer, Kurt; Milhinhos, Ana; Miguel, Célia; Oliveira, M Margarida

    2007-05-01

    We compared morphogenesis and accumulation of storage proteins and starch in Pinus pinaster Ait. zygotic embryos with those in somatic embryos grown with different carbohydrate sources. The maturation medium for somatic embryos included 80 microM abscisic acid (ABA), 9 g l(-1) gellam gum and either glucose, sucrose or maltose at 44, 88, 175 or 263 mM in the presence or absence of 6% (w/v) polyethylene glycol (PEG) 4000 MW. Maturation medium containing 44 or 88 mM of a carbohydrate source produced only one or no cotyledonary somatic embryos per 0.6 g fresh mass of culture. The addition of PEG to the basal maturation medium resulted in a low yield of cotyledonary somatic embryos that generally showed incomplete development and anatomical abnormalities such as large intercellular spaces and large vacuoles. High concentrations of maltose also induced large intercellular spaces in the somatic embryonic cells, and 263 mM sucrose produced fewer and less developed cotyledonary somatic embryos compared with 175 mM sucrose, indicating that the effect of carbohydrate source is partially osmotic. Zygotic embryos had a lower dry mass than somatic embryos at the same stage of development. Starch granules followed a similar accumulation pattern in zygotic and somatic embryos. A low starch content was found in cotyledonary zygotic embryos and in somatic embryos developed in the presence of 175 mM maltose or 263 mM glucose. In zygotic embryos and in PEG-treated somatic embryos, protein bodies appeared later and were smaller and fewer than in well-developed somatic embryos grown without PEG. We propose that storage protein concentration might be a marker of embryo quality.

  4. Floral morphology and morphogenesis in Camptotheca (Nyssaceae), and its systematic significance.

    Science.gov (United States)

    Gong, Jing-Zhi; Li, Qiu-Jie; Wang, Xi; Ma, Yue-Ping; Zhang, Xiao-Hui; Zhao, Liang; Chang, Zhao-Yang; Ronse De Craene, Louis

    2018-03-22

    Camptotheca is endemic to China and there are limited data about the breeding system and morphogenesis of the flowers. Camptotheca is thought to be related to Nyssa and Davidia in Nyssaceae, which has sometimes been included in Cornaceae. However, molecular phylogenetic studies confirmed the inclusion of Camptotheca in Nyssaceae and its exclusion from Cornaceae. The aim of this study was to reveal developmental features of the inflorescence and flowers in Camptotheca to compare with related taxa in Cornales. Inflorescences and flowers of Camptotheca acuminata at all developmental stages were collected and studied with a scanning electron microscope and stereo microscope. Camptotheca has botryoids which are composed of several capitate floral units (FUs) that are initiated acropetally. On each FU, flowers are grouped in dyads that are initiated acropetally. All floral organs are initiated centripetally. Calyx lobes are restricted to five teeth. The hypanthium, with five toothed calyx lobes, is adnate to the ovary. The five petals are free and valvate. Ten stamens are inserted in two whorls around the central depression, in which the style is immersed. Three carpels are initiated independently but the ovary is syncarpous and unilocular. The ovule is unitegmic and heterotropous. Inflorescences are functionally andromonoecious varying with the position of the FUs on the inflorescence system. Flowers on the upper FU often have robust styles and fully developed ovules. Flowers on the lower FU have undeveloped styles and aborted ovules, and the flowers on the middle FU are transitional. Camptotheca possesses several traits that unify it with Nyssa, Mastixia and Diplopanax. Inflorescence and floral characters support a close relationship with Nyssaceae and Mastixiaceae but a distant relationship with Cornus. Our results corroborate molecular inferences and support a separate family Nyssaceae.

  5. The PCP genes Celsr1 and Vangl2 are required for normal lung branching morphogenesis

    Science.gov (United States)

    Yates, Laura L.; Schnatwinkel, Carsten; Murdoch, Jennifer N.; Bogani, Debora; Formstone, Caroline J.; Townsend, Stuart; Greenfield, Andy; Niswander, Lee A.; Dean, Charlotte H.

    2010-01-01

    The lungs are generated by branching morphogenesis as a result of reciprocal signalling interactions between the epithelium and mesenchyme during development. Mutations that disrupt formation of either the correct number or shape of epithelial branches affect lung function. This, in turn, can lead to congenital abnormalities such as cystadenomatoid malformations, pulmonary hypertension or lung hypoplasia. Defects in lung architecture are also associated with adult lung disease, particularly in cases of idiopathic lung fibrosis. Identifying the signalling pathways which drive epithelial tube formation will likely shed light on both congenital and adult lung disease. Here we show that mutations in the planar cell polarity (PCP) genes Celsr1 and Vangl2 lead to disrupted lung development and defects in lung architecture. Lungs from Celsr1Crsh and Vangl2Lp mouse mutants are small and misshapen with fewer branches, and by late gestation exhibit thickened interstitial mesenchyme and defective saccular formation. We observe a recapitulation of these branching defects following inhibition of Rho kinase, an important downstream effector of the PCP signalling pathway. Moreover, epithelial integrity is disrupted, cytoskeletal remodelling perturbed and mutant endoderm does not branch normally in response to the chemoattractant FGF10. We further show that Celsr1 and Vangl2 proteins are present in restricted spatial domains within lung epithelium. Our data show that the PCP genes Celsr1 and Vangl2 are required for foetal lung development thereby revealing a novel signalling pathway critical for this process that will enhance our understanding of congenital and adult lung diseases and may in future lead to novel therapeutic strategies. PMID:20223754

  6. Expression of a putative grapevine hexose transporter in tobacco alters morphogenesis and assimilate partitioning.

    Science.gov (United States)

    Leterrier, Marina; Atanassova, Rossitza; Laquitaine, Laurent; Gaillard, Cécile; Coutos-Thévenot, Pierre; Delrot, Serge

    2003-04-01

    Tobacco plants were transformed by leaf disc regeneration with the VvHT1 (Vitis vinifera hexose transporter 1) cDNA under the control of the constitutive CaMV 35S promoter in a sense or antisense orientation. Among the 20 sense plants and 10 antisense plants obtained, two sense plants showed a mutant phenotype when grown in vitro, with stunted growth and an increase in the (leaves+stem)/roots dry weight ratio. The rate of [(3)H]-glucose uptake in leaf discs from these plants was decreased to 25% of the value measured in control plants. The amount of VvHT1 transgene and of host monosaccharide transporter MST transcripts in the leaves were studied by RNA gel blot analysis. The VvHT1 transcripts were usually present, but the amount of MST transcripts was the lowest in the plants that exhibited the most marked phenotype. Although the phenotype was lost when the plants were transferred from in vitro to greenhouse conditions, it was found again in vitro in the progeny obtained by self-pollination or by back-cross. The data show that VvHT1 sense expression resulted in unidirectional post-transcriptional gene inactivation of MST in some of the transformants, with dramatic effects on growth. They provide the first example of plants modified for hexose transport by post-transcriptional gene silencing. Some of the antisense plants also showed reduced expression of MST, and decreased growth. These results indicate that, like the sucrose transporters, hexose transporters play an important role in assimilate transport and in morphogenesis.

  7. Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation

    Science.gov (United States)

    Niessen, Carien M.; Leckband, Deborah; Yap, Alpha S.

    2013-01-01

    This review addresses the cellular and molecular mechanisms of cadherin-based tissue morphogenesis. Tissue physiology is profoundly influenced by the distinctive organizations of cells in organs and tissues. In metazoa, adhesion receptors of the classical cadherin family play important roles in establishing and maintaining such tissue organization. Indeed, it is apparent that cadherins participate in a range of morphogenetic events that range from support of tissue integrity to dynamic cellular rearrangements. A comprehensive understanding of cadherin-based morphogenesis must then define the molecular and cellular mechanisms that support these distinct cadherin biologies. Here we focus on four key mechanistic elements: the molecular basis for adhesion through cadherin ectodomains; the regulation of cadherin expression at the cell surface; cooperation between cadherins and the actin cytoskeleton; and regulation by cell signaling. We discuss current progress and outline issues for further research in these fields. PMID:21527735

  8. Full-Length Fibronectin Drives Fibroblast Accumulation at the Surface of Collagen Microtissues during Cell-Induced Tissue Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Jasper Foolen

    Full Text Available Generating and maintaining gradients of cell density and extracellular matrix (ECM components is a prerequisite for the development of functionality of healthy tissue. Therefore, gaining insights into the drivers of spatial organization of cells and the role of ECM during tissue morphogenesis is vital. In a 3D model system of tissue morphogenesis, a fibronectin-FRET sensor recently revealed the existence of two separate fibronectin populations with different conformations in microtissues, i.e. 'compact and adsorbed to collagen' versus 'extended and fibrillar' fibronectin that does not colocalize with the collagen scaffold. Here we asked how the presence of fibronectin might drive this cell-induced tissue morphogenesis, more specifically the formation of gradients in cell density and ECM composition. Microtissues were engineered in a high-throughput model system containing rectangular microarrays of 12 posts, which constrained fibroblast-populated collagen gels, remodeled by the contractile cells into trampoline-shaped microtissues. Fibronectin's contribution during the tissue maturation process was assessed using fibronectin-knockout mouse embryonic fibroblasts (Fn-/- MEFs and floxed equivalents (Fnf/f MEFs, in fibronectin-depleted growth medium with and without exogenously added plasma fibronectin (full-length, or various fragments. In the absence of full-length fibronectin, Fn-/- MEFs remained homogenously distributed throughout the cell-contracted collagen gels. In contrast, in the presence of full-length fibronectin, both cell types produced shell-like tissues with a predominantly cell-free compacted collagen core and a peripheral surface layer rich in cells. Single cell assays then revealed that Fn-/- MEFs applied lower total strain energy on nanopillar arrays coated with either fibronectin or vitronectin when compared to Fnf/f MEFs, but that the presence of exogenously added plasma fibronectin rescued their contractility. While collagen

  9. Characterization of a putative spindle assembly checkpoint kinase Mps1, suggests its involvement in cell division, morphogenesis and oxidative stress tolerance in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Mohan Kamthan

    Full Text Available In Saccharomyces cerevisiae MPS1 is one of the major protein kinase that governs the spindle checkpoint pathway. The S. cerevisiae structural homolog of opportunistic pathogen Candida albicans CaMPS1, is indispensable for the cell viability. The essentiality of Mps1 was confirmed by Homozygote Trisome test. To determine its biological function in this pathogen conditional mutant was generated through regulatable MET3 promoter. Examination of heterozygous and conditional (+Met/Cys mps1 mutants revealed a mitosis specific arrest phenotype, where mutants showed large buds with undivided nuclei. Flowcytometry analysis revealed abnormal ploidy levels in mps1 mutant. In presence of anti-microtubule drug Nocodazole, mps1 mutant showed a dramatic loss of viability suggesting a role of Mps1 in Spindle Assembly Checkpoint (SAC activation. These mutants were also defective in microtubule organization. Moreover, heterozygous mutant showed defective in-vitro yeast to hyphae morphological transition. Growth defect in heterozygous mutant suggest haploinsufficiency of this gene. qRT PCR analysis showed around 3 fold upregulation of MPS1 in presence of serum. This expression of MPS1 is dependent on Efg1 and is independent of other hyphal regulators like Ras1 and Tpk2. Furthermore, mps1 mutants were also sensitive to oxidative stress. Heterozygous mps1 mutant did not undergo morphological transition and showed 5-Fold reduction in colony forming units in response to macrophage. Thus, the vital checkpoint kinase, Mps1 besides cell division also has a role in morphogenesis and oxidative stress tolerance, in this pathogenic fungus.

  10. Caenorhabditis elegans histone deacetylase hda-1 is required for morphogenesis of the vulva and LIN-12/Notch-mediated specification of uterine cell fates.

    Science.gov (United States)

    Ranawade, Ayush Vasant; Cumbo, Philip; Gupta, Bhagwati P

    2013-08-07

    Chromatin modification genes play crucial roles in development and disease. In Caenorhabditis elegans, the class I histone deacetylase family member hda-1, a component of the nucleosome remodeling and deacetylation complex, has been shown to control cell proliferation. We recovered hda-1 in an RNA interference screen for genes involved in the morphogenesis of the egg-laying system. We found that hda-1 mutants have abnormal vulva morphology and vulval-uterine connections (i.e., no uterine-seam cell). We characterized the vulval defects by using cell fate-specific markers and found that hda-1 is necessary for the specification of all seven vulval cell types. The analysis of the vulval-uterine connection defect revealed that hda-1 is required for the differentiation of the gonadal anchor cell (AC), which in turn induces ventral uterine granddaughters to adopt π fates, leading to the formation of the uterine-seam cell. Consistent with these results, hda-1 is expressed in the vulva and AC. A search for hda-1 target genes revealed that fos-1 (fos proto-oncogene family) acts downstream of hda-1 in vulval cells, whereas egl-43 (evi1 proto-oncogene family) and nhr-67 (tailless homolog, NHR family) mediate hda-1 function in the AC. Furthermore, we showed that AC expression of hda-1 plays a crucial role in the regulation of the lin-12/Notch ligand lag-2 to specify π cell fates. These results demonstrate the pivotal role of hda-1 in the formation of the vulva and the vulval-uterine connection. Given that hda-1 homologs are conserved across the phyla, our findings are likely to provide a better understanding of HDAC1 function in development and disease.

  11. Alteration in the ultrastructural morphology of mycelial hyphae and the dynamics of transcriptional activity of lytic enzyme genes during basidiomycete morphogenesis.

    Science.gov (United States)

    Vetchinkina, Elena; Kupryashina, Maria; Gorshkov, Vladimir; Ageeva, Marina; Gogolev, Yuri; Nikitina, Valentina

    2017-04-01

    The morphogenesis of macromycetes is a complex multilevel process resulting in a set of molecular-genetic, physiological-biochemical, and morphological-ultrastructural changes in the cells. When the xylotrophic basidiomycetes Lentinus edodes, Grifola frondosa, and Ganoderma lucidum were grown on wood waste as the substrate, the ultrastructural morphology of the mycelial hyphal cell walls differed considerably between mycelium and morphostructures. As the macromycetes passed from vegetative to generative development, the expression of the tyr1, tyr2, chi1, chi2, exg1, exg2, and exg3 genes was activated. These genes encode enzymes such as tyrosinase, chitinase, and glucanase, which play essential roles in cell wall growth and morphogenesis.

  12. Divergent axial morphogenesis and early shh expression in vertebrate prospective floor plate

    Directory of Open Access Journals (Sweden)

    Stanislav Kremnyov

    2018-01-01

    Full Text Available Abstract Background The notochord has organizer properties and is required for floor plate induction and dorsoventral patterning of the neural tube. This activity has been attributed to sonic hedgehog (shh signaling, which originates in the notochord, forms a gradient, and autoinduces shh expression in the floor plate. However, reported data are inconsistent and the spatiotemporal development of the relevant shh expression domains has not been studied in detail. We therefore studied the expression dynamics of shh in rabbit, chicken and Xenopus laevis embryos (as well as indian hedgehog and desert hedgehog as possible alternative functional candidates in the chicken. Results Our analysis reveals a markedly divergent pattern within these vertebrates: whereas in the rabbit shh is first expressed in the notochord and its floor plate domain is then induced during subsequent somitogenesis stages, in the chick embryo shh is expressed in the prospective neuroectoderm prior to the notochord formation and, interestingly, prior to mesoderm immigration. Neither indian hedgehog nor desert hedgehog are expressed in these midline structures although mRNA of both genes was detected in other structures of the early chick embryo. In X. laevis, shh is expressed at the beginning of gastrulation in a distinct area dorsal to the dorsal blastopore lip and adjacent to the prospective neuroectoderm, whereas the floor plate expresses shh at the end of gastrulation. Conclusions While shh expression patterns in rabbit and X. laevis embryos are roughly compatible with the classical view of “ventral to dorsal induction” of the floor plate, the early shh expression in the chick floor plate challenges this model. Intriguingly, this alternative sequence of domain induction is related to the asymmetrical morphogenesis of the primitive node and other axial organs in the chick. Our results indicate that the floor plate in X. laevis and chick embryos may be initially

  13. The effects of the exopolysaccharide and growth rate on the morphogenesis of the terrestrial filamentous cyanobacterium Nostoc flagelliforme

    Directory of Open Access Journals (Sweden)

    Lijuan Cui

    2017-09-01

    Full Text Available The terrestrial cyanobacterium Nostoc flagelliforme, which contributes to carbon and nitrogen supplies in arid and semi-arid regions, adopts a filamentous colony form. Owing to its herbal and dietary values, this species has been overexploited. Largely due to the lack of understanding on its morphogenesis, artificial cultivation has not been achieved. Additionally, it may serve as a useful model for recognizing the morphological adaptation of colonial cyanobacteria in terrestrial niches. However, it shows very slow growth in native habitats and is easily disintegrated under laboratory conditions. Thus, a novel experimental system is necessary to explore its morphogenetic mechanism. Liquid-cultured N. flagelliforme has been well developed for exopolysaccharide (EPS production, in which microscopic colonies (micro-colonies are generally formed. In this study, we sought to gain some insight into the morphogenesis of N. flagelliforme by examining the effects of two external factors, the EPS and environmental stress-related growth rate, on the morphological shaping of micro-colonies. Our findings indicate that the EPS matrix could act as a basal barrier, leading to the bending of trichomes during their elongation, while very slow growth is conducive to their straight elongation. These findings will guide future cultivation and application of this cyanobacterium for ecological improvement.

  14. Engineering strategies to recapitulate epithelial morphogenesis within synthetic three-dimensional extracellular matrix with tunable mechanical properties

    International Nuclear Information System (INIS)

    Miroshnikova, Y A; Sarang-Sieminski, A L; Jorgens, D M; Auer, M; Spirio, L; Weaver, V M

    2011-01-01

    The mechanical properties (e.g. stiffness) of the extracellular matrix (ECM) influence cell fate and tissue morphogenesis and contribute to disease progression. Nevertheless, our understanding of the mechanisms by which ECM rigidity modulates cell behavior and fate remains rudimentary. To address this issue, a number of two and three-dimensional (3D) hydrogel systems have been used to explore the effects of the mechanical properties of the ECM on cell behavior. Unfortunately, many of these systems have limited application because fiber architecture, adhesiveness and/or pore size often change in parallel when gel elasticity is varied. Here we describe the use of ECM-adsorbed, synthetic, self-assembling peptide (SAP) gels that are able to recapitulate normal epithelial acini morphogenesis and gene expression in a 3D context. By exploiting the range of viscoelasticity attainable with these SAP gels, and their ability to recreate native-like ECM fibril topology with minimal variability in ligand density and pore size, we were able to reconstitute normal and tumor-like phenotypes and gene expression patterns in nonmalignant mammary epithelial cells. Accordingly, this SAP hydrogel system presents the first tunable system capable of independently assessing the interplay between ECM stiffness and multi-cellular epithelial phenotype in a 3D context

  15. Impaired hair follicle morphogenesis and polarized keratinocyte movement upon conditional inactivation of integrin-linked kinase in the epidermis.

    Science.gov (United States)

    Nakrieko, Kerry-Ann; Welch, Ian; Dupuis, Holly; Bryce, Dawn; Pajak, Agnieszka; St Arnaud, René; Dedhar, Shoukat; D'Souza, Sudhir J A; Dagnino, Lina

    2008-04-01

    Integrin-linked kinase (ILK) is key for cell survival, migration, and adhesion, but little is known about its role in epidermal development and homeostasis in vivo. We generated mice with conditional inactivation of the Ilk gene in squamous epithelia. These mice die perinatally and exhibit skin blistering and severe defects in hair follicle morphogenesis, including greatly reduced follicle numbers, failure to progress beyond very early developmental stages, and pronounced defects in follicular keratinocyte proliferation. ILK-deficient epidermis shows abnormalities in adhesion to the basement membrane and in differentiation. ILK-deficient cultured keratinocytes fail to attach and spread efficiently and exhibit multiple abnormalities in actin cytoskeletal organization. Ilk gene inactivation in cultured keratinocytes causes impaired ability to form stable lamellipodia, to directionally migrate, and to polarize. These defects are accompanied by abnormal distribution of active Cdc42 to cell protrusions, as well as reduced activation of Rac1 upon induction of cell migration in scraped keratinocyte monolayers. Significantly, alterations in cell spreading and forward movement in single cells can be rescued by expression of constitutively active Rac1 or RhoG. Our studies underscore a central and distinct role for ILK in hair follicle development and in polarized cell movements, two key aspects of epithelial morphogenesis and function.

  16. Bacteria-induced morphogenesis of Ulva intestinalis and Ulva mutabilis (Chlorophyta): a contribution to the lottery theory.

    Science.gov (United States)

    Ghaderiardakani, Fatemeh; Coates, Juliet C; Wichard, Thomas

    2017-08-01

    The green marine macroalgae of the class Ulvophyceae (Ulvophytes) are common algae distributed worldwide particularly in intertidal areas, which play a key role in aquatic ecosystems. They are potentially valuable resources for food, animal feed and fuel but can also cause massive nuisance blooms. Members of Ulvaceae, like many other seaweeds, harbour a rich diversity of epiphytic bacteria with functions related to host growth and morphological development. In the absence of appropriate bacterially derived signals, germ cells of the genus Ulva develop into 'atypical' colonies consisting of undifferentiated cells with abnormal cell walls. This paper examines the specificity of bacteria-induced morphogenesis in Ulva, by cross-testing bacteria isolated from several Ulva species on two Ulva species, the emerging model system Ulva mutabilis and the prominent biofouler species Ulva intestinalis. We show that pairs of bacterial strains isolated from species other than U. mutabilis and U. intestinalis can fully rescue axenic plantlets generated either from U. mutabilis or U. intestinalis gametes. This laboratory-based study demonstrates that different compositions of microbial communities with similar functional characteristics can enable complete algal morphogenesis and thus supports the 'competitive lottery' theory for how symbiotic bacteria drive algal development. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. A noncanonical auxin-sensing mechanism is required for organ morphogenesis in arabidopsis

    NARCIS (Netherlands)

    Simonini, Sara; Deb, Joyita; Moubayidin, Laila; Stephenson, Pauline; Valluru, Manoj; Freire-Rios, Alejandra; Sorefan, Karim; Weijers, Dolf; Friml, Jiří; Østergaard, Lars

    2016-01-01

    Tissue patterning in multicellular organisms is the output of precise spatio–temporal regulation of gene expression coupled with changes in hormone dynamics. In plants, the hormone auxin regulates growth and development at every stage of a plant’s life cycle. Auxin signaling occurs through

  18. The MARVEL domain protein Nce102 regulates actin organization and invasive growth of Candida albicans.

    Science.gov (United States)

    Douglas, Lois M; Wang, Hong X; Konopka, James B

    2013-11-26

    Invasive growth of the fungal pathogen Candida albicans into tissues promotes disseminated infections in humans. The plasma membrane is essential for pathogenesis because this important barrier mediates morphogenesis and invasive growth, as well as secretion of virulence factors, cell wall synthesis, nutrient import, and other processes. Previous studies showed that the Sur7 tetraspan protein that localizes to MCC (membrane compartment occupied by Can1)/eisosome subdomains of the plasma membrane regulates a broad range of key functions, including cell wall synthesis, morphogenesis, and resistance to copper. Therefore, a distinct tetraspan protein found in MCC/eisosomes, Nce102, was investigated. Nce102 belongs to the MARVEL domain protein family, which is implicated in regulating membrane structure and function. Deletion of NCE102 did not cause the broad defects seen in sur7Δ cells. Instead, the nce102Δ mutant displayed a unique phenotype in that it was defective in forming hyphae and invading low concentrations of agar but could invade well in higher agar concentrations. This phenotype was likely due to a defect in actin organization that was observed by phalloidin staining. In support of this, the invasive growth defect of a bni1Δ mutant that mislocalizes actin due to lack of the Bni1 formin was also reversed at high agar concentrations. This suggests that a denser matrix provides a signal that compensates for the actin defects. The nce102Δ mutant displayed decreased virulence and formed abnormal hyphae in mice. These studies identify novel ways that Nce102 and the physical environment surrounding C. albicans regulate morphogenesis and pathogenesis. The plasma membrane promotes virulence of the human fungal pathogen Candida albicans by acting as a protective barrier around the cell and mediating dynamic activities, such as morphogenesis, cell wall synthesis, secretion of virulence factors, and nutrient uptake. To better understand how the plasma membrane

  19. The influence of matrix properties on growth and morphogenesis of human pancreatic ductal epithelial cells in 3D

    Science.gov (United States)

    Raza, Asad; Ki, Chang Seok; Lin, Chien-Chi

    2013-01-01

    A highly tunable synthetic biomimetic hydrogel platform was developed to study the growth and morphogenesis of pancreatic ductal epithelial cells (PDEC) under the influence of a myriad of instructive cues. A PDEC line, PANC-1, was used as a model system to illustrate the importance of matrix compositions on cell fate determination. PANC-1 is an immortalized ductal epithelial cell line widely used in the study of pancreatic tumor cell behaviors. PANC-1 cells are also increasingly explored as a potential cell source for endocrine differentiation. Thus far, most studies related to PANC-1, among other PDEC lines, are performed on 2D culture surfaces. Here, we evaluated the effect of matrix compositions on PANC-1 cell growth and morphogenesis in 3D. Specifically, PANC-1 cells were encapsulated in PEG-based hydrogels prepared by step-growth thiol-ene photopolymerization. It was found that thiol-ene hydrogels provided a cytocompatible environment for encapsulation and 3D culture of PANC-1 cells. In contrast to a monolayer morphology on 2D culture surfaces, PANC-1 cells formed clusters in 3D thiol-ene hydrogels within 4 days of culture. After culturing for 10 days, however, the growth and structures of these clusters were significantly impacted by gel matrix properties, including sensitivity of the matrix to proteases, stiffness of the matrix, and ECM-mimetic motifs. The use of matrix metalloproteinase (MMP) sensitive linker or the immobilization of fibronectin-derived RGDS ligand in the matrix promoted PANC-1 cell growth and encouraged them to adopt ductal cyst-like structures. On the other hand, the encapsulated cells formed smaller and more compact aggregates in non-MMP responsive gels. The incorporation of laminin-derived YIGSR peptide did not enhance cell growth and caused the cells to form compact aggregates. Immobilized YIGSR also enhanced the expression of epithelial cell markers including β-catenin and E-cadherin. These studies have established PEG

  20. ANGUSTIFOLIA mediates one of the multiple SCRAMBLED signaling pathways regulating cell growth pattern in Arabidopsis thaliana.

    Science.gov (United States)

    Kwak, Su-Hwan; Song, Sang-Kee; Lee, Myeong Min; Schiefelbein, John

    2015-09-25

    In Arabidopsis thaliana, an atypical leucine-rich repeat receptor-like kinase, SCRAMBLED (SCM), is required for multiple developmental processes including root epidermal cell fate determination, silique dehiscence, inflorescence growth, ovule morphogenesis, and tissue morphology. Previous work suggested that SCM regulates these multiple pathways using distinct mechanisms via interactions with specific downstream factors. ANGUSTIFOLIA (AN) is known to regulate cell and tissue morphogenesis by influencing cortical microtubule arrangement, and recently, the AN protein was reported to interact with the SCM protein. Therefore, we examined whether AN might be responsible for mediating some of the SCM-dependent phenotypes. We discovered that both scm and an mutant lines cause an abnormal spiral or twisting growth of roots, but only the scm mutant affected root epidermal patterning. The siliques of the an and scm mutants also exhibited spiral growth, as previously reported, but only the scm mutant altered silique dehiscence. Interestingly, we discovered that the spiral growth of roots and siliques of the scm mutant is rescued by a truncated SCM protein that lacks its kinase domain, and that a juxtamembrane domain of SCM was sufficient for AN binding in the yeast two-hybrid analysis. These results suggest that the AN protein is one of the critical downstream factors of SCM pathways specifically responsible for mediating its effects on cell/tissue morphogenesis through cortical microtubule arrangement. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. The Role of Sonic Hedgehog in Craniofacial Patterning, Morphogenesis and Cranial Neural Crest Survival.

    Science.gov (United States)

    Dworkin, Sebastian; Boglev, Yeliz; Owens, Harley; Goldie, Stephen J

    2016-08-03

    Craniofacial defects (CFD) are a significant healthcare problem worldwide. Understanding both the morphogenetic movements which underpin normal facial development, as well as the molecular factors which regulate these processes, forms the cornerstone of future diagnostic, and ultimately, preventative therapies. The soluble morphogen Sonic hedgehog ( Shh ), a vertebrate orthologue of Drosophila hedgehog , is a key signalling factor in the regulation of craniofacial skeleton development in vertebrates, operating within numerous tissue types in the craniofacial primordia to spatiotemporally regulate the formation of the face and jaws. This review will provide an overview of normal craniofacial skeleton development, and focus specifically on the known roles of Shh in regulating the development and progression of the first pharyngeal arch, which in turn gives rise to both the upper jaw (maxilla) and lower jaw (mandible).

  2. The Role of Sonic Hedgehog in Craniofacial Patterning, Morphogenesis and Cranial Neural Crest Survival

    Directory of Open Access Journals (Sweden)

    Sebastian Dworkin

    2016-08-01

    Full Text Available Craniofacial defects (CFD are a significant healthcare problem worldwide. Understanding both the morphogenetic movements which underpin normal facial development, as well as the molecular factors which regulate these processes, forms the cornerstone of future diagnostic, and ultimately, preventative therapies. The soluble morphogen Sonic hedgehog (Shh, a vertebrate orthologue of Drosophila hedgehog, is a key signalling factor in the regulation of craniofacial skeleton development in vertebrates, operating within numerous tissue types in the craniofacial primordia to spatiotemporally regulate the formation of the face and jaws. This review will provide an overview of normal craniofacial skeleton development, and focus specifically on the known roles of Shh in regulating the development and progression of the first pharyngeal arch, which in turn gives rise to both the upper jaw (maxilla and lower jaw (mandible.

  3. Three-dimensional lithographically-defined organotypic tissue arrays for quantitative analysis of morphogenesis and neoplastic progression

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Celeste M.; Inman, Jamie L.; Bissell, Mina J.

    2008-02-13

    Here we describe a simple micromolding method to construct three-dimensional arrays of organotypic epithelial tissue structures that approximate in vivo histology. An elastomeric stamp containing an array of posts of defined geometry and spacing is used to mold microscale cavities into the surface of type I collagen gels. Epithelial cells are seeded into the cavities and covered with a second layer of collagen. The cells reorganize into hollow tissues corresponding to the geometry of the cavities. Patterned tissue arrays can be produced in 3-4 h and will undergo morphogenesis over the following one to three days. The protocol can easily be adapted to study a variety of tissues and aspects of normal and neoplastic development.

  4. Morphogenesis and tissue culture of sweet orange (Citrus sinensis (L.) Osb.): effect of temperature and photosynthetic radiation

    International Nuclear Information System (INIS)

    Duran-Vila, N.; Gogorcena, Y.; Ortega, V.; Ortiz, J.; Navarro, L.

    1992-01-01

    Both incubation temperature and photosynthetic radiation affected morphogenesis, callus culture and plantlet culture of sweet orange (Citrus sinensis) cultured in vitro. Bud culture from nodal stem segments, regeneration of shoots and buds from internode stem segments and induction of primary callus were near optimal at incubation temperatures between 21–30°C. The optimal temperature for root formation was 27°C with temperatures above and below being clearly deleterious. Incubation in the dark or under low photosynthetic photon flux density (PPFD) was beneficial for callus induction and growth and also favored the production of rooted plantlets from bud cultures. Incubation in the dark improved considerably the regeneration of shoots and buds from internode segments and the recovery of whole plants. No off-types, as determined by protein and isoenzyme analysis, were observed among plantlets recovered from bud cultures or from regeneration of shoots from internode stem segments

  5. MicroRNA-200c-141 and ∆Np63 are required for breast epithelial differentiation and branching morphogenesis.

    Science.gov (United States)

    Hilmarsdóttir, Bylgja; Briem, Eirikur; Sigurdsson, Valgardur; Franzdóttir, Sigrídur Rut; Ringnér, Markus; Arason, Ari Jon; Bergthorsson, Jon Thor; Magnusson, Magnus Karl; Gudjonsson, Thorarinn

    2015-07-15

    The epithelial compartment of the breast contains two lineages, the luminal- and the myoepithelial cells. D492 is a breast epithelial cell line with stem cell properties that forms branching epithelial structures in 3D culture with both luminal- and myoepithelial differentiation. We have recently shown that D492 undergo epithelial to mesenchymal transition (EMT) when co-cultured with endothelial cells. This 3D co-culture model allows critical analysis of breast epithelial lineage development and EMT. In this study, we compared the microRNA (miR) expression profiles for D492 and its mesenchymal-derivative D492M. Suppression of the miR-200 family in D492M was among the most profound changes observed. Exogenous expression of miR-200c-141 in D492M reversed the EMT phenotype resulting in gain of luminal but not myoepithelial differentiation. In contrast, forced expression of ∆Np63 in D492M restored the myoepithelial phenotype only. Co-expression of miR-200c-141 and ∆Np63 in D492M restored the branching morphogenesis in 3D culture underlining the requirement for both luminal and myoepithelial elements for obtaining full branching morphogenesis in breast epithelium. Introduction of a miR-200c-141 construct in both D492 and D492M resulted in resistance to endothelial induced EMT. In conclusion, our data suggests that expression of miR-200c-141 and ∆Np63 in D492M can reverse EMT resulting in luminal- and myoepithelial differentiation, respectively, demonstrating the importance of these molecules in epithelial integrity in the human breast. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Overexpression of Robo2 causes defects in the recruitment of metanephric mesenchymal cells and ureteric bud branching morphogenesis

    International Nuclear Information System (INIS)

    Ji, Jiayao; Li, Qinggang; Xie, Yuansheng; Zhang, Xueguang; Cui, Shaoyuan; Shi, Suozhu; Chen, Xiangmei

    2012-01-01

    Highlights: ► Overexpression of Robo2 caused reduced UB branching and glomerular number. ► Fewer MM cells surrounding the UB after overexpression of Robo2 in vitro. ► No abnormal Epithelial Morphology of UB or apoptosis of mm cells in the kidney. ► Overexpression of Robo2 affected MM cells migration and caused UB deficit. ► The reduced glomerular number can also be caused by fewer MM cells. -- Abstract: Roundabout 2 (Robo2) is a member of the membrane protein receptor family. The chemorepulsive effect of Slit2–Robo2 signaling plays vital roles in nervous system development and neuron migration. Slit2–Robo2 signaling is also important for maintaining the normal morphogenesis of the kidney and urinary collecting system, especially for the branching of the ureteric bud (UB) at the proper site. Slit2 or Robo2 mouse mutants exhibit multilobular kidneys, multiple ureters, and dilatation of the ureter, renal pelvis, and collecting duct system, which lead to vesicoureteral reflux. To understand the effect of Robo2 on kidney development, we used microinjection and electroporation to overexpress GFP-Robo2 in an in vitro embryonic kidney model. Our results show reduced UB branching and decreased glomerular number after in vitro Robo2 overexpression in the embryonic kidneys. We found fewer metanephric mesenchymal (MM) cells surrounding the UB but no abnormal morphology in the branching epithelial UB. Meanwhile, no significant change in MM proliferation or apoptosis was observed. These findings indicate that Robo2 is involved in the development of embryonic kidneys and that the normal expression of Robo2 can help maintain proper UB branching and glomerular morphogenesis. Overexpression of Robo2 leads to reduced UB branching caused by fewer surrounding MM cells, but MM cell apoptosis is not involved in this effect. Our study demonstrates that overexpression of Robo2 by microinjection in embryonic kidneys is an effective approach to study the function of Robo2.

  7. Rho-associated kinase activity is required for proper morphogenesis of the inner cell mass in the mouse blastocyst.

    Science.gov (United States)

    Laeno, Arlene May A; Tamashiro, Dana Ann A; Alarcon, Vernadeth B

    2013-11-01

    The blastocyst consists of the outer layer of trophectoderm and pluripotent inner cell mass (ICM), the precursor of the placenta and fetus, respectively. During blastocyst expansion, the ICM adopts a compact, ovoidal shape, whose proper morphology is crucial for normal embryogenesis. Rho-associated kinase (ROCK), an effector of small GTPase RHO signaling, mediates the diverse cellular processes of morphogenesis, but its role in ICM morphogenesis is unclear. Here, we demonstrate that ROCK is required for cohesion of ICM cells and formation of segregated tissues called primitive endoderm (PrE) and epiblast (Epi) in the ICM of the mouse blastocyst. Blastocyst treatment with ROCK inhibitors Y-27632 and Fasudil caused widening or spreading of the ICM, and intermingling of PrE and Epi. Widening of ICM was independent of trophectoderm because isolated ICMs as well as colonies of mouse embryonic stem cells (mESC) also spread upon Y-27632 treatment. PrE, Epi, and trophectoderm cell numbers were similar between control and treated blastocysts, suggesting that ROCK inhibition affected ICM morphology but not lineage differentiation. Rock1 and Rock2 knockdown via RNA interference in mESC also induced spreading, supporting the conclusion that morphological defects caused by the pharmacological inhibitors were due to ROCK inactivation. When blastocysts were transferred into surrogates, implantation efficiencies were unaffected by ROCK inhibition, but treated blastocysts yielded greater fetal loss. These results show that proper ICM morphology is dependent on ROCK activity and is crucial for fetal development. Our studies have wider implication for improving efficiencies of human assisted reproductive technologies that diminish pregnancy loss and promote successful births.

  8. A C-terminal, cysteine-rich site in poliovirus 2C(ATPase) is required for morphogenesis.

    Science.gov (United States)

    Wang, Chunling; Ma, Hsin-Chieh; Wimmer, Eckard; Jiang, Ping; Paul, Aniko V

    2014-06-01

    The morphogenesis of viruses belonging to the genus Enterovirus in the family Picornaviridae is still poorly understood despite decades-long investigations. However, we recently provided evidence that 2C(ATPase) gives specificity to poliovirus encapsidation through an interaction with capsid protein VP3. The polypeptide 2C(ATPase) is a highly conserved non-structural protein of enteroviruses with important roles in RNA replication, encapsidation and uncoating. We have identified a site (K279/R280) near the C terminus of the polypeptide that is required for morphogenesis. The aim of the current project was to search for additional functional sites near the C terminus of the 2C(ATPase) polypeptide, with particular interest in those that are required for encapsidation. We selected for analysis a cysteine-rich site of the polypeptide and constructed four mutants in which cysteines or a histidine was changed to an alanine. The RNA transcripts were transfected into HeLa cells yielding two lethal, one temperature-sensitive and one quasi-infectious mutants. All four mutants exhibited normal protein translation in vitro and three of them possessed severe RNA replication defects. The quasi-infectious mutant (C286A) yielded variants with a pseudo-reversion at the original site (A286D), but some also contained one additional mutation: A138V or M293V. The temperature-sensitive mutant (C272A/H273A) exhibited an encapsidation and possibly also an uncoating defect at 37 °C. Variants of this mutant revealed suppressor mutations at three different sites in the 2C(ATPase) polypeptide: A138V, M293V and K295R. We concluded that the cysteine-rich site near the C terminus of 2C(ATPase) is involved in encapsidation, possibly through an interaction with an upstream segment located between boxes A and B of the nucleotide-binding domain. © 2014 The Authors.

  9. Concise review: can the intrinsic power of branching morphogenesis be used for engineering epithelial tissues and organs?

    Science.gov (United States)

    Nigam, Sanjay K

    2013-12-01

    Branching morphogenesis is critical to the development of organs such as kidney, lung, mammary gland, prostate, pancreas, and salivary gland. Essentially, an epithelial bud becomes an iterative tip-stalk generator (ITSG) able to form a tree of branching ducts and/or tubules. In different organs, branching morphogenesis is governed by similar sets of genes. Epithelial branching has been recapitulated in vitro (or ex vivo) using three-dimensional cell culture and partial organ culture systems, and several such systems relevant to kidney tissue engineering are discussed here. By adapting systems like these it may be possible to harness the power inherent in the ITSG program to propagate and engineer epithelial tissues and organs. It is also possible to conceive of a universal ITSG capable of propagation that may, by recombination with organ-specific mesenchymal cells, be used for engineering many organ-like tissues similar to the organ from which the mesenchyme cells were derived, or toward which they are differentiated (from stem cells). The three-dimensional (3D) branched epithelial structure could act as a dynamic branching cellular scaffold to establish the architecture for the rest of the tissue. Another strategy-that of recombining propagated organ-specific ITSGs in 3D culture with undifferentiated mesenchymal stem cells-is also worth exploring. If feasible, such engineered tissues may be useful for the ex vivo study of drug toxicity, developmental biology, and physiology in the laboratory. Over the long term, they have potential clinical applications in the general fields of transplantation, regenerative medicine, and bioartificial medical devices to aid in the treatment of chronic kidney disease, diabetes, and other diseases.

  10. Role of cranial neural crest cells in visceral arch muscle positioning and morphogenesis in the Mexican axolotl, Ambystoma mexicanum.

    Science.gov (United States)

    Ericsson, Rolf; Cerny, Robert; Falck, Pierre; Olsson, Lennart

    2004-10-01

    The role of cranial neural crest cells in the formation of visceral arch musculature was investigated in the Mexican axolotl, Ambystoma mexicanum. DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine, perchlorate) labeling and green fluorescent protein (GFP) mRNA injections combined with unilateral transplantations of neural folds showed that neural crest cells contribute to the connective tissues but not the myofibers of developing visceral arch muscles in the mandibular, hyoid, and branchial arches. Extirpations of individual cranial neural crest streams demonstrated that neural crest cells are necessary for correct morphogenesis of visceral arch muscles. These do, however, initially develop in their proper positions also in the absence of cranial neural crest. Visceral arch muscles forming in the absence of neural crest cells start to differentiate at their origins but fail to extend toward their insertions and may have a frayed appearance. Our data indicate that visceral arch muscle positioning is controlled by factors that do not have a neural crest origin. We suggest that the cranial neural crest-derived connective tissues provide directional guidance important for the proper extension of the cranial muscles and the subsequent attachment to the insertion on the correct cartilage. In a comparative context, our data from the Mexican axolotl support the view that the cranial neural crest plays a fundamental role in the development of not only the skeleton of the vertebrate head but also in the morphogenesis of the cranial muscles and that this might be a primitive feature of cranial development in vertebrates. 2004 Wiley-Liss, Inc.

  11. A generic individual-based model to simulate morphogenesis, C-N acquisition and population dynamics in contrasting forage legumes.

    Science.gov (United States)

    Louarn, Gaëtan; Faverjon, Lucas

    2018-04-18

    Individual-based models (IBMs) are promising tools to disentangle plant interactions in multi-species grasslands and foster innovative species mixtures. This study describes an IBM dealing with the morphogenesis, growth and C-N acquisition of forage legumes that integrates plastic responses from functional-structural plant models. A generic model was developed to account for herbaceous legume species with contrasting above- and below-ground morphogenetic syndromes and to integrate the responses of plants to light, water and N. Through coupling with a radiative transfer model and a three-dimensional virtual soil, the model allows dynamic resolution of competition for multiple resources at individual plant level within a plant community. The behaviour of the model was assessed on a range of monospecific stands grown along gradients of light, water and N availability. The model proved able to capture the diversity of morphologies encountered among the forage legumes. The main density-dependent features known about even-age plant populations were correctly anticipated. The model predicted (1) the 'reciprocal yield' law relating average plant mass to density, (2) a self-thinning pattern close to that measured for herbaceous species and (3) consistent changes in the size structure of plant populations with time and pedo-climatic conditions. In addition, plastic changes in the partitioning of dry matter, the N acquisition mode and in the architecture of shoots and roots emerged from the integration of plant responses to their local environment. This resulted in taller plants and thinner roots when competition was dominated by light, and shorter plants with relatively more developed root systems when competition was dominated by soil resources. A population dynamic model considering growth and morphogenesis responses to multiple resources heterogeneously distributed in the environment was presented. It should allow scaling plant-plant interactions from individual to

  12. A novel role for MAPKAPK2 in morphogenesis during zebrafish development.

    Directory of Open Access Journals (Sweden)

    Beth A Holloway

    2009-03-01

    Full Text Available One of the earliest morphogenetic processes in the development of many animals is epiboly. In the zebrafish, epiboly ensues when the animally localized blastoderm cells spread, thin over, and enclose the vegetally localized yolk. Only a few factors are known to function in this fundamental process. We identified a maternal-effect mutant, betty boop (bbp, which displays a novel defect in epiboly, wherein the blastoderm margin constricts dramatically, precisely when half of the yolk cell is covered by the blastoderm, causing the yolk cell to burst. Whole-blastoderm transplants and mRNA microinjection rescue demonstrate that Bbp functions in the yolk cell to regulate epiboly. We positionally cloned the maternal-effect bbp mutant gene and identified it as the zebrafish homolog of the serine-threonine kinase Mitogen Activated Protein Kinase Activated Protein Kinase 2, or MAPKAPK2, which was not previously known to function in embryonic development. We show that the regulation of MAPKAPK2 is conserved and p38 MAP kinase functions upstream of MAPKAPK2 in regulating epiboly in the zebrafish embryo. Dramatic alterations in calcium dynamics, together with the massive marginal constrictive force observed in bbp mutants, indicate precocious constriction of an F-actin network within the yolk cell, which first forms at 50% epiboly and regulates epiboly progression. We show that MAPKAPK2 activity and its regulator p38 MAPK function in the yolk cell to regulate the process of epiboly, identifying a new pathway regulating this cell movement process. We postulate that a p38 MAPKAPK2 kinase cascade modulates the activity of F-actin at the yolk cell margin circumference allowing the gradual closure of the blastopore as epiboly progresses.

  13. A dioxin-like compound induces hyperplasia and branching morphogenesis in mouse mammary gland, through alterations in TGF-β1 and aryl hydrocarbon receptor signaling.

    Science.gov (United States)

    Miret, Noelia; Rico-Leo, Eva; Pontillo, Carolina; Zotta, Elsa; Fernández-Salguero, Pedro; Randi, Andrea

    2017-11-01

    Hexachlorobenzene (HCB) is a widespread environmental pollutant and a dioxin-like compound that binds weakly to the aryl hydrocarbon receptor (AhR). Because AhR and transforming growth factor β1 (TGF-β1) converge to regulate common signaling pathways, alterations in this crosstalk might contribute to developing preneoplastic lesions. The aim of this study was to evaluate HCB action on TGF-β1 and AhR signaling in mouse mammary gland, through AhR+/+ and AhR-/- models. Results showed a differential effect in mouse mammary epithelial cells (NMuMG), depending on the dose: 0.05μM HCB induced cell migration and TGF-β1 signaling, whereas 5μM HCB reduced cell migration, promoted cell cycle arrest and stimulated the dioxin response element (DRE) -dependent pathway. HCB (5μM) enhanced α-smooth muscle actin expression and decreased TGF-β receptor II mRNA levels in immortalized mouse mammary fibroblasts AhR+/+, resembling the phenotype of transformed cells. Accordingly, their conditioned medium was able to enhance NMuMG cell migration. Assays in C57/Bl6 mice showed HCB (3mg/kg body weight) to enhance ductal hyperplasia, cell proliferation, estrogen receptor α nuclear localization, branch density, and the number of terminal end buds in mammary gland from AhR+/+ mice. Primary culture of mammary epithelial cells from AhR+/+ mice showed reduced AhR mRNA levels after HCB exposure (0.05 and 5μM). Interestingly, AhR-/- mice exhibited an increase in ductal hyperplasia and mammary growth in the absence of HCB treatment, thus revealing the importance of AhR in mammary development. Our findings show that environmental HCB concentrations modulate AhR and TGF-β1 signaling, which could contribute to altered mammary branching morphogenesis, likely leading to preneoplastic lesions and retaining terminal end buds. Copyright © 2017. Published by Elsevier Inc.

  14. RAB-10 Regulates Dendritic Branching by Balancing Dendritic Transport

    Science.gov (United States)

    Taylor, Caitlin A.; Yan, Jing; Howell, Audrey S.; Dong, Xintong; Shen, Kang

    2015-01-01

    The construction of a large dendritic arbor requires robust growth and the precise delivery of membrane and protein cargoes to specific subcellular regions of the developing dendrite. How the microtubule-based vesicular trafficking and sorting systems are regulated to distribute these dendritic development factors throughout the dendrite is not well understood. Here we identify the small GTPase RAB-10 and the exocyst complex as critical regulators of dendrite morphogenesis and patterning in the C. elegans sensory neuron PVD. In rab-10 mutants, PVD dendritic branches are reduced in the posterior region of the cell but are excessive in the distal anterior region of the cell. We also demonstrate that the dendritic branch distribution within PVD depends on the balance between the molecular motors kinesin-1/UNC-116 and dynein, and we propose that RAB-10 regulates dendrite morphology by balancing the activity of these motors to appropriately distribute branching factors, including the transmembrane receptor DMA-1. PMID:26633194

  15. Regulating the Regulator

    Energy Technology Data Exchange (ETDEWEB)

    1992-08-26

    The article reports on a challenge to the UK electricity regulator to defend his record by the Coalition for Fair Electricity Regulation (COFFER). The challenge centres on whether the obligation for the regional electric companies (REC) to purchase power from the cheapest source is being enforced. This is related to the wider issue of whether the REC's support of combined-cycle gas turbine (CCGT) is economic. COFFER considers that uneconomic gas-fired power plants are being allowed to displace economic coal-fired stations. Aspects discussed include the background to the dispute and the costs of CCGT and coal fired power generation. 1 fig., 1 tab.

  16. Role of TGF-beta1-independent changes in protein neosynthesis, p38alphaMAPK, and cdc42 in hydrogen peroxide-induced senescence-like morphogenesis

    DEFF Research Database (Denmark)

    Chrétien, Aline; Dierick, Jean-François; Delaive, Edouard

    2008-01-01

    for p38(MAPK) activation, in turn triggering phosphorylation of L-caldesmon and HSP27. Cdc42 was also shown to be mainly responsible for the increase in TGF-beta1 mRNA level observed at 24 h after treatment with H(2)O(2) and onward. This study further clarified the mechanisms of senescence......The role of TGF-beta1 in hydrogen peroxide-induced senescence-like morphogenesis has been described. The aim of this work was to investigate whether TGF-beta1-independent changes in protein synthesis are involved in this morphogenesis and to study possible mechanisms occurring earlier than TGF-beta......1 overexpression. Among the multiple TGF-beta1-independent changes in protein neosynthesis, followed or not by posttranslational modifications, identified by proteomic analysis herein, those of ezrin, L-caldesmon, and HSP27 were particularly studied. Rho-GTPase cdc42 was shown to be responsible...

  17. Ultrastructural analysis of volutin-acidocalciumosomes formation in some species of bacteria, spirochetes, yeast and protozoa during morphogenesis and under environment different factors action

    International Nuclear Information System (INIS)

    Hovnanyan, K.O.; Hovnanyan, M.K.; Navasardyan, L.A.; Trchounian, A.A.

    2012-01-01

    Ultrastructure organization of volutin granules in some species of bacteria, spirochetes, yeast and protozoa cellular architecture was studied during morphogenesis and under environment different factors action leading to pathological changes. As the result of complex electron microscopic studies of morphogenesis in some species of prokaryotes and eukaryotic organisms the formation of new structures of volutin-acidocal-ciumosomes has been established within cell cytoplasm. In addition, under the ionizing roentgen and irradiation as well as some antibiotics action morphometric changes and changes in optical properties were also shown. Electron microscopic identification of volutin granules changes in structural organization in bacteria, spirochetes, yeast and protozoa might serve as appropriate express-method for visual evaluation of damage and reparation processes during environment

  18. Tooth Morphogenesis and FGF4 Expression During Development of Molar Tooth in Three Muroid Rodents: Calomyscus elburzensis (Calomyscidae), Mesocricetus auratus (Cricetidae) and Mus musculus (Muridae).

    Science.gov (United States)

    Hamidi, Kordiyeh; Darvish, Jamshid; Matin, Maryam M; Javanmard, Athar Sadat; Kilpatrick, C William

    2017-12-01

    To date, no studies have examined the tooth formation during developmental stages of brush-tailed mice (Calomyscidae) and true hamsters (Cricetidae). Herein, we compared the timing of tooth morphogenesis and FGF4 expression pattern during development of the first lower molar in Goodwin's brush-tailed mouse, Calomyscus elburzensis with two other muroid rodents; the house mouse, Mus musculus (Muridae), model organism for tooth morphogenesis, and the golden hamster, Mesocricetus auratus which shares great similarities in cusp pattern with brush-tailed mice. All three species were bred in captivity and developing embryos were isolated at different embryonic days (E). Histological evaluation of lower molars was performed and spatiotemporal pattern of FGF4 expression was determined by immunohistochemistry. Results indicated that morphogenesis of the tooth cusps starts at the beginning of the cap stage of the first lower molar (E14 in house mouse, about E11.5 in golden hamster and E22 in Goodwin's brush-tailed mouse). During the cap to bell stage (E15 in house mouse, E12 in golden hamster and at about E24 in Goodwin's brush-tailed mouse), a decrease in the expression of FGF4 was observed in the mesenchyme, except for the cusp tips. According to our observations, the developmental process of the first lower molar formation in Goodwin's brush-tailed mouse began much later as compared with the other two species. Despite the differences in the temporal pattern of molar development between these three members of the same superfamily (Muroidea), the correlation in the expression of FGF4 with specific stages of tooth morphogenesis supported its regulatory function. Anat Rec, 300:2138-2149, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  19. Caenorhabditis elegans Histone Deacetylase hda-1 Is Required for Morphogenesis of the Vulva and LIN-12/Notch-Mediated Specification of Uterine Cell Fates

    OpenAIRE

    Ranawade, Ayush Vasant; Cumbo, Philip; Gupta, Bhagwati P.

    2013-01-01

    Chromatin modification genes play crucial roles in development and disease. In Caenorhabditis elegans, the class I histone deacetylase family member hda-1 , a component of the nucleosome remodeling and deacetylation complex, has been shown to control cell proliferation. We recovered hda-1 in an RNA interference screen for genes involved in the morphogenesis of the egg-laying system. We found that hda-1 mutants have abnormal vulva morphology and vulval-uterine connections (i.e., no uterine-sea...

  20. Targeted overexpression of EZH2 in the mammary gland disrupts ductal morphogenesis and causes epithelial hyperplasia.

    Science.gov (United States)

    Li, Xin; Gonzalez, Maria E; Toy, Katherine; Filzen, Tracey; Merajver, Sofia D; Kleer, Celina G

    2009-09-01

    The Polycomb group protein enhancer of zeste homolog 2 (EZH2), which has roles during development of numerous tissues, is a critical regulator of cell type identity. Overexpression of EZH2 has been detected in invasive breast carcinoma tissue samples and is observed in human breast tissue samples of morphologically normal lobules up to 12 years before the development of breast cancer. The function of EZH2 during preneoplastic progression in the mammary gland is unknown. To investigate the role of EZH2 in the mammary gland, we targeted the expression of EZH2 to mammary epithelial cells using the mouse mammary tumor virus long terminal repeat. EZH2 overexpression resulted in aberrant terminal end bud architecture. By the age of 4 months, 100% of female mouse mammary tumor virus-EZH2 virgin mice developed intraductal epithelial hyperplasia resembling the human counterpart accompanied by premature differentiation of ductal epithelial cells and up-regulation of the luminal marker GATA-3. In additio