Notochord Morphogenesis in Mice: Current Understanding & Open Questions

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

2016-01-01

The notochord is the structure which defines chordates. 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...

A novel mammal-specific three partite enhancer element regulates node and notochord-specific Noto expression.

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Leonie Alten

Full Text Available The vertebrate organizer and notochord have conserved, essential functions for embryonic development and patterning. The restricted expression of developmental regulators in these tissues is directed by specific cis-regulatory modules (CRMs whose sequence conservation varies considerably. Some CRMs have been conserved throughout vertebrates and likely represent ancestral regulatory networks, while others have diverged beyond recognition but still function over a wide evolutionary range. Here we identify and characterize a mammalian-specific CRM required for node and notochord specific (NNC expression of NOTO, a transcription factor essential for node morphogenesis, nodal cilia movement and establishment of laterality in mouse. A 523 bp enhancer region (NOCE upstream the Noto promoter was necessary and sufficient for NNC expression from the endogenous Noto locus. Three subregions in NOCE together mediated full activity in vivo. Binding sites for known transcription factors in NOCE were functional in vitro but dispensable for NOCE activity in vivo. A FOXA2 site in combination with a novel motif was necessary for NOCE activity in vivo. Strikingly, syntenic regions in non-mammalian vertebrates showed no recognizable sequence similarities. In contrast to its activity in mouse NOCE did not drive NNC expression in transgenic fish. NOCE represents a novel, mammal-specific CRM required for the highly restricted Noto expression in the node and nascent notochord and thus regulates normal node development and function.

A novel mammal-specific three partite enhancer element regulates node and notochord-specific Noto expression.

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Alten, Leonie; Schuster-Gossler, Karin; Eichenlaub, Michael P; Wittbrodt, Beate; Wittbrodt, Joachim; Gossler, Achim

2012-01-01

The vertebrate organizer and notochord have conserved, essential functions for embryonic development and patterning. The restricted expression of developmental regulators in these tissues is directed by specific cis-regulatory modules (CRMs) whose sequence conservation varies considerably. Some CRMs have been conserved throughout vertebrates and likely represent ancestral regulatory networks, while others have diverged beyond recognition but still function over a wide evolutionary range. Here we identify and characterize a mammalian-specific CRM required for node and notochord specific (NNC) expression of NOTO, a transcription factor essential for node morphogenesis, nodal cilia movement and establishment of laterality in mouse. A 523 bp enhancer region (NOCE) upstream the Noto promoter was necessary and sufficient for NNC expression from the endogenous Noto locus. Three subregions in NOCE together mediated full activity in vivo. Binding sites for known transcription factors in NOCE were functional in vitro but dispensable for NOCE activity in vivo. A FOXA2 site in combination with a novel motif was necessary for NOCE activity in vivo. Strikingly, syntenic regions in non-mammalian vertebrates showed no recognizable sequence similarities. In contrast to its activity in mouse NOCE did not drive NNC expression in transgenic fish. NOCE represents a novel, mammal-specific CRM required for the highly restricted Noto expression in the node and nascent notochord and thus regulates normal node development and function.

Distinguishing benign notochordal cell tumors from vertebral chordoma

International Nuclear Information System (INIS)

Yamaguchi, Takehiko; Iwata, Jun; Sugihara, Shinsuke; McCarthy, Edward F.; Karita, Michiaki; Murakami, Hideki; Kawahara, Norio; Tsuchiya, Hiroyuki; Tomita, Katsuro

2008-01-01

The objective was to characterize imaging findings of benign notochordal cell tumors (BNCTs). Clinical and imaging data for 9 benign notochordal cell tumors in 7 patients were reviewed retrospectively. Conventional radiographs (n = 9), bone scintigrams (n = 2), computed tomographic images (n = 7), and magnetic resonance images (n = 8) were reviewed. Eight of the 9 lesions were stained with hematoxylin-eosin and microscopically examined. There were 3 male and 4 female patients with an age range of 22 to 55 years (average age, 44 years). Two patients had two lesions at different sites. The lesions involved the cervical spine in 4 patients, the lumbar spine in 2, the sacrum in 2, and the coccyx in 1. The most common symptom was mild pain. The lesions of 2 patients were found incidentally during imaging studies for unrelated conditions. Five patients underwent surgical procedures. One patient died of surgical complications. All other patients have been well without recurrent or progressive disease for 13 to 84 months. Radiographs usually did not reveal significant abnormality. Five lesions exhibited subtle sclerosis and 1 showed intense sclerosis. Technetium bone scan did not reveal any abnormal uptake. Computed tomography images had increased density within the vertebral bodies. The lesions had a homogeneous low signal intensity on T1-weighted magnetic resonance images and a high intensity on T2-weighted images without soft-tissue mass. Microscopically, lesions contained sheets of adipocyte-like vacuolated chordoid cells without a myxoid matrix. Benign notochordal cell tumors may be found during routine clinical examinations and do not require surgical management unless they show extraosseous disease. These tumors should be recognized by radiologists, pathologists, and orthopedic surgeons to prevent operations, which usually are extensive. (orig.)

Stochasticity and stereotypy in the Ciona notochord.

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Carlson, Maia; Reeves, Wendy; Veeman, Michael

2015-01-15

Fate mapping with single cell resolution has typically been confined to embryos with completely stereotyped development. The lineages giving rise to the 40 cells of the Ciona notochord are invariant, but the intercalation of those cells into a single-file column is not. Here we use genetic labeling methods to fate map the Ciona notochord with both high resolution and large sample sizes. We find that the ordering of notochord cells into a single column is not random, but instead shows a distinctive signature characteristic of mediolaterally-biased intercalation. We find that patterns of cell intercalation in the notochord are somewhat stochastic but far more stereotyped than previously believed. Cell behaviors vary by lineage, with the secondary notochord lineage being much more constrained than the primary lineage. Within the primary lineage, patterns of intercalation reflect the geometry of the intercalating tissue. We identify the latest point at which notochord morphogenesis is largely stereotyped, which is shortly before the onset of mediolateral intercalation and immediately after the final cell divisions in the primary lineage. These divisions are consistently oriented along the AP axis. Our results indicate that the interplay between stereotyped and stochastic cell behaviors in morphogenesis can only be assessed by fate mapping experiments that have both cellular resolution and large sample sizes. Copyright © 2014 Elsevier Inc. All rights reserved.

Ciona intestinalis notochord as a new model to investigate the cellular and molecular mechanisms of tubulogenesis.

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Denker, Elsa; Jiang, Di

2012-05-01

Biological tubes are a prevalent structural design across living organisms. They provide essential functions during the development and adult life of an organism. Increasing progress has been made recently in delineating the cellular and molecular mechanisms underlying tubulogenesis. This review aims to introduce ascidian notochord morphogenesis as an interesting model system to study the cell biology of tube formation, to a wider cell and developmental biology community. We present fundamental morphological and cellular events involved in notochord morphogenesis, compare and contrast them with other more established tubulogenesis model systems, and point out some unique features, including bipolarity of the notochord cells, and using cell shape changes and cell rearrangement to connect lumens. We highlight some initial findings in the molecular mechanisms of notochord morphogenesis. Based on these findings, we present intriguing problems and put forth hypotheses that can be addressed in future studies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sonic hedgehog in the notochord is sufficient for patterning of the intervertebral discs.

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Choi, Kyung-Suk; Lee, Chanmi; Harfe, Brian D

2012-01-01

The intervertebral discs, located between adjacent vertebrae, are required for stability of the spine and distributing mechanical load throughout the vertebral column. All cell types located in the middle regions of the discs, called nuclei pulposi, are derived from the embryonic notochord. Recently, it was shown that the hedgehog signaling pathway plays an essential role during formation of nuclei pulposi. However, during the time that nuclei pulposi are forming, Shh is expressed in both the notochord and the nearby floor plate. To determine the source of SHH protein sufficient for formation of nuclei pulposi we removed Shh from either the floor plate or the notochord using tamoxifen-inducible Cre alleles. Removal of Shh from the floor plate resulted in phenotypically normal intervertebral discs, indicating that Shh expression in this tissue is not required for disc patterning. In addition, embryos that lacked Shh in the floor plate had normal vertebral columns, demonstrating that Shh expression in the notochord is sufficient for pattering the entire vertebral column. Removal of Shh from the notochord resulted in the absence of Shh in the floor plate, loss of intervertebral discs and vertebral structures. These data indicate that Shh expression in the notochord is sufficient for patterning of the intervertebral discs and the vertebral column. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Emilin3 is required for notochord sheath integrity and interacts with Scube2 to regulate notochord-derived Hedgehog signals.

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Corallo, Diana; Schiavinato, Alvise; Trapani, Valeria; Moro, Enrico; Argenton, Francesco; Bonaldo, Paolo

2013-11-01

The notochord is a transient and essential structure that provides both mechanical and signaling cues to the developing vertebrate embryo. In teleosts, the notochord is composed of a core of large vacuolated cells and an outer layer of cells that secrete the notochord sheath. In this work, we have identified the extracellular matrix glycoprotein Emilin3 as a novel essential component of the zebrafish notochord sheath. The development of the notochord sheath is impaired in Emilin3 knockdown embryos. The patterning activity of the notochord is also affected by Emilin3, as revealed by the increase of Hedgehog (Hh) signaling in Emilin3-depleted embryos and the decreased Hh signaling in embryos overexpressing Emilin3 in the notochord. In vitro and in vivo experiments indicate that Emilin3 modulates the availability of Hh ligands by interacting with the permissive factor Scube2 in the notochord sheath. Overall, this study reveals a new role for an EMILIN protein and reinforces the concept that structure and function of the notochord are strictly linked.

Anterior-posterior regionalized gene expression in the Ciona notochord.

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Reeves, Wendy; Thayer, Rachel; Veeman, Michael

2014-04-01

In the simple ascidian chordate Ciona, the signaling pathways and gene regulatory networks giving rise to initial notochord induction are largely understood and the mechanisms of notochord morphogenesis are being systematically elucidated. The notochord has generally been thought of as a non-compartmentalized or regionalized organ that is not finely patterned at the level of gene expression. Quantitative imaging methods have recently shown, however, that notochord cell size, shape, and behavior vary consistently along the anterior-posterior (AP) axis. Here we screen candidate genes by whole mount in situ hybridization for potential AP asymmetry. We identify 4 genes that show non-uniform expression in the notochord. Ezrin/radixin/moesin (ERM) is expressed more strongly in the secondary notochord lineage than the primary. CTGF is expressed stochastically in a subset of notochord cells. A novel calmodulin-like gene (BCamL) is expressed more strongly at both the anterior and posterior tips of the notochord. A TGF-β ortholog is expressed in a gradient from posterior to anterior. The asymmetries in ERM, BCamL, and TGF-β expression are evident even before the notochord cells have intercalated into a single-file column. We conclude that the Ciona notochord is not a homogeneous tissue but instead shows distinct patterns of regionalized gene expression. Copyright © 2013 Wiley Periodicals, Inc.

Spine Patterning Is Guided by Segmentation of the Notochord Sheath

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Wopat, Susan; Bagwell, Jennifer; Sumigray, Kaelyn D.; Dickson, Amy L.; Huitema, Leonie F.A.; Poss, Kenneth D.; Schulte-Merker, Stefan; Bagnat, Michel

2018-01-01

The spine is a segmented axial structure made of alternating vertebral bodies (centra) and intervertebral discs (IVDs) assembled around the notochord. Here, we show that, prior to centra formation, the outer epithelial cell layer of the zebrafish notochord, the sheath, segments into alternating

Mineralization of the vertebral bodies in Atlantic salmon (Salmo salar L.) is initiated segmentally in the form of hydroxyapatite crystal accretions in the notochord sheath.

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Wang, Shou; Kryvi, Harald; Grotmol, Sindre; Wargelius, Anna; Krossøy, Christel; Epple, Mattias; Neues, Frank; Furmanek, Tomasz; Totland, Geir K

2013-08-01

We performed a sequential morphological and molecular biological study of the development of the vertebral bodies in Atlantic salmon (Salmo salar L.). Mineralization starts in separate bony elements which fuse to form complete segmental rings within the notochord sheath. The nucleation and growth of hydroxyapatite crystals in both the lamellar type II collagen matrix of the notochord sheath and the lamellar type I collagen matrix derived from the sclerotome, were highly similar. In both matrices the hydroxyapatite crystals nucleate and accrete on the surface of the collagen fibrils rather than inside the fibrils, a process that may be controlled by a template imposed by the collagen fibrils. Apatite crystal growth starts with the formation of small plate-like structures, about 5 nm thick, that gradually grow and aggregate to form extensive multi-branched crystal arborizations, resembling dendritic growth. The hydroxyapatite crystals are always oriented parallel to the long axis of the collagen fibrils, and the lamellar collagen matrices provide oriented support for crystal growth. We demonstrate here for the first time by means of synchroton radiation based on X-ray diffraction that the chordacentra contain hydroxyapatite. We employed quantitative real-time PCR to study the expression of key signalling molecule transcripts expressed in the cellular core of the notochord. The results indicate that the notochord not only produces and maintains the notochord sheath but also expresses factors known to regulate skeletogenesis: sonic hedgehog (shh), indian hedgehog homolog b (ihhb), parathyroid hormone 1 receptor (pth1r) and transforming growth factor beta 1 (tgfb1). In conclusion, our study provides evidence for the process of vertebral body development in teleost fishes, which is initially orchestrated by the notochord. © 2013 Anatomical Society.

Notochord to Nucleus Pulposus Transition.

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Lawson, Lisa; Harfe, Brian D

2015-10-01

A tissue that commonly deteriorates in older vertebrates is the intervertebral disc, which is located between the vertebrae. Age-related changes in the intervertebral discs are thought to cause most cases of back pain. Back pain affects more than half of people over the age of 65, and the treatment of back pain costs 50-100 billion dollars per year in the USA. The normal intervertebral disc is composed of three distinct regions: a thick outer ring of fibrous cartilage called the annulus fibrosus, a gel-like material that is surrounded by the annulus fibrosus called the nucleus pulposus, and superior and inferior cartilaginous end plates. The nucleus pulposus has been shown to be critical for disc health and function. Damage to this structure often leads to disc disease. Recent reports have demonstrated that the embryonic notochord, a rod-like structure present in the midline of vertebrate embryos, gives rise to all cell types found in adult nuclei pulposi. The mechanism responsible for the transformation of the notochord into nuclei pulposi is unknown. In this review, we discuss potential molecular and physical mechanisms that may be responsible for the notochord to nuclei pulposi transition.

Notochord isolation using laser capture microdissection.

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Santegoeds, R G C; Yakkioui, Y; Jahanshahi, A; Raven, G; Van Overbeeke, J J; Herrler, A; Temel, Y

2017-03-01

Chordoma are malignant tumors of the axial skeleton, which arise from remnants of the notochord. The Notochord (chorda dorsalis) is an essential embryonic structure involved in the development of the nervous system and axial skeleton. Therefore, the notochord seems to be the most biologically relevant control tissue to study chordoma in molecular biology research. Nevertheless, up to now mainly different tissues but not the notochord have been used as control for chordoma, due to difficulty of isolating notochordal tissue. Here, we describe a fast and precise method of isolating notochordal cells. Examination of human fetuses, with a gestation of 9, 11 and 13 weeks, using (immuno)histochemical methods was performed. To isolate pure notochord cells for further molecular biology investigation five flash frozen fetuses between 9 and 10 weeks of gestation were dissected by microtome slicing. Thereafter pure notochord cells for further molecular biology investigation where harvested by using laser capture microdissection (LCM). RNA was extracted from these samples and used in quantitative PCR. This study illustrates notochord of embryonic spines in three different stages of gestation (9-11-13 weeks). Immunohistochemical staining with brachyury showed strong staining of the notochord, but also weak staining of the intervertebral disc and vertebral body. LCM of notochord slices and subsequent total RNA extraction resulted in a good yield of total RNA. qPCR analysis of two housekeeping genes confirmed the quality of the RNA. LCM is a fast and precise method to isolate notochord and the quality and yield RNA extracted from this tissue is sufficient for qPCR analysis. Therefore early embryo notochord isolated by LCM is suggested to be the gold standard for future research in chordoma development, classification and diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Stochastic model of cell rearrangements in convergent extension of ascidian notochord

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Lubkin, Sharon; Backes, Tracy; Latterman, Russell; Small, Stephen

2007-03-01

We present a discrete stochastic cell based model of convergent extension of the ascidian notochord. Our work derives from research that clarifies the coupling of invagination and convergent extension in ascidian notochord morphogenesis (Odell and Munro, 2002). We have tested the roles of cell-cell adhesion, cell-extracellular matrix adhesion, random motion, and extension of individual cells, as well as the presence or absence of various tissue types, and determined which factors are necessary and/or sufficient for convergent extension.

Evolution of the vertebrate claudin gene family: insights from a basal vertebrate, the sea lamprey.

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Mukendi, Christian; Dean, Nicholas; Lala, Rushil; Smith, Jeramiah; Bronner, Marianne E; Nikitina, Natalya V

2016-01-01

Claudins are major constituents of tight junctions, contributing both to their intercellular sealing and selective permeability properties. While claudins and claudin-like molecules are present in some invertebrates, the association of claudins with tight junctions has been conclusively documented only in vertebrates. Here we report the sequencing, phylogenetic analysis and comprehensive spatiotemporal expression analysis of the entire claudin gene family in the basal extant vertebrate, the sea lamprey. Our results demonstrate that clear orthologues to about half of all mammalian claudins are present in the lamprey, suggesting that at least one round of whole genome duplication contributed to the diversification of this gene family. Expression analysis revealed that claudins are expressed in discrete and specific domains, many of which represent vertebrate-specific innovations, such as in cranial ectodermal placodes and the neural crest; whereas others represent structures characteristic of chordates, e.g. pronephros, notochord, somites, endostyle and pharyngeal arches. By comparing the embryonic expression of claudins in the lamprey to that of other vertebrates, we found that ancestral expression patterns were often preserved in higher vertebrates. Morpholino mediated loss of Cldn3b demonstrated a functional role for this protein in placode and pharyngeal arch morphogenesis. Taken together, our data provide novel insights into the origins and evolution of the claudin gene family and the significance of claudin proteins in the evolution of vertebrates.

The floor plate is sufficient for development of the sclerotome and spine without the notochord.

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Ando, Takashi; Semba, Kei; Suda, Hiroko; Sei, Akira; Mizuta, Hiroshi; Araki, Masatake; Abe, Kuniya; Imai, Kenji; Nakagata, Naomi; Araki, Kimi; Yamamura, Ken-ichi

2011-01-01

Danforth'sshort-tail (Sd) mouse is a semi-dominant mutation affecting the development of the vertebral column. Although the notochord degenerates completely by embryonic day 9.5, the vertebral column exists up to the lumber region, suggesting that the floor plate can substitute for notochord function. We previously established the mutant mouse line, Skt(Gt), through gene trap mutagenesis and identified the novel gene, Skt, which was mapped 0.95cM distal to the Sd locus. Taking advantage of the fact that monitoring notochordal development and genotyping of the Sd locus can be performed using the Skt(Gt) allele, we assessed the development of the vertebra, notochord, somite, floor plate and sclerotome in +-+/+-Skt(Gt), Sd-+/+-+, Sd-Skt(Gt)/+-+, Sd-Skt(Gt)/+-Skt(Gt), Sd-+/Sd-+ and Sd-Skt(Gt)/Sd-Skt(Gt) embryos. In Sd homozygous mutants with a C57BL/6 genetic background, the vertebral column was truncated in the 6th thoracic vertebra, which was more severe than previously reported. The floor plate and sclerotome developed to the level of somite before notochord degeneration and the number of remaining vertebrae corresponded well with the level of development of the floor plate and sclerotome. Defects to the sclerotome and subsequent vertebral development were not due to failure of somitogenesis. Taken together, these results suggest that the notochord induced floor plate development before degeneration, and that the remaining floor plate is sufficient for maintenance of differentiation of the somite into the sclerotome and vertebra in the absence of the notochord. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs.

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Choi, Kyung-Suk; Harfe, Brian D

2011-06-07

The vertebrae notochord is a transient rod-like structure that produces secreted factors that are responsible for patterning surrounding tissues. During later mouse embryogenesis, the notochord gives rise to the middle part of the intervertebral disc, called the nucleus pulposus. Currently, very little is known about the molecular mechanisms responsible for forming the intervertebral discs. Here we demonstrate that hedgehog signaling is required for formation of the intervertebral discs. Removal of hedgehog signaling in the notochord and nearby floorplate resulted in the formation of an aberrant notochord sheath that normally surrounds this structure. In the absence of the notochord sheath, small nuclei pulposi were formed, with most notochord cells dispersed throughout the vertebral bodies during embryogenesis. Our data suggest that the formation of the notochord sheath requires hedgehog signaling and that the sheath is essential for maintaining the rod-like structure of the notochord during early embryonic development. As notochord cells form nuclei pulposi, we propose that the notochord sheath functions as a "wrapper" around the notochord to constrain these cells along the vertebral column.

FAS/FASL are dysregulated in chordoma and their loss-of-function impairs zebrafish notochord formation.

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Ferrari, Luca; Pistocchi, Anna; Libera, Laura; Boari, Nicola; Mortini, Pietro; Bellipanni, Gianfranco; Giordano, Antonio; Cotelli, Franco; Riva, Paola

2014-07-30

Chordoma is a rare malignant tumor that recapitulates the notochord phenotype and is thought to derive from notochord remnants not correctly regressed during development. Apoptosis is necessary for the proper notochord development in vertebrates, and the apoptotic pathway mediated by Fas and Fasl has been demonstrated to be involved in notochord cells regression. This study was conducted to investigate the expression of FAS/FASL pathway in a cohort of skull base chordomas and to analyze the role of fas/fasl homologs in zebrafish notochord formation. FAS/FASL expression was found to be dysregulated in chordoma leading to inactivation of the downstream Caspases in the samples analyzed. Both fas and fasl were specifically expressed in zebrafish notochord sorted cells. fas and fasl loss-of-function mainly resulted in larvae with notochord multi-cell-layer jumps organization, larger vacuolated notochord cells, defects in the peri-notochordal sheath structure and in vertebral mineralization. Interestingly, we observed the persistent expression of ntla and col2a1a, the zebrafish homologs of the human T gene and COL2A1 respectively, which are specifically up-regulated in chordoma. These results demonstrate for the first time the dysregulation of FAS/FASL in chordoma and their role in notochord formation in the zebrafish model, suggesting their possible implication in chordoma onset.

Development of the annelid axochord: insights into notochord evolution.

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Lauri, Antonella; Brunet, Thibaut; Handberg-Thorsager, Mette; Fischer, Antje H L; Simakov, Oleg; Steinmetz, Patrick R H; Tomer, Raju; Keller, Philipp J; Arendt, Detlev

2014-09-12

The origin of chordates has been debated for more than a century, with one key issue being the emergence of the notochord. In vertebrates, the notochord develops by convergence and extension of the chordamesoderm, a population of midline cells of unique molecular identity. We identify a population of mesodermal cells in a developing invertebrate, the marine annelid Platynereis dumerilii, that converges and extends toward the midline and expresses a notochord-specific combination of genes. These cells differentiate into a longitudinal muscle, the axochord, that is positioned between central nervous system and axial blood vessel and secretes a strong collagenous extracellular matrix. Ancestral state reconstruction suggests that contractile mesodermal midline cells existed in bilaterian ancestors. We propose that these cells, via vacuolization and stiffening, gave rise to the chordate notochord. Copyright © 2014, American Association for the Advancement of Science.

Egfl6 is involved in zebrafish notochord development.

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Wang, Xueqian; Wang, Xin; Yuan, Wei; Chai, Renjie; Liu, Dong

2015-08-01

The epidermal growth factor (EGF) repeat motif defines a superfamily of diverse protein involved in regulating a variety of cellular and physiological processes, such as cell cycle, cell adhesion, proliferation, migration, and neural development. Egfl6, an EGF protein, also named MAGE was first cloned in human tissue. Up to date, the study of zebrafish Egfl6 expression pattern and functional analysis of Egfl6 involved in embryonic development of vertebrate in vivo is thus far lacking. Here we reported that Egfl6 was involved in zebrafish notochord development. It was shown that Egfl6 mRNA was expressed in zebrafish, developing somites, fin epidermis, pharyngeal arches, and hindbrain region. Particularly the secreted Egfl6 protein was significantly accumulated in notochord. Loss of Egfl6 function in zebrafish embryos resulted in curved body with distorted notochord in the posterior trunk. It was observed that expression of all Notch ligand and receptors in notochord of 28 hpf Egfl6 morphants was not affected, except notch2, which was up-regulated. We found that inhibition of Notch signaling by DAPT efficiently rescued notochord developmental defect of Egfl6 deficiency embryos.

Identification of vimentin- and elastin-like transcripts specifically expressed in developing notochord of Atlantic salmon (Salmo salar L.).

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Sagstad, Anita; Grotmol, Sindre; Kryvi, Harald; Krossøy, Christel; Totland, Geir K; Malde, Ketil; Wang, Shou; Hansen, Tom; Wargelius, Anna

2011-11-01

The notochord functions as the midline structural element of all vertebrate embryos, and allows movement and growth at early developmental stages. Moreover, during embryonic development, notochord cells produce secreted factors that provide positional and fate information to a broad variety of cells within adjacent tissues, for instance those of the vertebrae, central nervous system and somites. Due to the large size of the embryo, the salmon notochord is useful to study as a model for exploring notochord development. To investigate factors that might be involved in notochord development, a normalized cDNA library was constructed from a mix of notochords from ∼500 to ∼800 day°. From the 1968 Sanger-sequenced transcripts, 22 genes were identified to be predominantly expressed in the notochord compared to other organs of salmon. Twelve of these genes were found to show expressional regulation around mineralization of the notochord sheath; 11 genes were up-regulated and one gene was down-regulated. Two genes were found to be specifically expressed in the notochord; these genes showed similarity to vimentin (acc. no GT297094) and elastin (acc. no GT297478). In-situ results showed that the vimentin- like transcript was expressed in both chordocytes and chordoblasts, whereas the elastin- like transcript was uniquely expressed in the chordoblasts lining the notochordal sheath. In salmon aquaculture, vertebral deformities are a common problem, and some malformations have been linked to the notochord. The expression of identified transcripts provides further insight into processes taking place in the developing notochord, prior to and during the early mineralization period.

Essential role for the alpha 1 chain of type VIII collagen in zebrafish notochord formation.

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Gansner, John M; Gitlin, Jonathan D

2008-12-01

Several zebrafish mutants identified in large-scale forward genetic screens exhibit notochord distortion. We now report the cloning and further characterization of one such mutant, gulliver(m208) (gul(m208)). The notochord defect in gul(m208) mutants is exacerbated under conditions of copper depletion or lysyl oxidase cuproenzyme inhibition that are without a notochord effect on wild-type embryos. The gul(m208) phenotype results from a missense mutation in the gene encoding Col8a1, a lysyl oxidase substrate, and morpholino knockdown of col8a1 recapitulates the notochord distortion observed in gul(m208) mutants. Of interest, the amino acid mutated in gul(m208) Col8a1 is highly conserved, and the equivalent substitution in a closely related human protein, COL10A1, causes Schmid metaphyseal chondrodysplasia. Taken together, the data identify a new protein essential for notochord morphogenesis, extend our understanding of gene-nutrient interactions in early development, and suggest that human mutations in COL8A1 may cause structural birth defects. (c) 2008 Wiley-Liss, Inc.

Histology and histochemistry of the gekkotan notochord and their bearing on the development of notochordal cartilage.

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Jonasson, Kristin A; Russell, Anthony P; Vickaryous, Matthew K

2012-06-01

The persistence of the notochord into the skeletally mature life stage is characteristic of gekkotans, but is otherwise of rare occurrence among amniotes. The taxonomic diversity of Gekkota affords the opportunity to investigate the structure and development of this phylogenetically ancestral component of the skeleton, and to determine its basic characteristics. The gekkotan notochord spans almost the entire postcranial long axis and is characterized by a moniliform morphology with regularly alternating zones of chordoid and chondroid tissue. Chordoid tissue persists in the region of intervertebral articulations and occupies the cavitations that lie between the centra of the amphicoelous vertebrae. Chondroid tissue is restricted to zones in which the diameter of the notochord is reduced, corresponding to mid-vertebral locations. In the tail, these zones of chondroid tissue are associated with the autotomic fracture planes. Chondroid tissue first manifests during late embryogenesis, appears to differentiate from pre-existing chordoid tissue, and has the histological and histochemical characteristics of cartilage. Our observations lend support to the hypothesis that cartilage can be derived directly from notochordal tissue, and suggest that the latter may be an evolutionary and developmental precursor to chordate cartilage. The persistence of chordoid tissue in the intervertebral regions of amphicoelous vertebrae is consistent with a suite of paedomorphic traits exhibited by gekkotans and suggests that the typical hydrostatic nature of notochordal tissue may play a role in mechanically governing patterns of displacement between adjacent amphicoelous vertebrae that lack extensive centrum-to-centrum contact. Copyright © 2012 Wiley Periodicals, Inc.

BMP antagonism by Noggin is required in presumptive notochord cells for mammalian foregut morphogenesis.

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Fausett, Sarah R; Brunet, Lisa J; Klingensmith, John

2014-07-01

Esophageal atresia with tracheoesophageal fistula (EA/TEF) is a serious human birth defect, in which the esophagus ends before reaching the stomach, and is aberrantly connected with the trachea. Several mouse models of EA/TEF have recently demonstrated that proper dorsal/ventral (D/V) patterning of the primitive anterior foregut endoderm is essential for correct compartmentalization of the trachea and esophagus. Here we elucidate the pathogenic mechanisms underlying the EA/TEF that occurs in mice lacking the BMP antagonist Noggin, which display correct dorsal/ventral patterning. To clarify the mechanism of this malformation, we use spatiotemporal manipulation of Noggin and BMP receptor 1A conditional alleles during foregut development. Surprisingly, we find that the expression of Noggin in the compartmentalizing endoderm is not required to generate distinct tracheal and esophageal tubes. Instead, we show that Noggin and BMP signaling attenuation are required in the early notochord to correctly resolve notochord cells from the dorsal foregut endoderm, which in turn, appears to be a prerequisite for foregut compartmentalization. Collectively, our findings support an emerging model for a mechanism underlying EA/TEF in which impaired notochord resolution from the early endoderm causes the foregut to be hypo-cellular just prior to the critical period of compartmentalization. Our further characterizations suggest that Noggin may regulate a cell rearrangement process that involves reciprocal E-cadherin and Zeb1 expression in the resolving notochord cells. Copyright © 2014. Published by Elsevier Inc.

Wnt5 is required for notochord cell intercalation in the ascidian Halocynthia roretzi.

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Niwano, Tomoko; Takatori, Naohito; Kumano, Gaku; Nishida, Hiroki

2009-08-25

In the embryos of various animals, the body elongates after gastrulation by morphogenetic movements involving convergent extension. The Wnt/PCP (planar cell polarity) pathway plays roles in this process, particularly mediolateral polarization and intercalation of the embryonic cells. In ascidians, several factors in this pathway, including Wnt5, have been identified and found to be involved in the intercalation process of notochord cells. In the present study, the role of the Wnt5 genes, Hr-Wnt5alpha (Halocynthia roretzi Wnt5alpha) and Hr-Wnt5beta, in convergent extension was investigated in the ascidian H. roretzi by injecting antisense oligonucleotides and mRNAs into single precursor blastomeres of various tissues, including notochord, at the 64-cell stage. Hr-Wnt5alpha is expressed in developing notochord and was essential for notochord morphogenesis. Precise quantitative control of its expression level was crucial for proper cell intercalation. Overexpression of Wnt5 proteins in notochord and other tissues that surround the notochord indicated that Wnt5alpha plays a role within the notochord, and is unlikely to be the source of polarizing cues arising outside the notochord. Detailed mosaic analysis of the behaviour of individual notochord cells overexpressing Wnt5alpha indicated that a Wnt5alpha-manipulated cell does not affect the behaviour of neighbouring notochord cells, suggesting that Wnt5alpha works in a cell-autonomous manner. This is further supported by comparison of the results of Wnt5alpha and Dsh (Dishevelled) knockdown experiments. In addition, our results suggest that the Wnt/PCP pathway is also involved in mediolateral intercalation of cells of the ventral row of the nerve cord (floor plate) and the endodermal strand. The present study highlights the role of the Wnt5alpha signal in notochord convergent extension movements in ascidian embryos. Our results raise the novel possibility that Wnt5alpha functions in a cell-autonomous manner in

The effect of adriamycin exposure on the notochord of mouse embryos.

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Hajduk, Piotr; May, Alison; Puri, Prem; Murphy, Paula

2012-04-01

The notochord has important structural and signaling properties during vertebrate development with key roles in patterning surrounding tissues, including the foregut. The adriamycin mouse model is an established model of foregut anomalies where exposure of embryos in utero to the drug adriamycin leads to malformations including oesophageal atresia and tracheoesophageal fistula. In addition to foregut abnormalities, treatment also causes branching, displacement, and hypertrophy of the notochord. Here, we explore the hypothesis that the notochord may be a primary target of disruption leading to abnormal patterning of the foregut by examining notochord position and structure in early embryos following adriamycin exposure. Treated (n = 46) and control (n = 30) embryos were examined during the crucial period when the notochord normally delaminates away from the foregut endoderm (6-28 somite pairs). Transverse sections were derived from the anterior foregut and analyzed by confocal microscopy following immunodetection of extracellular matrix markers E-cadherin and Laminin. In adriamycin-treated embryos across all stages, the notochord was abnormally displaced ventrally with prolonged attachment to the foregut endoderm. While E-cadherin was normally detected in the foregut endoderm with no expression in the notochord of control embryos, treated embryos up to 24 somites showed ectopic notochordal expression indicating a change in characteristics of the tissue; specifically an increase in intracellular adhesiveness, which may be instrumental in structural changes, affecting mechanical and signaling properties. This is consistent with disruption of the notochord leading to altered signaling to the foregut causing abnormal patterning and congenital foregut malformations. © 2012 Wiley Periodicals, Inc.

Structural requirements for PACSIN/Syndapin operation during zebrafish embryonic notochord development.

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Edeling, Melissa A; Sanker, Subramaniam; Shima, Takaki; Umasankar, P K; Höning, Stefan; Kim, Hye Y; Davidson, Lance A; Watkins, Simon C; Tsang, Michael; Owen, David J; Traub, Linton M

2009-12-03

PACSIN/Syndapin proteins are membrane-active scaffolds that participate in endocytosis. The structure of the Drosophila Syndapin N-terminal EFC domain reveals a crescent shaped antiparallel dimer with a high affinity for phosphoinositides and a unique membrane-inserting prong upon the concave surface. Combined structural, biochemical and reverse genetic approaches in zebrafish define an important role for Syndapin orthologue, Pacsin3, in the early formation of the notochord during embryonic development. In pacsin3-morphant embryos, midline convergence of notochord precursors is defective as axial mesodermal cells fail to polarize, migrate and differentiate properly. The pacsin3 morphant phenotype of a stunted body axis and contorted trunk is rescued by ectopic expression of Drosophila Syndapin, and depends critically on both the prong that protrudes from the surface of the bowed Syndapin EFC domain and the ability of the antiparallel dimer to bind tightly to phosphoinositides. Our data confirm linkage between directional migration, endocytosis and cell specification during embryonic morphogenesis and highlight a key role for Pacsin3 in this coupling in the notochord.

Structural requirements for PACSIN/Syndapin operation during zebrafish embryonic notochord development.

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Melissa A Edeling

2009-12-01

Full Text Available PACSIN/Syndapin proteins are membrane-active scaffolds that participate in endocytosis. The structure of the Drosophila Syndapin N-terminal EFC domain reveals a crescent shaped antiparallel dimer with a high affinity for phosphoinositides and a unique membrane-inserting prong upon the concave surface. Combined structural, biochemical and reverse genetic approaches in zebrafish define an important role for Syndapin orthologue, Pacsin3, in the early formation of the notochord during embryonic development. In pacsin3-morphant embryos, midline convergence of notochord precursors is defective as axial mesodermal cells fail to polarize, migrate and differentiate properly. The pacsin3 morphant phenotype of a stunted body axis and contorted trunk is rescued by ectopic expression of Drosophila Syndapin, and depends critically on both the prong that protrudes from the surface of the bowed Syndapin EFC domain and the ability of the antiparallel dimer to bind tightly to phosphoinositides. Our data confirm linkage between directional migration, endocytosis and cell specification during embryonic morphogenesis and highlight a key role for Pacsin3 in this coupling in the notochord.

Functional Brachyury binding sites establish a temporal read-out of gene expression in the Ciona notochord.

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Lavanya Katikala

2013-10-01

Full Text Available The appearance of the notochord represented a milestone in Deuterostome evolution. The notochord is necessary for the development of the chordate body plan and for the formation of the vertebral column and numerous organs. It is known that the transcription factor Brachyury is required for notochord formation in all chordates, and that it controls transcription of a large number of target genes. However, studies of the structure of the cis-regulatory modules (CRMs through which this control is exerted are complicated in vertebrates by the genomic complexity and the pan-mesodermal expression territory of Brachyury. We used the ascidian Ciona, in which the single-copy Brachyury is notochord-specific and CRMs are easily identifiable, to carry out a systematic characterization of Brachyury-downstream notochord CRMs. We found that Ciona Brachyury (Ci-Bra controls most of its targets directly, through non-palindromic binding sites that function either synergistically or individually to activate early- and middle-onset genes, respectively, while late-onset target CRMs are controlled indirectly, via transcriptional intermediaries. These results illustrate how a transcriptional regulator can efficiently shape a shallow gene regulatory network into a multi-tiered transcriptional output, and provide insights into the mechanisms that establish temporal read-outs of gene expression in a fast-developing chordate embryo.

Functional Brachyury binding sites establish a temporal read-out of gene expression in the Ciona notochord.

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Katikala, Lavanya; Aihara, Hitoshi; Passamaneck, Yale J; Gazdoiu, Stefan; José-Edwards, Diana S; Kugler, Jamie E; Oda-Ishii, Izumi; Imai, Janice H; Nibu, Yutaka; Di Gregorio, Anna

2013-10-01

The appearance of the notochord represented a milestone in Deuterostome evolution. The notochord is necessary for the development of the chordate body plan and for the formation of the vertebral column and numerous organs. It is known that the transcription factor Brachyury is required for notochord formation in all chordates, and that it controls transcription of a large number of target genes. However, studies of the structure of the cis-regulatory modules (CRMs) through which this control is exerted are complicated in vertebrates by the genomic complexity and the pan-mesodermal expression territory of Brachyury. We used the ascidian Ciona, in which the single-copy Brachyury is notochord-specific and CRMs are easily identifiable, to carry out a systematic characterization of Brachyury-downstream notochord CRMs. We found that Ciona Brachyury (Ci-Bra) controls most of its targets directly, through non-palindromic binding sites that function either synergistically or individually to activate early- and middle-onset genes, respectively, while late-onset target CRMs are controlled indirectly, via transcriptional intermediaries. These results illustrate how a transcriptional regulator can efficiently shape a shallow gene regulatory network into a multi-tiered transcriptional output, and provide insights into the mechanisms that establish temporal read-outs of gene expression in a fast-developing chordate embryo.

Transient infection of the zebrafish notochord with E. coli induces chronic inflammation

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Mai Nguyen-Chi

2014-07-01

Full Text Available Zebrafish embryos and larvae are now well-established models in which to study infectious diseases. Infections with non-pathogenic Gram-negative Escherichia coli induce a strong and reproducible inflammatory response. Here, we study the cellular response of zebrafish larvae when E. coli bacteria are injected into the notochord and describe the effects. First, we provide direct evidence that the notochord is a unique organ that is inaccessible to leukocytes (macrophages and neutrophils during the early stages of inflammation. Second, we show that notochord infection induces a host response that is characterised by rapid clearance of the bacteria, strong leukocyte recruitment around the notochord and prolonged inflammation that lasts several days after bacteria clearance. During this inflammatory response, il1b is first expressed in macrophages and subsequently at high levels in neutrophils. Moreover, knock down of il1b alters the recruitment of neutrophils to the notochord, demonstrating the important role of this cytokine in the maintenance of inflammation in the notochord. Eventually, infection of the notochord induces severe defects of the notochord that correlate with neutrophil degranulation occurring around this tissue. This is the first in vivo evidence that neutrophils can degranulate in the absence of a direct encounter with a pathogen. Persistent inflammation, neutrophil infiltration and restructuring of the extracellular matrix are defects that resemble those seen in bone infection and in some chondropathies. As the notochord is a transient embryonic structure that is closely related to cartilage and bone and that contributes to vertebral column formation, we propose infection of the notochord in zebrafish larvae as a new model to study the cellular and molecular mechanisms underlying cartilage and bone inflammation.

Did the notochord evolve from an ancient axial muscle? The axochord hypothesis.

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Brunet, Thibaut; Lauri, Antonella; Arendt, Detlev

2015-08-01

The origin of the notochord is one of the key remaining mysteries of our evolutionary ancestry. Here, we present a multi-level comparison of the chordate notochord to the axochord, a paired axial muscle spanning the ventral midline of annelid worms and other invertebrates. At the cellular level, comparative molecular profiling in the marine annelids P. dumerilii and C. teleta reveals expression of similar, specific gene sets in presumptive axochordal and notochordal cells. These cells also occupy corresponding positions in a conserved anatomical topology and undergo similar morphogenetic movements. At the organ level, a detailed comparison of bilaterian musculatures reveals that most phyla form axochord-like muscles, suggesting that such a muscle was already present in urbilaterian ancestors. Integrating comparative evidence at the cell and organ level, we propose that the notochord evolved by modification of a ventromedian muscle followed by the assembly of an axial complex supporting swimming in vertebrate ancestors. © 2015 The Authors. Bioessays published by WILEY Periodicals, Inc.

Formation, function, and exhaustion of notochordal cytoplasmic vacuoles within intervertebral disc: current understanding and speculation

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Sinkemani, Arjun; Xie, Zhi-Yang; Shi, Rui; Wei, Ji-Nan; Wu, Xiao-Tao

2017-01-01

Notochord nucleus pulposus cells are characteristic of containing abundant and giant cytoplasmic vacuoles. This review explores the embryonic formation, biological function, and postnatal exhaustion of notochord vacuoles, aiming to characterize the signal network transforming the vacuolated nucleus pulposus cells into the vacuole-less chondrocytic cells. Embryonically, the cytoplasmic vacuoles within vertebrate notochord originate from an evolutionarily conserved vacuolation process during neurulation, which may continue to provide mechanical and signal support in constructing a mammalian intervertebral disc. For full vacuolation, a vacuolating specification from dorsal organizer cells, synchronized convergent extension, well-structured notochord sheath, and sufficient post-Golgi trafficking in notochord cells are required. Postnatally, age-related and species-specific exhaustion of vacuolated nucleus pulposus cells could be potentiated by Fas- and Fas ligand-induced apoptosis, intolerance to mechanical stress and nutrient deficiency, vacuole-mediated proliferation check, and gradual de-vacuolation within the avascular and compression-loaded intervertebral disc. These results suggest that the notochord vacuoles are active and versatile organelles for both embryonic notochord and postnatal nucleus pulposus, and may provide novel information on intervertebral disc degeneration to guide cell-based regeneration. PMID:28915712

Transient infection of the zebrafish notochord with E. coli induces chronic inflammation.

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Nguyen-Chi, Mai; Phan, Quang Tien; Gonzalez, Catherine; Dubremetz, Jean-François; Levraud, Jean-Pierre; Lutfalla, Georges

2014-07-01

Zebrafish embryos and larvae are now well-established models in which to study infectious diseases. Infections with non-pathogenic Gram-negative Escherichia coli induce a strong and reproducible inflammatory response. Here, we study the cellular response of zebrafish larvae when E. coli bacteria are injected into the notochord and describe the effects. First, we provide direct evidence that the notochord is a unique organ that is inaccessible to leukocytes (macrophages and neutrophils) during the early stages of inflammation. Second, we show that notochord infection induces a host response that is characterised by rapid clearance of the bacteria, strong leukocyte recruitment around the notochord and prolonged inflammation that lasts several days after bacteria clearance. During this inflammatory response, il1b is first expressed in macrophages and subsequently at high levels in neutrophils. Moreover, knock down of il1b alters the recruitment of neutrophils to the notochord, demonstrating the important role of this cytokine in the maintenance of inflammation in the notochord. Eventually, infection of the notochord induces severe defects of the notochord that correlate with neutrophil degranulation occurring around this tissue. This is the first in vivo evidence that neutrophils can degranulate in the absence of a direct encounter with a pathogen. Persistent inflammation, neutrophil infiltration and restructuring of the extracellular matrix are defects that resemble those seen in bone infection and in some chondropathies. As the notochord is a transient embryonic structure that is closely related to cartilage and bone and that contributes to vertebral column formation, we propose infection of the notochord in zebrafish larvae as a new model to study the cellular and molecular mechanisms underlying cartilage and bone inflammation. © 2014. Published by The Company of Biologists Ltd.

The lining of the gut in the developing rat embryo. Its relation to the hypoblast (primary endoderm) and the notochord

NARCIS (Netherlands)

Lamers, W. H.; Spliet, W. G.; Langemeyer, R. A.

1987-01-01

A light microscopical study of the morphogenesis of the gut in the rat embryo was undertaken to provide a careful map of temporal changes in the topographical relations of the (definitive) endoderm, the notochord and the hypoblast (primary endoderm). The borderline between the (definitive) endoderm

Distribution of some Glycoconjugates in the Notochord and Developing Gut during Early Morphogenesis in Balb/c Mouse Embryos

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Mohammad M. Hassanzadeh-Taheri

2012-03-01

Full Text Available Background: Embryonic endoderm germinal layer, affected by notochord inductions, forms the primary gut epithelium and parenchyma of its derived organs. This study aims to determine some expressed glycoconjugates and their potential function in notochord and developing gut.Materials and Methods : In this descriptive-analytical study, 9 and 10 embryonic days (ED of Balb/c mouse embryos were fixed in formalin and microscopic sections were prepared from them. These sections were processed for histochemical studies and then they were incubated with 6 different HRP conjugated lectins, including VVA, SBA, and PNA specific to identify terminal sugar (N-acetylgalactosamine (GalNac and lectins of GSA1-B4, LTA and WGA were respectively to identify the terminal sugars of galactose, fructose and sialic acid.Results: The study results showed that the reactions of notochord and developing gut to VVA lectin were moderate on the 9ED and on the 10ED, they showed a significant difference (p < 0.001 from the day before and were severely assessed. Other GalNac specific lectins react severely and almost similarly to notochord and developing gut on the studied days. The other lectins in these two organs did not react similarly.Conclusion: According to the findings of this study, it seems that glycoconjugates with GalNac-terminal sugar probably have played a key role in differentiations of notochord and developing gut and may be involved in the interactions between these two organs.

Integrated microarray and ChIP analysis identifies multiple Foxa2 dependent target genes in the notochord.

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Tamplin, Owen J; Cox, Brian J; Rossant, Janet

2011-12-15

The node and notochord are key tissues required for patterning of the vertebrate body plan. Understanding the gene regulatory network that drives their formation and function is therefore important. Foxa2 is a key transcription factor at the top of this genetic hierarchy and finding its targets will help us to better understand node and notochord development. We performed an extensive microarray-based gene expression screen using sorted embryonic notochord cells to identify early notochord-enriched genes. We validated their specificity to the node and notochord by whole mount in situ hybridization. This provides the largest available resource of notochord-expressed genes, and therefore candidate Foxa2 target genes in the notochord. Using existing Foxa2 ChIP-seq data from adult liver, we were able to identify a set of genes expressed in the notochord that had associated regions of Foxa2-bound chromatin. Given that Foxa2 is a pioneer transcription factor, we reasoned that these sites might represent notochord-specific enhancers. Candidate Foxa2-bound regions were tested for notochord specific enhancer function in a zebrafish reporter assay and 7 novel notochord enhancers were identified. Importantly, sequence conservation or predictive models could not have readily identified these regions. Mutation of putative Foxa2 binding elements in two of these novel enhancers abrogated reporter expression and confirmed their Foxa2 dependence. The combination of highly specific gene expression profiling and genome-wide ChIP analysis is a powerful means of understanding developmental pathways, even for small cell populations such as the notochord. Copyright © 2011 Elsevier Inc. All rights reserved.

Loss of col8a1a Function during Zebrafish Embryogenesis Results in Congenital Vertebral Malformations

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Gray, Ryan S.; Wilm, Thomas; Smith, Jeff; Bagnat, Michel; Dale, Rodney M.; Topczewski, Jacek; Johnson, Stephen L.; Solnica-Krezel, Lilianna

2014-01-01

Congenital vertebral malformations (CVM) occur in 1 in 1,000 live births and in many cases can cause spinal deformities, such as scoliosis, and result in disability and distress of affected individuals. Many severe forms of the disease, such as spondylocostal dystostosis, are recessive monogenic traits affecting somitogenesis, however the etiologies of the majority of CVM cases remain undetermined. Here we demonstrate that morphological defects of the notochord in zebrafish can generate congenital-type spine defects. We characterize three recessive zebrafish leviathan/col8a1a mutant alleles (m531, vu41, vu105) that disrupt collagen type VIII alpha1a (col8a1a), and cause folding of the embryonic notochord and consequently adult vertebral column malformations. Furthermore, we provide evidence that a transient loss of col8a1a function or inhibition of Lysyl oxidases with drugs during embryogenesis was sufficient to generate vertebral fusions and scoliosis in the adult spine. Using periodic imaging of individual zebrafish, we correlate focal notochord defects of the embryo with vertebral malformations (VM) in the adult. Finally, we show that bends and kinks in the notochord can lead to aberrant apposition of osteoblasts normally confined to well-segmented areas of the developing vertebral bodies. Our results afford a novel mechanism for the formation of VM, independent of defects of somitogenesis, resulting from aberrant bone deposition at regions of misshapen notochord tissue. PMID:24333517

Zebrafish IGF genes: gene duplication, conservation and divergence, and novel roles in midline and notochord development.

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Shuming Zou

Full Text Available Insulin-like growth factors (IGFs are key regulators of development, growth, and longevity. In most vertebrate species including humans, there is one IGF-1 gene and one IGF-2 gene. Here we report the identification and functional characterization of 4 distinct IGF genes (termed as igf-1a, -1b, -2a, and -2b in zebrafish. These genes encode 4 structurally distinct and functional IGF peptides. IGF-1a and IGF-2a mRNAs were detected in multiple tissues in adult fish. IGF-1b mRNA was detected only in the gonad and IGF-2b mRNA only in the liver. Functional analysis showed that all 4 IGFs caused similar developmental defects but with different potencies. Many of these embryos had fully or partially duplicated notochords, suggesting that an excess of IGF signaling causes defects in the midline formation and an expansion of the notochord. IGF-2a, the most potent IGF, was analyzed in depth. IGF-2a expression caused defects in the midline formation and expansion of the notochord but it did not alter the anterior neural patterning. These results not only provide new insights into the functional conservation and divergence of the multiple igf genes but also reveal a novel role of IGF signaling in midline formation and notochord development in a vertebrate model.

HNK-1 immunoreactivity during early morphogenesis of the head region in a nonmodel vertebrate, crocodile embryo

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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.

Znrg, a novel gene expressed mainly in the developing notochord of zebrafish.

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Zhou, Yaping; Xu, Yan; Li, Jianzhen; Liu, Yao; Zhang, Zhe; Deng, Fengjiao

2010-06-01

The notochord, a defining characteristic of the chordate embryo is a critical midline structure required for axial skeletal formation in vertebrates, and acts as a signaling center throughout embryonic development. We utilized the digital differential display program of the National Center for Biotechnology Information, and identified a contig of expressed sequence tags (no. Dr. 83747) from the zebrafish ovary library in Genbank. Full-length cDNA of the identified gene was cloned by 5'- and 3'- RACE, and the resulting sequence was confirmed by polymerase chain reaction and sequencing. The cDNA clone contains 2,505 base pairs and encodes a novel protein of 707 amino acids that shares no significant homology with any known proteins. This gene was expressed in mature oocytes and at the one-cell stage, and persisted until the 5th day of development, as determined by RT-PCR. Transcripts were detected by whole-mount RNA in situ hybridization from the two-cell stage to 72 h of embryonic development. This gene was uniformly distributed from the cleavage stage up to the blastula stage. During early gastrulation, it was present in the dorsal region, and became restricted to the notochord and pectoral fin at 48 and 72 h of embryonic development. Based on its abundance in the notochord, we hypothesized that the novel gene may play an important role in notochord development in zebrafish; we named this gene, zebrafish notochord-related gene, or znrg.

Identification of a new mineralized tissue in the notochord of reared Siberian sturgeon (Acipenser baerii).

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Leprévost, Amandine; Azaïs, Thierry; Trichet, Michael; Sire, Jean-Yves

2017-11-01

In a study aiming to improve knowledge on the mineralization of the axial skeleton in reared Siberian sturgeon (Acipenser baerii Brandt, 1869), we discovered a new mineralized tissue within the notochord. To our knowledge, such a structure has never been reported in any vertebrate species with the exception of the pathological mineralization of the notochord remains in degenerative intervertebral disks of mammals. Here, we describe this enigmatic tissue using X-ray microtomography, histological analyses and solid state NMR-spectroscopy. We also performed a 1-year monitoring of the mineral content (MC) of the notochord in relation with seasonal variations of temperature. In all specimens studied from 2-year-old juveniles onwards, this mineralized structure was found within a particular region of the notochord called funiculus. This feature first appears in the abdominal region then extends posteriorly with ageing, while the notochord MC also increases. The mineral phase is mainly composed of amorphous calcium phosphate, a small amount of which changes into hydroxyapatite with ageing. The putative role of this structure is discussed as either a store of minerals available for the phosphocalcic metabolism, or a mechanical support in a species with a poorly mineralized axial skeleton. A pathological feature putatively related to rearing conditions is also discussed. © 2017 Wiley Periodicals, Inc.

Giant notochordal hamartoma of intraosseous origin: a newly reported benign entity to be distinguished from chordoma. Report of two cases

International Nuclear Information System (INIS)

Mirra, J.M.; Brien, E.W.

2001-01-01

Two cases are reported of a newly described intraosseous entity of vertebral bodies deemed ''giant notochordal hamartoma of intraosseous origin''. This entity is commonly mistaken for chordoma and must be distinguished from it as the consequences of misinterpretation may be serious. The clinical, radiological and histologic criteria that can be used to distinguish these two entities are emphasized. Included is a proposed pathogenesis for this lesion, its probable notochordal origin, and a review of other probable cases. (orig.)

Zebrafish scarb2a insertional mutant reveals a novel function for the Scarb2/Limp2 receptor in notochord development.

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Diaz-Tellez, Abigail; Zampedri, Cecilia; Ramos-Balderas, Jose L; García-Hernández, Fernando; Maldonado, Ernesto

2016-04-01

Scarb2 or Limp2 belong to a subfamily of Scavenger receptors described as lysosomal transmembrane glycosylated receptors, that are mutated in the human syndrome AMRF (action myoclonus-renal failure). The zebrafish insertional mutant scarb2a(hi1463Tg) has notochord defects, the notochord is a defining feature of chordates running along the center of the longitudinal axis and it is essential for forming the spinal column in all vertebrates. There are three paralogous scarb2 genes in zebrafish; scarb2a, scarb2b, and scarb2c. Both Scarb2a and Scarb2b proteins lack the classical di-leucine motif. We found that scarb2a(hi1463Tg) homozygous zebrafish embryos have a null mutation impairing vacuole formation in the notochord and simultaneously disrupting proper formation of the basement membrane resulting in its thickening at the ventral side of the notochord, which may be the cause for the anomalous upward bending observed in the trunk. Through whole-mount in situ hybridization, we detected scarb2a mRNA expression in the notochord and in the brain early in development. However, it is puzzling that scarb2a notochord mRNA expression is short-lived in the presumptive notochord and precedes the complete differentiation of the notochord. This work describes a novel function for the Scarb2 receptor as an essential glycoprotein for notochord development. © 2016 Wiley Periodicals, Inc.

Wnt signaling maintains the notochord fate for progenitor cells and supports the posterior extension of the notochord.

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Ukita, Kanako; Hirahara, Shino; Oshima, Naoko; Imuta, Yu; Yoshimoto, Aki; Jang, Chuan-Wei; Oginuma, Masayuki; Saga, Yumiko; Behringer, Richard R; Kondoh, Hisato; Sasaki, Hiroshi

2009-10-01

The notochord develops from notochord progenitor cells (NPCs) and functions as a major signaling center to regulate trunk and tail development. NPCs are initially specified in the node by Wnt and Nodal signals at the gastrula stage. However, the underlying mechanism that maintains the NPCs throughout embryogenesis to contribute to the posterior extension of the notochord remains unclear. Here, we demonstrate that Wnt signaling in the NPCs is essential for posterior extension of the notochord. Genetic labeling revealed that the Noto-expressing cells in the ventral node contribute the NPCs that reside in the tail bud. Robust Wnt signaling in the NPCs was observed during posterior notochord extension. Genetic attenuation of the Wnt signal via notochord-specific beta-catenin gene ablation resulted in posterior truncation of the notochord. In the NPCs of such mutant embryos, the expression of notochord-specific genes was down-regulated, and an endodermal marker, E-cadherin, was observed. No significant alteration of cell proliferation or apoptosis of the NPCs was detected. Taken together, our data indicate that the NPCs are derived from Noto-positive node cells, and are not fully committed to a notochordal fate. Sustained Wnt signaling is required to maintain the NPCs' notochordal fate.

Prenatal Evidence of Persistent Notochord and Absent Sacrum Caused by a Mutation in the T (Brachyury Gene

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F. Fontanella

2016-01-01

Full Text Available Caudal regression syndrome (CRS is a rare congenital disorder characterized by developmental abnormalities of caudal spinal segments. To date, the etiology of CRS is unclear; sporadic cases are strongly associated with maternal diabetes, while familiar recurrence is infrequent. We describe in detail the prenatal clinical and sonographic findings of a recently described hereditary caudal regression syndrome, in four fetuses reported to be homozygous for a mutation in the T (brachyury gene. The syndrome occurred in three consanguineous, but unrelated families, originating from the same geographical area. All affected fetuses had persistence of the notochord in association with abnormal vertebral ossification, sacral agenesis, and bilateral clubfoot. These findings suggest that, in case of prenatal diagnosis of sacral agenesis, an advanced ultrasound examination should assess the vertebral ossification and the rare persistence of the notochord, in order to rule the involvement of the T gene.

Wnt signaling maintains the notochord fate for progenitor cells and supports the posterior extension of the notochord

OpenAIRE

Ukita, Kanako; Hirahara, Shino; Oshima, Naoko; Imuta, Yu; Yoshimoto, Aki; Jang, Chuan-Wei; Oginuma, Masayuki; Saga, Yumiko; Behringer, Richard R.; Kondoh, Hisato; Sasaki, Hiroshi

2009-01-01

The notochord develops from notochord progenitor cells (NPCs) and functions as a major signaling center to regulate trunk and tail development. NPCs are initially specified in the node by Wnt and Nodal signals at the gastrula stage. However, the underlying mechanism that maintains the NPCs throughout embryogenesis to contribute to the posterior extension of the notochord remains unclear. Here, we demonstrate that Wnt signaling in the NPCs is essential for posterior extension of the notochord....

Apoptosis regulates notochord development in Xenopus

OpenAIRE

Malikova, Marina; Van Stry, Melanie; Symes, Karen

2007-01-01

The notochord is the defining characteristic of the chordate embryo, and plays critical roles as a signaling center and as the primitive skeleton. In this study we show that early notochord development in Xenopus embryos is regulated by apoptosis. We find apoptotic cells in the notochord beginning at the neural groove stage and increasing in number as the embryo develops. These dying cells are distributed in an anterior to posterior pattern that is correlated with notochord extension through ...

The notochord in Atlantic salmon (Salmo salar L.) undergoes profound morphological and mechanical changes during development.

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Kryvi, Harald; Rusten, Iselin; Fjelldal, Per Gunnar; Nordvik, Kari; Totland, Geir K; Karlsen, Tine; Wiig, Helge; Long, John H

2017-11-01

We present the development of the notochord of the Atlantic salmon (Salmo salar L.), from early embryo to sexually mature fish. Over the salmon's lifespan, profound morphological changes occur. Cells and gross structures of the notochord reorganize twice. In the embryo, the volume of the notochord is dominated by large, vacuolated chordocytes; each cell can be modeled as a hydrostat organized into a larger cellular-hydrostat network, structurally bound together with desmosomes. After the embryo hatches and grows into a fry, vacuolated chordocytes disappear, replaced by extracellular lacunae. The formation of mineralized, segmental chordacentra stiffens the notochord and creates intervertebral joints, where tissue strain during lateral bending is now focused. As development proceeds towards the parr stage, a process of devacuolization and intracellular filament accumulation occur, forming highly dense, non-vacuolated chordocytes. As extracellular lacunae enlarge, they are enclosed by dense filamentous chordocytes that form transverse intervertebral septa, which are connected to the intervertebral ligaments, and a longitudinal notochordal strand. In the vertebral column of pelagic adults, large vacuolated chordocytes reappear; cells of this secondary population have a volume up to 19 000 times larger than the primary vacuolated chordocytes of the early notochord. In adults the lacunae have diminished in relative size. Hydrostatic pressure within the notochord increases significantly during growth, from 525 Pa in the alevins to 11 500 Pa in adults, at a rate of increase with total body length greater than that expected by static stress similarity. Pressure and morphometric measurements were combined to estimate the stress in the extracellular material of the notochordal sheath and intervertebral ligaments and the flexural stiffness of the axial skeleton. The functional significance of the morphological changes in the axial skeleton is discussed in relation to the

Evolutionary changes in the notochord genetic toolkit: a comparative analysis of notochord genes in the ascidian Ciona and the larvacean Oikopleura.

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Kugler, Jamie E; Kerner, Pierre; Bouquet, Jean-Marie; Jiang, Di; Di Gregorio, Anna

2011-01-20

The notochord is a defining feature of the chordate clade, and invertebrate chordates, such as tunicates, are uniquely suited for studies of this structure. Here we used a well-characterized set of 50 notochord genes known to be targets of the notochord-specific Brachyury transcription factor in one tunicate, Ciona intestinalis (Class Ascidiacea), to begin determining whether the same genetic toolkit is employed to build the notochord in another tunicate, Oikopleura dioica (Class Larvacea). We identified Oikopleura orthologs of the Ciona notochord genes, as well as lineage-specific duplicates for which we determined the phylogenetic relationships with related genes from other chordates, and we analyzed their expression patterns in Oikopleura embryos. Of the 50 Ciona notochord genes that were used as a reference, only 26 had clearly identifiable orthologs in Oikopleura. Two of these conserved genes appeared to have undergone Oikopleura- and/or tunicate-specific duplications, and one was present in three copies in Oikopleura, thus bringing the number of genes to test to 30. We were able to clone and test 28 of these genes. Thirteen of the 28 Oikopleura orthologs of Ciona notochord genes showed clear expression in all or in part of the Oikopleura notochord, seven were diffusely expressed throughout the tail, six were expressed in tissues other than the notochord, while two probes did not provide a detectable signal at any of the stages analyzed. One of the notochord genes identified, Oikopleura netrin, was found to be unevenly expressed in notochord cells, in a pattern reminiscent of that previously observed for one of the Oikopleura Hox genes. A surprisingly high number of Ciona notochord genes do not have apparent counterparts in Oikopleura, and only a fraction of the evolutionarily conserved genes show clear notochord expression. This suggests that Ciona and Oikopleura, despite the morphological similarities of their notochords, have developed rather divergent sets

Evolutionary changes in the notochord genetic toolkit: a comparative analysis of notochord genes in the ascidian Ciona and the larvacean Oikopleura

Directory of Open Access Journals (Sweden)

Jiang Di

2011-01-01

Full Text Available Abstract Background The notochord is a defining feature of the chordate clade, and invertebrate chordates, such as tunicates, are uniquely suited for studies of this structure. Here we used a well-characterized set of 50 notochord genes known to be targets of the notochord-specific Brachyury transcription factor in one tunicate, Ciona intestinalis (Class Ascidiacea, to begin determining whether the same genetic toolkit is employed to build the notochord in another tunicate, Oikopleura dioica (Class Larvacea. We identified Oikopleura orthologs of the Ciona notochord genes, as well as lineage-specific duplicates for which we determined the phylogenetic relationships with related genes from other chordates, and we analyzed their expression patterns in Oikopleura embryos. Results Of the 50 Ciona notochord genes that were used as a reference, only 26 had clearly identifiable orthologs in Oikopleura. Two of these conserved genes appeared to have undergone Oikopleura- and/or tunicate-specific duplications, and one was present in three copies in Oikopleura, thus bringing the number of genes to test to 30. We were able to clone and test 28 of these genes. Thirteen of the 28 Oikopleura orthologs of Ciona notochord genes showed clear expression in all or in part of the Oikopleura notochord, seven were diffusely expressed throughout the tail, six were expressed in tissues other than the notochord, while two probes did not provide a detectable signal at any of the stages analyzed. One of the notochord genes identified, Oikopleura netrin, was found to be unevenly expressed in notochord cells, in a pattern reminiscent of that previously observed for one of the Oikopleura Hox genes. Conclusions A surprisingly high number of Ciona notochord genes do not have apparent counterparts in Oikopleura, and only a fraction of the evolutionarily conserved genes show clear notochord expression. This suggests that Ciona and Oikopleura, despite the morphological similarities

The origin of the vertebrate skeleton

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Pivar, Stuart

2011-01-01

The anatomy of the human and other vertebrates has been well described since the days of Leonardo da Vinci and Vesalius. The causative origin of the configuration of the bones and of their shapes and forms has been addressed over the ensuing centuries by such outstanding investigators as Goethe, Von Baer, Gegenbauer, Wilhelm His and D'Arcy Thompson, who sought to apply mechanical principles to morphogenesis. However, no coherent causative model of morphogenesis has ever been presented. This paper presents a causative model for the origin of the vertebrate skeleton, based on the premise that the body is a mosaic enlargement of self-organized patterns engrained in the membrane of the egg cell. Drawings illustrate the proposed hypothetical origin of membrane patterning and the changes in the hydrostatic equilibrium of the cytoplasm that cause topographical deformations resulting in the vertebrate body form.

An adhesome comprising laminin, dystroglycan and myosin IIA is required during notochord development in Xenopus laevis.

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Buisson, Nicolas; Sirour, Cathy; Moreau, Nicole; Denker, Elsa; Le Bouffant, Ronan; Goullancourt, Aline; Darribère, Thierry; Bello, Valérie

2014-12-01

Dystroglycan (Dg) is a transmembrane receptor for laminin that must be expressed at the right time and place in order to be involved in notochord morphogenesis. The function of Dg was examined in Xenopus laevis embryos by knockdown of Dg and overexpression and replacement of the endogenous Dg with a mutated form of the protein. This analysis revealed that Dg is required for correct laminin assembly, for cell polarization during mediolateral intercalation and for proper differentiation of vacuoles. Using mutations in the cytoplasmic domain, we identified two sites that are involved in cell polarization and are required for mediolateral cell intercalation, and a site that is required for vacuolation. Furthermore, using a proteomic analysis, the cytoskeletal non-muscle myosin IIA has been identified for the first time as a molecular link between the Dg-cytoplasmic domain and cortical actin. The data allowed us to identify the adhesome laminin-Dg-myosin IIA as being required to maintain the cortical actin cytoskeleton network during vacuolation, which is crucial to maintain the shape of notochordal cells. © 2014. Published by The Company of Biologists Ltd.

ngs (Notochord Granular Surface) Gene Encodes a Novel Type of Intermediate Filament Family Protein Essential for Notochord Maintenance in Zebrafish*

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Tong, Xiangjun; Xia, Zhidan; Zu, Yao; Telfer, Helena; Hu, Jing; Yu, Jingyi; Liu, Huan; Zhang, Quan; Sodmergen; Lin, Shuo; Zhang, Bo

2013-01-01

The notochord is an important organ involved in embryonic patterning and locomotion. In zebrafish, the mature notochord consists of a single stack of fully differentiated, large vacuolated cells called chordocytes, surrounded by a single layer of less differentiated notochordal epithelial cells called chordoblasts. Through genetic analysis of zebrafish lines carrying pseudo-typed retroviral insertions, a mutant exhibiting a defective notochord with a granular appearance was isolated, and the corresponding gene was identified as ngs (notochord granular surface), which was specifically expressed in the notochord. In the mutants, the notochord started to degenerate from 32 hours post-fertilization, and the chordocytes were then gradually replaced by smaller cells derived from chordoblasts. The granular notochord phenotype was alleviated by anesthetizing the mutant embryos with tricaine to prevent muscle contraction and locomotion. Phylogenetic analysis showed that ngs encodes a new type of intermediate filament (IF) family protein, which we named chordostatin based on its function. Under the transmission electron microcopy, bundles of 10-nm-thick IF-like filaments were enriched in the chordocytes of wild-type zebrafish embryos, whereas the chordocytes in ngs mutants lacked IF-like structures. Furthermore, chordostatin-enhanced GFP (EGFP) fusion protein assembled into a filamentous network specifically in chordocytes. Taken together, our work demonstrates that ngs encodes a novel type of IF protein and functions to maintain notochord integrity for larval development and locomotion. Our work sheds light on the mechanisms of notochord structural maintenance, as well as the evolution and biological function of IF family proteins. PMID:23132861

ngs (notochord granular surface) gene encodes a novel type of intermediate filament family protein essential for notochord maintenance in zebrafish.

Science.gov (United States)

Tong, Xiangjun; Xia, Zhidan; Zu, Yao; Telfer, Helena; Hu, Jing; Yu, Jingyi; Liu, Huan; Zhang, Quan; Sodmergen; Lin, Shuo; Zhang, Bo

2013-01-25

The notochord is an important organ involved in embryonic patterning and locomotion. In zebrafish, the mature notochord consists of a single stack of fully differentiated, large vacuolated cells called chordocytes, surrounded by a single layer of less differentiated notochordal epithelial cells called chordoblasts. Through genetic analysis of zebrafish lines carrying pseudo-typed retroviral insertions, a mutant exhibiting a defective notochord with a granular appearance was isolated, and the corresponding gene was identified as ngs (notochord granular surface), which was specifically expressed in the notochord. In the mutants, the notochord started to degenerate from 32 hours post-fertilization, and the chordocytes were then gradually replaced by smaller cells derived from chordoblasts. The granular notochord phenotype was alleviated by anesthetizing the mutant embryos with tricaine to prevent muscle contraction and locomotion. Phylogenetic analysis showed that ngs encodes a new type of intermediate filament (IF) family protein, which we named chordostatin based on its function. Under the transmission electron microcopy, bundles of 10-nm-thick IF-like filaments were enriched in the chordocytes of wild-type zebrafish embryos, whereas the chordocytes in ngs mutants lacked IF-like structures. Furthermore, chordostatin-enhanced GFP (EGFP) fusion protein assembled into a filamentous network specifically in chordocytes. Taken together, our work demonstrates that ngs encodes a novel type of IF protein and functions to maintain notochord integrity for larval development and locomotion. Our work sheds light on the mechanisms of notochord structural maintenance, as well as the evolution and biological function of IF family proteins.

Transcriptome sequencing of Atlantic salmon (Salmo salar L.) notochord prior to development of the vertebrae provides clues to regulation of positional fate, chordoblast lineage and mineralisation.

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Wang, Shou; Furmanek, Tomasz; Kryvi, Harald; Krossøy, Christel; Totland, Geir K; Grotmol, Sindre; Wargelius, Anna

2014-02-19

In teleosts such as Atlantic salmon (Salmo salar L.), segmentation and subsequent mineralisation of the notochord during embryonic stages are essential for normal vertebrae formation. However, the molecular mechanisms leading to segmentation and mineralisation of the notochord are poorly understood. The aim of this study was to identify genes/pathways acting in gradients over time and along the anterior-posterior axis during notochord segmentation and immediately prior to mineralisation of the vertebral bodies in Atlantic salmon. Notochord samples were collected from unsegmented, pre-segmented and segmented developmental stages. In each stage, the cellular core of the notochord was cut into three pieces along the longitudinal axis (anterior, mid, posterior). RNA was sequenced (22 million pair-end 100 bp/ library) and mapped to the salmon genome. 66569 transcripts were predicted and 55775 were annotated. In order to identify possible gradients leading to segmentation of the notochord, all 71 notochord-expressed hox genes were investigated, most of them displaying a typical anterior-posterior expression pattern along the notochord axis. The clustering of hox genes revealed a pattern that could be related to notochord segmentation. We further investigated how mineralisation is initiated in the notochord, and several factors related to chondrogenic lineage were identified (sox9, sox5, sox6, tgfb3, ihhb and col2a1), suggesting a cartilage-like character of the notochord. KEGG analysis of differentially expressed genes between stages revealed down-regulation of pathways associated with ECM, cell division, metabolism and development at onset of notochord segmentation. This implies that inhibitory signals produce segmentation of the notochord. One such potential inhibitory signal was identified, col11a2, which was detected in segments of non-mineralising notochord. An incomplete salmon genome was successfully used to analyse RNA-seq data from the cellular core of the

Growth type of vertebral centra and the hard tissue observed by microradiography of the rainbow trout

International Nuclear Information System (INIS)

Kubo, Y.; Asano, H.

1987-01-01

To clarify the growth feature and the structure of hard tissue, we studied the vertebral centrum of rainbow trout Salmo gairdneri, using three specimens (BL: 21.0, 29.0 and 40.0cm). We examined the ratio of centrum length to centrum diameter in each vertebral centrum and obtained the value of 0.8-1.0 in most centra. This indicates that the vertebral centra of rainbow trout belong to the so-called equivalent type. The hard tissue was observed by microradiography, with the longitudinal and cross sections (about 100 μm)cut through the center of notochordal pore. The microradiograph of thin section of centrurn differentiated serially and changed in pattern, but it is clear to sustain the specific characteristics. In longitudinal sections, the V-shaped part of bone was composed of structure like compact bone through the length of vertebral column. In cross sections, the notochordal pore was enclosed by the radial trabecular bones, the arrangement gradually turning toward the posterior centra like paired fans set opposite each other laterally

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

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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

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

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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

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

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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.

The vacuole within: How cellular organization dictates notochord function

OpenAIRE

Ellis, Kathryn; Hoffman, Brenton D.; Bagnat, Michel

2013-01-01

The notochord is an evolutionarily conserved structure that has long been known to play an important role in patterning during embryogenesis. Structurally, the notochord is composed of two cell layers: an outer epithelial-like sheath, and an inner core of cells that contain large fluid-filled vacuoles. We have recently shown these notochord vacuoles are lysosome-related organelles that form through Rab32a and vacuolar-type proton-ATPase-dependent acidification. Disruption of notochord vacuole...

A novel zinc finger protein 219-like (ZNF219L) is involved in the regulation of collagen type 2 alpha 1a (col2a1a) gene expression in zebrafish notochord.

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Lien, Huang-Wei; Yang, Chung-Hsiang; Cheng, Chia-Hsiung; Hung, Chin-Chun; Liao, Wei-Hao; Hwang, Pung-Pung; Han, Yu-San; Huang, Chang-Jen

2013-01-01

The notochord is required for body plan patterning in vertebrates, and defects in notochord development during embryogenesis can lead to diseases affecting the adult. It is therefore important to elucidate the gene regulatory mechanism underlying notochord formation. In this study, we cloned the zebrafish zinc finger 219-like (ZNF219L) based on mammalian ZNF219, which contains nine C2H2-type zinc finger domains. Through whole-mount in situ hybridization, we found that znf219L mRNA is mainly expressed in the zebrafish midbrain-hindbrain boundary, hindbrain, and notochord during development. The znf219L morpholino knockdown caused partial abnormal notochord phenotype and reduced expression of endogenous col2a1a in the notochord specifically. In addition, ZNF219L could recognize binding sites with GGGGG motifs and trigger augmented activity of the col2a1a promoter in a luciferase assay. Furthermore, in vitro binding experiments revealed that ZNF219L recognizes the GGGGG motifs in the promoter region of the zebrafish col2a1a gene through its sixth and ninth zinc finger domains. Taken together, our results reveal that ZNF219L is involved in regulating the expression of col2a1a in zebrafish notochord specifically.

Cilia-like structures anchor the amphioxus notochord to its sheath.

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Bočina, Ivana; Ljubešić, Nikola; Saraga-Babić, Mirna

2011-01-01

Body stiffness is important during undulatory locomotion in fish. In amphioxus, the myosepta play an important role in transmission of muscular forces to the notochord. In order to define the specific supporting role of the notochord in amphioxus during locomotion, the ultrastructure of 10 adult amphioxus specimens was analyzed using transmission electron microscopy. Numerous cilia-like structures were found on the surface of each notochordal cell at the sites of their attachment to the notochordal sheath. Ultrastructurally, these structures consisted of the characteristic arrangement of peripheral and central microtubular doublets and were anchored to the inner layer of the notochordal sheath. Immunohistochemically, a positive reaction to applied dynein and β-tubulin antibodies characterized the area of the cilia-like structures. We propose that reduced back-and-forth movements of the cilia-like structures might contribute to the flow of the fluid content inside the notochord, thus modulating the stiffness of the amphioxus body during its undulatory locomotion. Copyright © 2009 Elsevier GmbH. All rights reserved.

Tube formation by complex cellular processes in Ciona intestinalis notochord.

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Dong, Bo; Horie, Takeo; Denker, Elsa; Kusakabe, Takehiro; Tsuda, Motoyuki; Smith, William C; Jiang, Di

2009-06-15

In the course of embryogenesis multicellular structures and organs are assembled from constituent cells. One structural component common to many organs is the tube, which consists most simply of a luminal space surrounded by a single layer of epithelial cells. The notochord of ascidian Ciona forms a tube consisting of only 40 cells, and serves as a hydrostatic "skeleton" essential for swimming. While the early processes of convergent extension in ascidian notochord development have been extensively studied, the later phases of development, which include lumen formation, have not been well characterized. Here we used molecular markers and confocal imaging to describe tubulogenesis in the developing Ciona notochord. We found that during tubulogenesis each notochord cell established de novo apical domains, and underwent a mesenchymal-epithelial transition to become an unusual epithelial cell with two opposing apical domains. Concomitantly, extracellular luminal matrix was produced and deposited between notochord cells. Subsequently, each notochord cell simultaneously executed two types of crawling movements bi-directionally along the anterior/posterior axis on the inner surface of notochordal sheath. Lamellipodia-like protrusions resulted in cell lengthening along the anterior/posterior axis, while the retraction of trailing edges of the same cell led to the merging of the two apical domains. As a result, the notochord cells acquired endothelial-like shape and formed the wall of the central lumen. Inhibition of actin polymerization prevented the cell movement and tube formation. Ciona notochord tube formation utilized an assortment of common and fundamental cellular processes including cell shape change, apical membrane biogenesis, cell/cell adhesion remodeling, dynamic cell crawling, and lumen matrix secretion.

Ontogeny of the vertebral column of Eleutherodactylus johnstonei (Anura: Eleutherodactylidae) reveals heterochronies relative to metamorphic frogs.

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Meza-Joya, Fabio Leonardo; Ramos-Pallares, Eliana Patricia; Ramírez-Pinilla, Martha Patricia

2013-07-01

Over the last century, the morphogenesis of the vertebral column has been considered as a highly conserved process among anurans. This statement is based on the study of few metamorphic taxa, ignoring the role of developmental mechanisms underlying the evolution of specialized life-histories. Direct development in anurans has been regarded as evolutionarily derived and involves developmental recapitulation and repatterning at different levels in all amphibian taxa studied so far. Herein, we analyze the vertebral column morphogenesis of the direct-developing frog Eleutherodactylus johnstonei, describing the sequence of chondrification and ossification, based on cleared and double-stained specimens from early stage embryos to adults. In general, our results show that the morphogenesis of the vertebral column in E. johnstonei recapitulates the ancestral tadpole-like pattern of development. However, the analysis of the sequence of events using heterochrony plots shows important heterocronies relative to metamorphic species, such as a delay in the chondrification of the vertebral centra and in osteogenesis. These ontogenetic peculiarities may represent derived traits in direct-developing frogs and are possibly correlated with its unusual life history. In addition, several features of the vertebral column of E. johnstonei are highly variable from its typical morphology. We report some malformations and small deviations, which do not seem to affect the survival of individuals. These anomalies have also been found in other frogs, and include many vertebral defects, such as vertebral fusion, and vertebral preclusion and/or induction. Copyright © 2013 Wiley Periodicals, Inc.

Distinct cytoskeleton populations and extensive crosstalk control Ciona notochord tubulogenesis.

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Dong, Bo; Deng, Wei; Jiang, Di

2011-04-01

Cell elongation is a fundamental process that allows cells and tissues to adopt new shapes and functions. During notochord tubulogenesis in the ascidian Ciona intestinalis, a dramatic elongation of individual cells takes place that lengthens the notochord and, consequently, the entire embryo. We find a novel dynamic actin- and non-muscle myosin II-containing constriction midway along the anteroposterior aspect of each notochord cell during this process. Both actin polymerization and myosin II activity are required for the constriction and cell elongation. Discontinuous localization of myosin II in the constriction indicates that the actomyosin network produces local contractions along the circumference. This reveals basal constriction by the actomyosin network as a novel mechanism for cell elongation. Following elongation, the notochord cells undergo a mesenchymal-epithelial transition and form two apical domains at opposite ends. Extracellular lumens then form at the apical surfaces. We show that cortical actin and Ciona ezrin/radixin/moesin (ERM) are essential for lumen formation and that a polarized network of microtubules, which contributes to lumen development, forms in an actin-dependent manner at the apical cortex. Later in notochord tubulogenesis, when notochord cells initiate a bi-directional crawling movement on the notochordal sheath, the microtubule network rotates 90° and becomes organized as parallel bundles extending towards the leading edges of tractive lamellipodia. This process is required for the correct organization of actin-based protrusions and subsequent lumen coalescence. In summary, we establish the contribution of the actomyosin and microtubule networks to notochord tubulogenesis and reveal extensive crosstalk and regulation between these two cytoskeleton components.

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.

Collagen type XI alpha1 may be involved in the structural plasticity of the vertebral column in Atlantic salmon (Salmo salar L.).

Science.gov (United States)

Wargelius, A; Fjelldal, P G; Nordgarden, U; Grini, A; Krossøy, C; Grotmol, S; Totland, G K; Hansen, T

2010-04-01

Atlantic salmon (Salmo salar L.) vertebral bone displays plasticity in structure, osteoid secretion and mineralization in response to photoperiod. Other properties of the vertebral bone, such as mineral content and mechanical strength, are also associated with common malformations in farmed Atlantic salmon. The biological mechanisms that underlie these changes in bone physiology are unknown, and in order to elucidate which factors might be involved in this process, microarray assays were performed on vertebral bone of Atlantic salmon reared under natural or continuous light. Eight genes were upregulated in response to continuous light treatment, whereas only one of them was upregulated in a duplicate experiment. The transcriptionally regulated gene was predicted to code for collagen type XI alpha1, a protein known to be involved in controlling the diameter of fibrillar collagens in mammals. Furthermore, the gene was highly expressed in the vertebrae, where spatial expression was found in trabecular and compact bone osteoblasts and in the chordoblasts of the notochordal sheath. When we measured the expression level of the gene in the tissue compartments of the vertebrae, the collagen turned out to be 150 and 25 times more highly expressed in the notochord and compact bone respectively, relative to the expression in the trabecular bone. Gene expression was induced in response to continuous light, and reduced in compressed vertebrae. The downregulation in compressed vertebrae was due to reduced expression in the compact bone, while expression in the trabecular bone and the notochord was unaffected. These data support the hypothesis that this gene codes for a presumptive collagen type XI alpha1, which may be involved in the regulatory pathway leading to structural adaptation of the vertebral architecture.

Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord.

Directory of Open Access Journals (Sweden)

Diana S José-Edwards

2015-12-01

Full Text Available A main challenge of modern biology is to understand how specific constellations of genes are activated to differentiate cells and give rise to distinct tissues. This study focuses on elucidating how gene expression is initiated in the notochord, an axial structure that provides support and patterning signals to embryos of humans and all other chordates. Although numerous notochord genes have been identified, the regulatory DNAs that orchestrate development and propel evolution of this structure by eliciting notochord gene expression remain mostly uncharted, and the information on their configuration and recurrence is still quite fragmentary. Here we used the simple chordate Ciona for a systematic analysis of notochord cis-regulatory modules (CRMs, and investigated their composition, architectural constraints, predictive ability and evolutionary conservation. We found that most Ciona notochord CRMs relied upon variable combinations of binding sites for the transcription factors Brachyury and/or Foxa2, which can act either synergistically or independently from one another. Notably, one of these CRMs contains a Brachyury binding site juxtaposed to an (AC microsatellite, an unusual arrangement also found in Brachyury-bound regulatory regions in mouse. In contrast, different subsets of CRMs relied upon binding sites for transcription factors of widely diverse families. Surprisingly, we found that neither intra-genomic nor interspecific conservation of binding sites were reliably predictive hallmarks of notochord CRMs. We propose that rather than obeying a rigid sequence-based cis-regulatory code, most notochord CRMs are rather unique. Yet, this study uncovered essential elements recurrently used by divergent chordates as basic building blocks for notochord CRMs.

Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord.

Science.gov (United States)

José-Edwards, Diana S; Oda-Ishii, Izumi; Kugler, Jamie E; Passamaneck, Yale J; Katikala, Lavanya; Nibu, Yutaka; Di Gregorio, Anna

2015-12-01

A main challenge of modern biology is to understand how specific constellations of genes are activated to differentiate cells and give rise to distinct tissues. This study focuses on elucidating how gene expression is initiated in the notochord, an axial structure that provides support and patterning signals to embryos of humans and all other chordates. Although numerous notochord genes have been identified, the regulatory DNAs that orchestrate development and propel evolution of this structure by eliciting notochord gene expression remain mostly uncharted, and the information on their configuration and recurrence is still quite fragmentary. Here we used the simple chordate Ciona for a systematic analysis of notochord cis-regulatory modules (CRMs), and investigated their composition, architectural constraints, predictive ability and evolutionary conservation. We found that most Ciona notochord CRMs relied upon variable combinations of binding sites for the transcription factors Brachyury and/or Foxa2, which can act either synergistically or independently from one another. Notably, one of these CRMs contains a Brachyury binding site juxtaposed to an (AC) microsatellite, an unusual arrangement also found in Brachyury-bound regulatory regions in mouse. In contrast, different subsets of CRMs relied upon binding sites for transcription factors of widely diverse families. Surprisingly, we found that neither intra-genomic nor interspecific conservation of binding sites were reliably predictive hallmarks of notochord CRMs. We propose that rather than obeying a rigid sequence-based cis-regulatory code, most notochord CRMs are rather unique. Yet, this study uncovered essential elements recurrently used by divergent chordates as basic building blocks for notochord CRMs.

First histologically confirmed case of a classic chordoma arising in a precursor benign notochordal lesion: differential diagnosis of benign and malignant notochordal lesions

International Nuclear Information System (INIS)

Yamaguchi, Takehiko; Yamato, Minoru; Saotome, Koichi

2002-01-01

The first histologically confirmed case of a classic chordoma arising in a precursor benign notochordal lesion is presented and the differential diagnosis between benign and malignant notochordal lesions is discussed. A 57-year-old man presented with a classic chordoma in the coccyx. The resected specimen demonstrated a small intraosseous benign notochordal lesion in the coccyx, which was adjacent to the classic chordoma. Also seen were two separate, similar benign lesions in the sacrum. The classic chordoma consisted of multiple lobules that were separated by thin fibrous septa and that showed cords or strands of atypical physaliphorous cells set within an abundant myxoid matrix. In contrast, the benign lesions consisted of intraosseous sheets of bland physaliphorous cells without any extracellular matrix. The affected bone trabeculae showed sclerotic reactions. It was concluded that benign and malignant notochordal lesions can be distinguished microscopically. (orig.)

Whole-organ cell shape analysis reveals the developmental basis of ascidian notochord taper.

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Veeman, Michael T; Smith, William C

2013-01-15

Here we use in toto imaging together with computational segmentation and analysis methods to quantify the shape of every cell at multiple stages in the development of a simple organ: the notochord of the ascidian Ciona savignyi. We find that cell shape in the intercalated notochord depends strongly on anterior-posterior (AP) position, with cells in the middle of the notochord consistently wider than cells at the anterior or posterior. This morphological feature of having a tapered notochord is present in many chordates. We find that ascidian notochord taper involves three main mechanisms: Planar Cell Polarity (PCP) pathway-independent sibling cell volume asymmetries that precede notochord cell intercalation; the developmental timing of intercalation, which proceeds from the anterior and posterior towards the middle; and the differential rates of notochord cell narrowing after intercalation. A quantitative model shows how the morphology of an entire developing organ can be controlled by this small set of cellular mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.

Dynamics of cell polarity in tissue morphogenesis: a comparative view from Drosophila and Ciona [version 1; referees: 2 approved

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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.

Spatiotemporal analysis of putative notochordal cell markers reveals CD24 and keratins 8, 18, and 19 as notochord-specific markers during early human intervertebral disc development.

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Rodrigues-Pinto, Ricardo; Berry, Andrew; Piper-Hanley, Karen; Hanley, Neil; Richardson, Stephen M; Hoyland, Judith A

2016-08-01

In humans, the nucleus pulposus (NP) is composed of large vacuolated notochordal cells in the fetus but, soon after birth, becomes populated by smaller, chondrocyte-like cells. Although animal studies indicate that notochord-derived cells persist in the adult NP, the ontogeny of the adult human NP cell population is still unclear. As such, identification of unique notochordal markers is required. This study was conducted to determine the spatiotemporal expression of putative human notochordal markers to aid in the elucidation of the ontogeny of adult human NP cells. Human embryos and fetuses (3.5-18 weeks post-conception (WPC)) were microdissected to isolate the spine anlagens (notochord and somites/sclerotome). Morphology of the developing IVD was assessed using hematoxylin and eosin. Expression of keratin (KRT) 8, KRT18, KRT19, CD24, GAL3, CD55, BASP1, CTGF, T, CD90, Tie2, and E-cadherin was assessed using immunohistochemistry. KRT8, KRT18, KRT19 were uniquely expressed by notochordal cells at all spine levels at all stages studied; CD24 was expressed at all stages except 3.5 WPC. While GAL3, CD55, BASP1, CTGF, and T were expressed by notochordal cells at specific stages, they were also co-expressed by sclerotomal cells. CD90, Tie2, and E-cadherin expression was not detectable in developing human spine cells at any stage. This study has identified, for the first time, the consistent expression of KRT8, KRT18, KRT19, and CD24 as human notochord-specific markers during early IVD development. Thus, we propose that these markers can be used to help ascertain the ontogeny of adult human NP cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 34:1327-1340, 2016. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc.

How was the notochord born?

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Satoh, Nori; Tagawa, Kuni; Takahashi, Hiroki

2012-01-01

More than 550 million years ago, chordates originated from a common ancestor shared with nonchordate deuterostomes by developing a novel type of larva, the "tadpole larva." The notochord is the supporting organ of the larval tail and the most prominent feature of chordates; indeed, phylum Chordata is named after this organ. In this review, we discuss the molecular mechanisms involved in the formation of the notochord over the course of chordate evolution with a special emphasis on a member of T-box gene family, Brachyury. Comparison of the decoded genome of a unicellular choanoflagellate with the genomes of sponge and cnidarians suggests that T-box gene family arose at the time of the evolution of multicellular animals. Gastrulation is a morphogenetic movement that is essential for the formation of two- or three-germ-layered embryos. Brachyury is transiently expressed in the blastopore (bp) region, where it confers on cells the ability to undergo invagination. This process is involved in the formation of the archenteron in all metazoans. This is a "primary" function of Brachyury. During the evolution of chordates, Brachyury gained an additional expression domain at the dorsal midline region of the bp. In this new expression domain, Brachyury served its "secondary" function, recruiting another set of target genes to form a dorsal axial organ, notochord. The Wnt/β-catenin, BMP/Nodal, and FGF-signaling pathways are involved in the transcriptional activation of Brachyury. We discuss the molecular mechanisms of Brachyury secondary function in the context of the dorsal-ventral (D-V) inversion theory and the aboral-dorsalization hypothesis. Although the scope of this review requires some degree of oversimplification of Brachyury function, it is beneficial to facilitate studies on the notochord formation, a central evolutionary developmental biology problem in the history of metazoan evolution, pointed out first by Alexander Kowalevsky. © 2012 Wiley Periodicals, Inc.

Insights from amphioxus into the evolution of vertebrate cartilage.

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Daniel Meulemans

2007-08-01

Full Text Available Central to the story of vertebrate evolution is the origin of the vertebrate head, a problem difficult to approach using paleontology and comparative morphology due to a lack of unambiguous intermediate forms. Embryologically, much of the vertebrate head is derived from two ectodermal tissues, the neural crest and cranial placodes. Recent work in protochordates suggests the first chordates possessed migratory neural tube cells with some features of neural crest cells. However, it is unclear how and when these cells acquired the ability to form cellular cartilage, a cell type unique to vertebrates. It has been variously proposed that the neural crest acquired chondrogenic ability by recruiting proto-chondrogenic gene programs deployed in the neural tube, pharynx, and notochord. To test these hypotheses we examined the expression of 11 amphioxus orthologs of genes involved in neural crest chondrogenesis. Consistent with cellular cartilage as a vertebrate novelty, we find that no single amphioxus tissue co-expresses all or most of these genes. However, most are variously co-expressed in mesodermal derivatives. Our results suggest that neural crest-derived cartilage evolved by serial cooption of genes which functioned primitively in mesoderm.

Tracing notochord-derived cells using a Noto-cre mouse: implications for intervertebral disc development.

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McCann, Matthew R; Tamplin, Owen J; Rossant, Janet; Séguin, Cheryle A

2012-01-01

Back pain related to intervertebral disc degeneration is the most common musculoskeletal problem, with a lifetime prevalence of 82%. The lack of effective treatment for this widespread problem is directly related to our limited understanding of disc development, maintenance and degeneration. The aim of this study was to determine the developmental origins of nucleus pulposus cells within the intervertebral disc using a novel notochord-specific Cre mouse. To trace the fate of notochordal cells within the intervertebral disc, we derived a notochord-specific Cre mouse line by targeting the homeobox gene Noto. Expression of this gene is restricted to the node and the posterior notochord during gastrulation [embryonic day 7.5 (E7.5)-E12.5]. The Noto-cre mice were crossed with a conditional lacZ reporter for visualization of notochord fate in whole-mount embryos. We performed lineage-tracing experiments to examine the contribution of the notochord to spinal development from E12.5 through to skeletally mature mice (9 months). Fate mapping studies demonstrated that, following elongation and formation of the primitive axial skeleton, the notochord gives rise to the nucleus pulposus in fully formed intervertebral discs. Cellular localization of β-galactosidase (encoded by lacZ) and cytokeratin-8 demonstrated that both notochordal cells and chondrocyte-like nucleus pulposus cells are derived from the embryonic notochord. These studies establish conclusively that notochordal cells act as embryonic precursors to all cells found within the nucleus pulposus of the mature intervertebral disc. This suggests that notochordal cells might serve as tissue-specific progenitor cells within the disc and establishes the Noto-cre mouse as a unique tool to interrogate the contribution of notochordal cells to both intervertebral disc development and disc degeneration.

Whole-organ cell shape analysis reveals the developmental basis of ascidian notochord taper

OpenAIRE

Veeman, Michael T.; Smith, William C.

2013-01-01

Here we use in toto imaging together with computational segmentation and analysis methods to quantify the shape of every cell at multiple stages in the development of a simple organ: the notochord of the ascidian Ciona savignyi. We find that cell shape in the intercalated notochord depends strongly on anterior-posterior (AP) position, with cells in the middle of the notochord consistently wider than cells at the anterior or posterior. This morphological feature of having a tapered notochord i...

Persistent Notochord in a Fetus with COL2A1 Mutation

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Elisabeth Codsi

2015-01-01

Full Text Available Multiple anomalies including micromelia, poor mineralization of the vertebrae, and a persistent notochord were identified on second trimester ultrasound in a fetus with a COL2A1 mutation. To our knowledge, this represents the first case of a persistent notochord associated with a COL2A1 mutation in humans. In this case report, we describe ultrasound and postmortem findings and review the pathogenesis associated with a persistent notochord.

Notochord manipulation does not impact oesophageal and tracheal formation from isolated foregut in 3D explant culture.

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Mc Laughlin, Danielle; Murphy, Paula; Puri, Prem

2016-01-01

Tracheo-oesophageal malformations result from disturbed foregut separation during early development. The notochord, a specialised embryonic structure, forms immediately adjacent to the dividing foregut. In the Adriamycin mouse model of oesophageal atresia, foregut and notochord abnormalities co-exist, and the site and severity of foregut malformations closely correlate to the position and extent of the notochord defects. Notochord and foregut abnormalities also co-exist in the Noggin Knockout mouse as well in a small number of human cases. The notochord is a source of powerful molecular signals during early embryogenesis, being particularly important for neural crest development. The influence of notochord signaling on the adjacent foregut is not known. The purpose of this study was to examine the impact of notochord manipulation on foregut separation using a robust 3D explant method for culturing isolated foregut which permits oeosphageal and tracheal formation in vitro. Foregut was micro-dissected from embryonic day 9 mice (License B100/4447 Irish Medicines Board), embedded in collagen and cultured for 48 h with native notochord intact (n = 6), notochord removed (n = 10) or additional notochord transplanted from stage matched controls (n = 8). Specimens were analysed for foregut morphology and molecular patterning using immunohistochemistry for Hnf3b (an endoderm marker) and Sox2 (a notochord and oesophageal marker) on cryosections. Foregut separation into distinct oesophagus and trachea was observed in isolated foregut specimens with or without their native notochord. In specimens with additional notochord transplants, foregut morphology and molecular patterning were comparable to controls whether or not the native notochord was maintained. In particular foregut separation was not disrupted by the transplantation of additional notochord at the dorsal foregut endoderm. The relationship between the embryonic foregut and notochord is complex and ill

Relative growth pattern and hard tissue of vertebral centra by microradiography of bluefin tuna

International Nuclear Information System (INIS)

Kubo, Y.; Asano, H.

1989-01-01

To clarify the growth feature and the structure of hard tissue, we studied the vertebral centrum of three species, bluefin tuna Thunnus thynnus, bigeye tuna T. obesus and skipjack Katsuwonus pelamis (BL: 44.2, 39.5 and 40.0cm respectively). We examined the ratio of cetrum length to diameter in each vertebral centrum and obtained the value of 0.9-1.3 in most centra among three species. This indicates that the examined species belong to the equivalent type of the relative growth pattern of vertebral centra. The hard tissue was observed by microradiography, with the longitudinal and cross sections (about 100 μm) cut through the center of notochordal pore. The major centra of the vertebral column were composed of characteristic simple structure like a cross, when seen in the microradiographs of cross sections. Microradiographs indicated that the bone has complicated canals with minute spaces like the bone cavities

Isolation and characterization of node/notochord-like cells from mouse embryonic stem cells

DEFF Research Database (Denmark)

Winzi, Maria K.; Hyttel, Poul; Dale, Jacqueline Kim

2011-01-01

The homeobox gene Noto is expressed in the node and its derivative the notochord. Here we use a targeted Noto-GFP reporter to isolate and characterize node/notochord-like cells derived from mouse embryonic stem cells. We find very few Noto-expressing cells after spontaneous differentiation. However......, the number of Noto-expressing cells was increased when using Activin A to induce a Foxa2- and Brachyury-expressing progenitor population, whose further differentiation into Noto-expressing cells was improved by simultaneous inhibition of BMP, Wnt, and retinoic acid signaling. Noto-GFP(+) cells expressed...... the node/notochord markers Noto, Foxa2, Shh, Noggin, Chordin, Foxj1, and Brachyury; showed a vacuolarization characteristic of notochord cells; and can integrate into midline structures when grafted into Hensen's node of gastrulating chicken embryos. The ability to generate node/notochord-like cells...

Coordinated activation of the secretory pathway during notochord formation in the Xenopus embryo.

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Tanegashima, Kosuke; Zhao, Hui; Rebbert, Martha L; Dawid, Igor B

2009-11-01

We compared the transcriptome in the developing notochord of Xenopus laevis embryos with that of other embryonic regions. A coordinated and intense activation of a large set of secretory pathway genes was observed in the notochord, but not in notochord precursors in the axial mesoderm at early gastrula stage. The genes encoding Xbp1 and Creb3l2 were also activated in the notochord. These two transcription factors are implicated in the activation of secretory pathway genes during the unfolded protein response, where cells react to the stress of a build-up of unfolded proteins in their endoplasmic reticulum. Xbp1 and Creb3l2 are differentially expressed but not differentially activated in the notochord. Reduction of expression of Xbp1 or Creb3l2 by injection of antisense morpholinos led to strong deficits in notochord but not somitic muscle development. In addition, the expression of some, but not all, genes encoding secretory proteins was inhibited by injection of xbp1 morpholinos. Furthermore, expression of activated forms of Xbp1 or Creb3l2 in animal explants could activate a similar subset of secretory pathway genes. We conclude that coordinated activation of a battery of secretory pathway genes mediated by Xbp1 and Creb/ATF factors is a characteristic and necessary feature of notochord formation.

Capture and retention of tritiated serotonin by the chick notochord

International Nuclear Information System (INIS)

Gerard, Anne; Gerard, Hubert; Dollander, Alexis

1978-01-01

The 3 day old chick notochord capacity to fix tritiated serotonin is maximal in its axis and in cephalic region. Observations permitting to find, the intracellular serotonin binding sites, contribute to an explanation of the capture mechanism and suggest a special direct role of the notochord on the monoaminergic neuron cytodifferentiation [fr

STUDY OF VERTEBRAL MORPHOGENESIS OF COBIA LARVAE, (Rachycentron canadum BY DOUBLE STAINING METHODS

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Afifah Nasukha

2012-12-01

Full Text Available Vertebral development is one of the main indicators of organism growth. The aim of this study was to know the vertebral development of cobia Rachycentron canadum in larval stage (20 day post hatch. Vertebral assay was done with double staining methods. The result showed that cobia larvae from 0 dph up to 5 dph did not have cartilage. On 5 dph up to 10 dph had pre cartilage phase composed by calcium and on 10 dph up to 18 dph were cartilage phase and marked with blue color by alcian blue. Vertebral was formed perfectly as bones on 18 dph marked with red color by alizarin red. On 20 dph, cartilage had been fully transformed to bones, and the segment of vertebral was clearly formed. Measurement showed that length of cobia vertebrae was 20.20±3.90 mm, vertebrae segment was 0.91±0.11 mm and number of vertebral segments were between 25-26 segments.

Isolation and characterization of node/notochord-like cells from mouse embryonic stem cells.

Science.gov (United States)

Winzi, Maria K; Hyttel, Poul; Dale, Jacqueline Kim; Serup, Palle

2011-11-01

The homeobox gene Noto is expressed in the node and its derivative the notochord. Here we use a targeted Noto-GFP reporter to isolate and characterize node/notochord-like cells derived from mouse embryonic stem cells. We find very few Noto-expressing cells after spontaneous differentiation. However, the number of Noto-expressing cells was increased when using Activin A to induce a Foxa2- and Brachyury-expressing progenitor population, whose further differentiation into Noto-expressing cells was improved by simultaneous inhibition of BMP, Wnt, and retinoic acid signaling. Noto-GFP(+) cells expressed the node/notochord markers Noto, Foxa2, Shh, Noggin, Chordin, Foxj1, and Brachyury; showed a vacuolarization characteristic of notochord cells; and can integrate into midline structures when grafted into Hensen's node of gastrulating chicken embryos. The ability to generate node/notochord-like cells in vitro will aid the biochemical characterization of these developmentally important structures.

Benign notochordal lesions of the axial skeleton: a review and current appraisal

International Nuclear Information System (INIS)

Kyriakos, Michael

2011-01-01

At the 1996 meeting of the International Skeletal Society, an idea was put forth that there existed symptomatic lesions of the axial skeleton, morphologically different from chordoma, that were consistent with benign notochordal remnants (rests). A review of the embryological basis for this concept is made, along with an analysis of these lesions, termed giant notochordal rests or benign notochordal cell tumors, that have been reported in the intervening 15 years, with a commentary on their relationship, if any, to chordoma. (orig.)

Evolution of vertebrate mechanosensory hair cells and inner ears: toward identifying stimuli that select mutation driven altered morphologies

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Fritzsch, Bernd; Straka, Hans

2014-01-01

Among the major distance senses of vertebrates, the ear is unique in its complex morphological changes during evolution. Conceivably, these changes enable the ear to adapt toward sensing various physically well-characterized stimuli. This review develops a scenario that integrates sensory cell with organ evolution. We propose that molecular and cellular evolution of the vertebrate hair cells occurred prior to the formation of the vertebrate ear. We previously proposed that the genes driving hair cell differentiation, were aggregated in the otic region through developmental re-patterning that generated a unique vertebrate embryonic structure, the otic placode. In agreement with the presence of graviceptive receptors in many vertebrate outgroups, it is likely that the vertebrate ear originally functioned as a simple gravity-sensing organ. Based on the rare occurrence of angular acceleration receptors in vertebrate outgroups, we further propose that the canal system evolved with a more sophisticated ear morphogenesis. This evolving morphogenesis obviously turned the initial otocyst into a complex set of canals and recesses, harboring multiple sensory epithelia each adapted to the acquisition of a specific aspect of a given physical stimulus. As support for this evolutionary progression, we provide several details of the molecular basis of ear development. PMID:24281353

From notochord formation to hereditary chordoma: the many roles of Brachyury.

Science.gov (United States)

Nibu, Yutaka; José-Edwards, Diana S; Di Gregorio, Anna

2013-01-01

Chordoma is a rare, but often malignant, bone cancer that preferentially affects the axial skeleton and the skull base. These tumors are both sporadic and hereditary and appear to occur more frequently after the fourth decade of life; however, modern technologies have increased the detection of pediatric chordomas. Chordomas originate from remnants of the notochord, the main embryonic axial structure that precedes the backbone, and share with notochord cells both histological features and the expression of characteristic genes. One such gene is Brachyury, which encodes for a sequence-specific transcription factor. Known for decades as a main regulator of notochord formation, Brachyury has recently gained interest as a biomarker and causative agent of chordoma, and therefore as a promising therapeutic target. Here, we review the main characteristics of chordoma, the molecular markers, and the clinical approaches currently available for the early detection and possible treatment of this cancer. In particular, we report on the current knowledge of the role of Brachyury and of its possible mechanisms of action in both notochord formation and chordoma etiogenesis.

Tbx2/3 is an essential mediator within the Brachyury gene network during Ciona notochord development.

Science.gov (United States)

José-Edwards, Diana S; Oda-Ishii, Izumi; Nibu, Yutaka; Di Gregorio, Anna

2013-06-01

T-box genes are potent regulators of mesoderm development in many metazoans. In chordate embryos, the T-box transcription factor Brachyury (Bra) is required for specification and differentiation of the notochord. In some chordates, including the ascidian Ciona, members of the Tbx2 subfamily of T-box genes are also expressed in this tissue; however, their regulatory relationships with Bra and their contributions to the development of the notochord remain uncharacterized. We determined that the notochord expression of Ciona Tbx2/3 (Ci-Tbx2/3) requires Ci-Bra, and identified a Ci-Tbx2/3 notochord CRM that necessitates multiple Ci-Bra binding sites for its activity. Expression of mutant forms of Ci-Tbx2/3 in the developing notochord revealed a role for this transcription factor primarily in convergent extension. Through microarray screens, we uncovered numerous Ci-Tbx2/3 targets, some of which overlap with known Ci-Bra-downstream notochord genes. Among the Ci-Tbx2/3 notochord targets are evolutionarily conserved genes, including caspases, lineage-specific genes, such as Noto4, and newly identified genes, such as MLKL. This work sheds light on a large section of the notochord regulatory circuitry controlled by T-box factors, and reveals new components of the complement of genes required for the proper formation of this structure.

Nuclei pulposi formation from the embryonic notochord occurs normally in GDF-5-deficient mice.

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Maier, Jennifer A; Harfe, Brian D

2011-11-15

The transition of the mouse embryonic notochord into nuclei pulposi was determined ("fate mapped") in vivo in growth and differentiating factor-5 (GDF-5)-null mice using the Shhcre and R26R alleles. To determine whether abnormal nuclei pulposi formation from the embryonic notochord was responsible for defects present in adult nuclei pulposi of Gdf-5-null mice. The development, maintenance, and degeneration of the intervertebral disc are not understood. Previously, we demonstrated that all cells in the adult nucleus pulposus of normal mice are derived from the embryonic notochord. Gdf-5-null mice have been reported to contain intervertebral discs in which the nucleus pulposus is abnormal. It is currently unclear if disc defects in Gdf-5-null mice arise during the formation of nuclei pulposi from the notochord during embryogenesis or result from progressive postnatal degeneration of nuclei pulposi. Gdf-5 messenger RNA expression was examined in the discs of wild-type embryos by RNA in situ hybridization to determine when and where this gene was expressed. To examine nucleus pulposus formation in Gdf-5-null mice, intervertebral discs in which embryonic notochord cells were marked were analyzed in newborn and 24-week-old mice. Our Gdf-5 messenger RNA in situ experiments determined that this gene is localized to the annulus fibrosus and not the nucleus pulposus in mouse embryos. Notochord fate-mapping experiments revealed that notochord cells in Gdf-5-null mice correctly form nuclei pulposi. Our data suggest that the defects reported in the nucleus pulposus of adult Gdf-5-null mice do not result from abnormal patterning of the embryonic notochord. The use of mouse alleles to mark cells that produce all cell types that reside in the adult nucleus pulposus will allow for a detailed examination of disc formation in other mouse mutants that have been reported to contain disc defects.

[Notochord cells enhance proliferation and phenotype-keeping of intervertebral disc chondroid cells].

Science.gov (United States)

Zhao, Xianfeng; Liu, Hao; Feng, Ganjun; Deng, Li; Li, Xiuqun; Liang, Tao

2008-08-01

To isolate and culture the chondroid cells and notochord cells from New Zealand rabbit immature nucleus pulposus (NP) in monolayer, and to evaluate the responsiveness of rabbit disc-derived chondroid cells to notochord cells with respect to cell proliferation and phenotype. The NP cells were released from the minced immature NP of 6 New Zealand rabbits (4-week-old) by 0.2% collagenase II digestion. The chondroid cells and notochord cells were purified by discontinuous gradient density centrifugation. The chondroid cells were cultured alone (group A) and co-cultured with notochord cells (group B) (1:1), and cell proliferation and phenotype including proteoglycan and collagen II were evaluated. The cells in both groups were observed by the inverted microscope, and the survival rates of the primary and passage cells were detected by toluidine blue staining. The growth curves of the second passage cells in both groups were determined by MTT. Besides, the expressions of proteoglycan and collagen II of the primary and passage cells were examined by toluidine blue and immunocytochemistry staining. The notochord cells and chondroid cells were isolated and purified. With the diameter of 10-15 microm, the notochord cell had abundant intracytoplasmic vesicles, while the chondroid cell, with the diameter of 4-6 microm, had no intracytoplasmic vesicle. The cell survival rate was 89.0%-95.3% in group A and 91.3%-96.3% in group B. There was no significant difference between the same passages in both groups (P > 0.05). The co-cultured cells (group B) increased in cell proliferation compared with the chondroid cells alone (group A) in repeated experiments. The cells in group A reached their logarithmic growth phase after 3-4 days of culture, while the cells in group B did after 2 days of culture. The cell proliferation in group B was more than that in group A after 4-day culture (P notochord cells are conducive for the proliferation and phenotype-keeping of the chondroid cells and

Effect of abnormal notochord delamination on hindgut development in the Adriamycin mouse model.

Science.gov (United States)

Sato, Hideaki; Hajduk, Piotr; Furuta, Shigeyuki; Wakisaka, Munechika; Murphy, Paula; Puri, Prem; Kitagawa, Hiroaki

2013-11-01

Adriamycin mouse model (AMM) is a model of VACTERL anomalies. Sonic hedgehog (Shh) pathway, sourced by the notochord, is implicated of anorectal malformations. We hypothesized hindgut anomalies observed in the AMM are the result of abnormal effect of the notochord. Time-mated CBA/Ca mice received two intraperitoneal injections of Adriamycin (6 mg/kg) or saline as control on embryonic day (E) 7 and 8. Fetuses were harvested from E9 to E11, stained following whole mount in situ hybridization with labeled RNA probes to detect Shh and Fork head box F1(Foxf1) transcripts. Immunolocalization with endoderm marker Hnf3β was used to visualize morphology. Embryos were scanned by OPT to obtain 3D representations of expressions. In AMM, the notochord was abnormally displaced ventrally with attachment to the hindgut endoderm in 71 % of the specimens. In 32 % of the treated embryos abnormal hindgut ended blindly in a cystic structure, and both of types were remarked in 29 % of treated embryos. Endodermal Shh and mesenchymal Foxf1 genes expression were preserved around the hindgut cystic malformation. The delamination of the developing notochord in the AMM is disrupted, which may influence signaling mechanisms from the notochord to the hindgut resulting in abnormal patterning of the hindgut.

A one-dimensional model of PCP signaling: polarized cell behavior in the notochord of the ascidian Ciona.

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Kourakis, Matthew J; Reeves, Wendy; Newman-Smith, Erin; Maury, Benoit; Abdul-Wajid, Sarah; Smith, William C

2014-11-01

Despite its importance in development and physiology the planar cell polarity (PCP) pathway remains one of the most enigmatic signaling mechanisms. The notochord of the ascidian Ciona provides a unique model for investigating the PCP pathway. Interestingly, the notochord appears to be the only embryonic structure in Ciona activating the PCP pathway. Moreover, the Ciona notochord as a single-file array of forty polarized cells is a uniquely tractable system for the study of polarization dynamics and the transmission of the PCP pathway. Here, we test models for propagation of a polarizing signal, interrogating temporal, spatial and signaling requirements. A simple cell-cell relay cascading through the entire length of the notochord is not supported; instead a more complex mechanism is revealed, with interactions influencing polarity between neighboring cells, but not distant ones. Mechanisms coordinating notochord-wide polarity remain elusive, but appear to entrain general (i.e., global) polarity even while local interactions remain important. However, this global polarizer does not appear to act as a localized, spatially-restricted determinant. Coordination of polarity along the long axis of the notochord requires the PCP pathway, a role we demonstrate is temporally distinct from this pathway's earlier role in convergent extension and intercalation. We also reveal polarity in the notochord to be dynamic: a cell's polarity state can be changed and then restored, underscoring the Ciona notochord's amenability for in vivo studies of PCP. Copyright © 2014 Elsevier Inc. All rights reserved.

Discovery, characterization and expression of a novel zebrafish gene, znfr, important for notochord formation.

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Xu, Yan; Zou, Peng; Liu, Yao; Deng, Fengjiao

2010-06-01

Genes specifically expressed in the notochord may be crucial for proper notochord development. Using the digital differential display program offered by the National Center for Biotechnology Information, we identified a novel EST sequence from a zebrafish ovary library (No. XM_701450). The full-length cDNA of this transcript was cloned by performing 3' and 5'-RACE and was further confirmed by PCR and sequencing. The resulting 614 bp gene was found to encode a novel 94 amino acid protein that did not share significant homology with any other known protein. Characterization of the genomic sequence revealed that the gene spanned 4.9 kb and was composed of four exons and three introns. RT-PCR gene expression analysis revealed that our gene of interest was expressed in ovary, kidney, brain, mature oocytes and during the early stages of embryogenesis. During embryonic development, znfr mRNA was found to be expressed in the embryonic shield, chordamesoderm and the vacuolated notochord cells by in situ hybridization. Based on this information, we hypothesize that this novel gene is an important maternal factor required for zebrafish notochord formation during early embryonic development. We have thus named this gene znfr (zebrafish notochord formation related).

Regulation of notochord-specific expression of Ci-Bra downstream genes in Ciona intestinalis embryos.

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Takahashi, Hiroki; Hotta, Kohji; Takagi, Chiyo; Ueno, Naoto; Satoh, Nori; Shoguchi, Eiichi

2010-02-01

Brachyury, a T-box transcription factor, is expressed in ascidian embryos exclusively in primordial notochord cells and plays a pivotal role in differentiation of notochord cells. Previously, we identified approximately 450 genes downstream of Ciona intestinalis Brachyury (Ci-Bra), and characterized the expression profiles of 45 of these in differentiating notochord cells. In this study, we looked for cisregulatory sequences in minimal enhancers of 20 Ci-Bra downstream genes by electroporating region within approximately 3 kb upstream of each gene fused with lacZ. Eight of the 20 reporters were expressed in notochord cells. The minimal enchancer for each of these eight genes was narrowed to a region approximately 0.5-1.0-kb long. We also explored the genome-wide and coordinate regulation of 43 Ci-Bra-downstream genes. When we determined their chromosomal localization, it became evident that they are not clustered in a given region of the genome, but rather distributed evenly over 13 of the 14 pairs of chromosomes, suggesting that gene clustering does not contribute to coordinate control of the Ci-Bra downstream gene expression. Our results might provide Insights Into the molecular mechanisms underlying notochord formation in chordates.

Muscular contractions in the zebrafish embryo are necessary to reveal thiuram-induced notochord distortions

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Teraoka, Hiroki; Urakawa, Satsuki; Nanba, Satomi; Nagai, Yuhki; Wu Dong; Imagawa, Tomohiro; Tanguay, Robert L.; Svoboda, Kurt; Handley-Goldstone, Heather M.; Stegeman, John J.; Hiraga, Takeo

2006-01-01

Dithiocarbamates form a large group of chemicals that have numerous uses in agriculture and medicine. It has been reported that dithiocarbamates, including thiuram (tetramethylthiuram disulfide), cause wavy distortions of the notochord in zebrafish and other fish embryos. In the present study, we investigated the mechanism underlying the toxicity of thiuram in zebrafish embryos. When embryos were exposed to thiuram (2-1000 nM: 0.48-240 μg/L) from 3 h post fertilization (hpf) (30% epiboly) until 24 hpf (Prim-5), all embryos develop wavy notochords, disorganized somites, and have shortened yolk sac extensions. The thiuram response was specific and did not cause growth retardation or mortality at 24 hpf. The thiuram-dependent responses showed the same concentration dependence with a waterborne EC 5 values of approximately 7 nM. Morphometric measurements revealed that thiuram does not affect the rate of notochord lengthening. However, the rate of overall body lengthening was significantly reduced in thiuram-exposed animals. Other dithiocarbamates, such as ziram, caused similar malformations to thiuram. While expression of genes involved in somitogenesis was not affected, the levels of notochord-specific transcripts were altered after the onset of malformations. Distortion of the notochord started precisely at 18 hpf, which is concomitant with onset of spontaneous rhythmic trunk contractions. Abolishment of spontaneous contractions using tricaine, α-bungarotoxin, and a paralytic mutant sofa potato, resulted in normal notochord morphology in the presence of thiuram. These results indicate that muscle activity is necessary to reveal the underlying functional deficit and suggest that the developmental target of dithiocarbamates impairs trunk plasticity through an unknown mechanism

The small molecule Mek1/2 inhibitor U0126 disrupts the chordamesoderm to notochord transition in zebrafish

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Szabó Gábor

2008-04-01

Full Text Available Abstract Background Key molecules involved in notochord differentiation and function have been identified through genetic analysis in zebrafish and mice, but MEK1 and 2 have so far not been implicated in this process due to early lethality (Mek1-/- and functional redundancy (Mek2-/- in the knockout animals. Results Here, we reveal a potential role for Mek1/2 during notochord development by using the small molecule Mek1/2 inhibitor U0126 which blocks phosphorylation of the Mek1/2 target gene Erk1/2 in vivo. Applying the inhibitor from early gastrulation until the 18-somite stage produces a specific and consistent phenotype with lack of dark pigmentation, shorter tail and an abnormal, undulated notochord. Using morphological analysis, in situ hybridization, immunhistochemistry, TUNEL staining and electron microscopy, we demonstrate that in treated embryos the chordamesoderm to notochord transition is disrupted and identify disorganization in the medial layer of the perinotochordal basement mebrane as the probable cause of the undulations and bulges in the notochord. We also examined and excluded FGF as the upstream signal during this process. Conclusion Using the small chemical U0126, we have established a novel link between MAPK-signaling and notochord differentiation. Our phenotypic analysis suggests a potential connection between the MAPK-pathway, the COPI-mediated intracellular transport and/or the copper-dependent posttranslational regulatory processes during notochord differentiation.

Cytoskeletal actin genes function downstream of HNF-3beta in ascidian notochord development.

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Jeffery, W R; Ewing, N; Machula, J; Olsen, C L; Swalla, B J

1998-11-01

We have examined the expression and regulation of cytoskeletal actin genes in ascidians with tailed (Molgula oculata) and tailless larvae (Molgula occulta). Four cDNA clones were isolated representing two pairs of orthologous cytoskeletal actin genes (CA1 and CA2), which encode proteins differing by five amino acids in the tailed and tailless species. The CA1 and CA2 genes are present in one or two copies, although several related genes may also be present in both species. Maternal CA1 and CA2 mRNA is present in small oocytes but transcript levels later decline, suggesting a role in early oogenesis. In the tailed species, embryonic CA1 and CA2 mRNAs first appear in the presumptive mesenchyme and muscle cells during gastrulation, subsequently accumulate in the presumptive notochord cells, and can be detected in these tissues through the tadpole stage. CA1 mRNAs accumulate initially in the same tissues in the tailless species but subsequently disappear, in concert with the arrest of notochord and tail development. In contrast, CA2 mRNAs were not detected in embryos of the tailless species. Fertilization of eggs of the tailless species with sperm of the tailed species, which restores the notochord and the tail, also results in the upregulation of CA1 and CA2 gene expression in hybrid embryos. Antisense oligodeoxynucleotide experiments suggest that CA1 and CA2 expression in the notochord, but not in the muscle cells, is dependent on prior expression of Mocc FHI, an ascidian HNF-3beta-like gene. The expression of the CA1 and CA2 genes in the notochord in the tailed species, downregulation in the tailless species, upregulation in interspecific hybrids, and dependence on HNF-3beta activity is consistent with a role of these genes in development of the ascidian notochord.

Notochord in Tilapia nilotica Exposed to Sublethal Dose of Malathion, S[1, 2-Di(EthoxycarbonylEthyl] Dimethyl Phosphorothiolothionate

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Edna Amparado

1992-06-01

Full Text Available Exposure of Tilapia nilotica embryos to sublethal dose of 1.0 ppm commercial grade malathion, S[1,2-di(ethoxycarbonylethyl] dimethyl phosphorothiolothionate from day-10 post fertilization resulted in notochordal aberrations. Pesticide-treated fishes exhibited constriction of the notochordal sheath, folding at the posterior sections and larger notochord than those of the control group.

Development and evolution of the vertebrate primary mouth

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Soukup, Vladimír; Horácek, Ivan; Cerny, Robert

2013-01-01

The vertebrate oral region represents a key interface between outer and inner environments, and its structural and functional design is among the limiting factors for survival of its owners. Both formation of the respective oral opening (primary mouth) and establishment of the food-processing apparatus (secondary mouth) require interplay between several embryonic tissues and complex embryonic rearrangements. Although many aspects of the secondary mouth formation, including development of the jaws, teeth or taste buds, are known in considerable detail, general knowledge about primary mouth formation is regrettably low. In this paper, primary mouth formation is reviewed from a comparative point of view in order to reveal its underestimated morphogenetic diversity among, and also within, particular vertebrate clades. In general, three main developmental modes were identified. The most common is characterized by primary mouth formation via a deeply invaginated ectodermal stomodeum and subsequent rupture of the bilaminar oral membrane. However, in salamander, lungfish and also in some frog species, the mouth develops alternatively via stomodeal collar formation contributed both by the ecto- and endoderm. In ray-finned fishes, on the other hand, the mouth forms via an ectoderm wedge and later horizontal detachment of the initially compressed oral epithelia with probably a mixed germ-layer derivation. A very intriguing situation can be seen in agnathan fishes: whereas lampreys develop their primary mouth in a manner similar to the most common gnathostome pattern, hagfishes seem to undergo a unique oropharyngeal morphogenesis when compared with other vertebrates. In discussing the early formative embryonic correlates of primary mouth formation likely to be responsible for evolutionary–developmental modifications of this area, we stress an essential role of four factors: first, positioning and amount of yolk tissue; closely related to, second, endoderm formation during

A novel zebrafish mutant with wavy-notochord: an effective biological index for monitoring the copper pollution of water from natural resources.

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Chen, Yau-Hung; Lin, Ji-Sheng

2011-02-01

We identified a novel zebrafish mutant that has wavy-notochord phenotypes, such as severely twisted notochord and posterior malformations, but has normal melanocytes. Histological evidences showed that proliferating vacuolar cells extended their growth to the muscle region, and consequently caused the wavy-notochord phenotypes. Interestingly, those malformations can be greatly reversed by exposure with copper, suggesting that copper plays an important role on wavy-notochord phenotypes. In addition, after long-term copper exposure, the surviving larvae derived from wavy-notochord mutants displayed bone malformations, such as twisted axial skeleton and osteophyte. These phenotypic changes and molecular evidences of wavy-notochord mutants are highly similar to those embryos whose lysyl oxidases activities have been inactivated. Taken together, we propose that (i) the putative mutated genes of this wavy-notochord mutant might be highly associated with the lysyl oxidase genes in zebrafish; and (ii) this fish model is an effective tool for monitoring copper pollution of water from natural resources. Copyright © 2009 Wiley Periodicals, Inc.

Animal evolution: stiff or squishy notochord origins?

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Hejnol, Andreas; Lowe, Christopher J

2014-12-01

The notochord is considered an evolutionary novelty and one of the defining characters of chordates. A new study of an annelid challenges this view and proposes an earlier evolutionary origin in the most recent common ancestor of chordates and annelids. Copyright © 2014 Elsevier Ltd. All rights reserved.

The vacuole within

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Ellis, Kathryn; Hoffman, Brenton D.; Bagnat, Michel

2013-01-01

The notochord is an evolutionarily conserved structure that has long been known to play an important role in patterning during embryogenesis. Structurally, the notochord is composed of two cell layers: an outer epithelial-like sheath, and an inner core of cells that contain large fluid-filled vacuoles. We have recently shown these notochord vacuoles are lysosome-related organelles that form through Rab32a and vacuolar-type proton-ATPase-dependent acidification. Disruption of notochord vacuoles results in a shortened embryo along the anterior-posterior axis. Interestingly, we discovered that notochord vacuoles are also essential for proper spine morphogenesis and that vacuole defects lead to scoliosis of the spine. Here we discuss the cellular organization of the notochord and how key features of its architecture allow the notochord to function in embryonic axis elongation and spine formation. PMID:23887209

Putative oncogene Brachyury (T) is essential to specify cell fate but dispensable for notochord progenitor proliferation and EMT.

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Zhu, Jianjian; Kwan, Kin Ming; Mackem, Susan

2016-04-05

The transcription factor Brachyury (T) gene is expressed throughout primary mesoderm (primitive streak and notochord) during early embryonic development and has been strongly implicated in the genesis of chordoma, a sarcoma of notochord cell origin. Additionally, T expression has been found in and proposed to play a role in promoting epithelial-mesenchymal transition (EMT) in various other types of human tumors. However, the role of T in normal mammalian notochord development and function is still not well-understood. We have generated an inducible knockdown model to efficiently and selectively deplete T from notochord in mouse embryos. In combination with genetic lineage tracing, we show that T function is essential for maintaining notochord cell fate and function. Progenitors adopt predominantly a neural fate in the absence of T, consistent with an origin from a common chordoneural progenitor. However, T function is dispensable for progenitor cell survival, proliferation, and EMT, which has implications for the therapeutic targeting of T in chordoma and other cancers.

Loss of HIF-1α in the notochord results in cell death and complete disappearance of the nucleus pulposus.

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Merceron, Christophe; Mangiavini, Laura; Robling, Alexander; Wilson, Tremika LeShan; Giaccia, Amato J; Shapiro, Irving M; Schipani, Ernestina; Risbud, Makarand V

2014-01-01

The intervertebral disc (IVD) is one of the largest avascular organs in vertebrates. The nucleus pulposus (NP), a highly hydrated and proteoglycan-enriched tissue, forms the inner portion of the IVD. The NP is surrounded by a multi-lamellar fibrocartilaginous structure, the annulus fibrosus (AF). This structure is covered superior and inferior side by cartilaginous endplates (CEP). The NP is a unique tissue within the IVD as it results from the differentiation of notochordal cells, whereas, AF and CEP derive from the sclerotome. The hypoxia inducible factor-1α (HIF-1α) is expressed in NP cells but its function in NP development and homeostasis is largely unknown. We thus conditionally deleted HIF-1α in notochordal cells and investigated how loss of this transcription factor impacts NP formation and homeostasis at E15.5, birth, 1 and 4 months of age, respectively. Histological analysis, cell lineage studies, and TUNEL assay were performed. Morphologic changes of the mutant NP cells were identified as early as E15.5, followed, postnatally, by the progressive disappearance and replacement of the NP with a novel tissue that resembles fibrocartilage. Notably, lineage studies and TUNEL assay unequivocally proved that NP cells did not transdifferentiate into chondrocyte-like cells but they rather underwent massive cell death, and were completely replaced by a cell population belonging to a lineage distinct from the notochordal one. Finally, to evaluate the functional consequences of HIF-1α deletion in the NP, biomechanical testing of mutant IVD was performed. Loss of the NP in mutant mice significantly reduced the IVD biomechanical properties by decreasing its ability to absorb mechanical stress. These findings are similar to the changes usually observed during human IVD degeneration. Our study thus demonstrates that HIF-1α is essential for NP development and homeostasis, and it raises the intriguing possibility that this transcription factor could be involved in IVD

Ciona intestinalis Noto4 contains a phosphotyrosine interaction domain and is involved in the midline intercalation of notochord cells.

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Yamada, Shigehiro; Ueno, Naoto; Satoh, Nori; Takahashi, Hiroki

2011-01-01

Brachyury plays a pivotal role in the notochord formation in ascidian embryos. Ciona intestinalis Noto4 (Ci-Noto4) was isolated as a gene downstream of Ci-Bra. This gene encodes a 307 amino-acid protein with a C-terminal phosphotyrosine interaction domain (PTB/PID). Expression of Ci-Noto4 commences at the neural plate stage and is specific to notochord cells. Suppression of Ci-Noto4 levels with specific antisense morpholino oligonucleotides resulted in the formation of two rows of notochord cells owing to a lack of midline intercalation between the bilateral populations of progenitor cells. In contrast, overexpression of Ci-Noto4 by injection of a Ci-Bra(promoter):Ci-Noto4-EGFP construct into fertilized eggs disrupted the localization of notochord cells. Ci-Noto4 overexpression did not affect cellular differentiation in the notochord, muscle, mesenchyme, or nervous system. Analysis of Ci-Noto4 regions that are responsible for its function suggested significant roles for the PTB/PID and a central region, an area with no obvious sequence similarity to other known proteins. These results suggested that PTB/PID-containing Ci-Noto4 is essential for midline intercalation of notochord cells in chordate embryos.

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

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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.

The evolutionarily conserved leprecan gene: its regulation by Brachyury and its role in the developing Ciona notochord.

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Dunn, Matthew P; Di Gregorio, Anna

2009-04-15

In Ciona intestinalis, leprecan was identified as a target of the notochord-specific transcription factor Ciona Brachyury (Ci-Bra) (Takahashi, H., Hotta, K., Erives, A., Di Gregorio, A., Zeller, R.W., Levine, M., Satoh, N., 1999. Brachyury downstream notochord differentiation in the ascidian embryo. Genes Dev. 13, 1519-1523). By screening approximately 14 kb of the Ci-leprecan locus for cis-regulatory activity, we have identified a 581-bp minimal notochord-specific cis-regulatory module (CRM) whose activity depends upon T-box binding sites located at the 3'-end of its sequence. These sites are specifically bound in vitro by a GST-Ci-Bra fusion protein, and mutations that abolish binding in vitro result in loss or decrease of regulatory activity in vivo. Serial deletions of the 581-bp notochord CRM revealed that this sequence is also able to direct expression in muscle cells through the same T-box sites that are utilized by Ci-Bra in the notochord, which are also bound in vitro by the muscle-specific T-box activators Ci-Tbx6b and Ci-Tbx6c. Additionally, we created plasmids aimed to interfere with the function of Ci-leprecan and categorized the resulting phenotypes, which consist of variable dislocations of notochord cells along the anterior-posterior axis. Together, these observations provide mechanistic insights generally applicable to T-box transcription factors and their target sequences, as well as a first set of clues on the function of Leprecan in early chordate development.

Notochord Cells in Intervertebral Disc Development and Degeneration

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McCann, Matthew R.; Séguin, Cheryle A.

2016-01-01

The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches. PMID:27252900

Notochord Cells in Intervertebral Disc Development and Degeneration

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Matthew R. McCann

2016-01-01

Full Text Available The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches.

Establishment of the Vertebrate Germ Layers.

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Tseng, Wei-Chia; Munisha, Mumingjiang; Gutierrez, Juan B; Dougan, Scott T

2017-01-01

The process of germ layer formation is a universal feature of animal development. The germ layers separate the cells that produce the internal organs and tissues from those that produce the nervous system and outer tissues. Their discovery in the early nineteenth century transformed embryology from a purely descriptive field into a rigorous scientific discipline, in which hypotheses could be tested by observation and experimentation. By systematically addressing the questions of how the germ layers are formed and how they generate overall body plan, scientists have made fundamental contributions to the fields of evolution, cell signaling, morphogenesis, and stem cell biology. At each step, this work was advanced by the development of innovative methods of observing cell behavior in vivo and in culture. Here, we take an historical approach to describe our current understanding of vertebrate germ layer formation as it relates to the long-standing questions of developmental biology. By comparing how germ layers form in distantly related vertebrate species, we find that highly conserved molecular pathways can be adapted to perform the same function in dramatically different embryonic environments.

FoxA4 favours notochord formation by inhibiting contiguous mesodermal fates and restricts anterior neural development in Xenopus embryos.

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Murgan, Sabrina; Castro Colabianchi, Aitana Manuela; Monti, Renato José; Boyadjián López, Laura Elena; Aguirre, Cecilia E; Stivala, Ernesto González; Carrasco, Andrés E; López, Silvia L

2014-01-01

In vertebrates, the embryonic dorsal midline is a crucial signalling centre that patterns the surrounding tissues during development. Members of the FoxA subfamily of transcription factors are expressed in the structures that compose this centre. Foxa2 is essential for dorsal midline development in mammals, since knock-out mouse embryos lack a definitive node, notochord and floor plate. The related gene foxA4 is only present in amphibians. Expression begins in the blastula -chordin and -noggin expressing centre (BCNE) and is later restricted to the dorsal midline derivatives of the Spemann's organiser. It was suggested that the early functions of mammalian foxa2 are carried out by foxA4 in frogs, but functional experiments were needed to test this hypothesis. Here, we show that some important dorsal midline functions of mammalian foxa2 are exerted by foxA4 in Xenopus. We provide new evidence that the latter prevents the respecification of dorsal midline precursors towards contiguous fates, inhibiting prechordal and paraxial mesoderm development in favour of the notochord. In addition, we show that foxA4 is required for the correct regionalisation and maintenance of the central nervous system. FoxA4 participates in constraining the prospective rostral forebrain territory during neural specification and is necessary for the correct segregation of the most anterior ectodermal derivatives, such as the cement gland and the pituitary anlagen. Moreover, the early expression of foxA4 in the BCNE (which contains precursors of the whole forebrain and most of the midbrain and hindbrain) is directly required to restrict anterior neural development.

Direct activation of a notochord cis-regulatory module by Brachyury and FoxA in the ascidian Ciona intestinalis.

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Passamaneck, Yale J; Katikala, Lavanya; Perrone, Lorena; Dunn, Matthew P; Oda-Ishii, Izumi; Di Gregorio, Anna

2009-11-01

The notochord is a defining feature of the chordate body plan. Experiments in ascidian, frog and mouse embryos have shown that co-expression of Brachyury and FoxA class transcription factors is required for notochord development. However, studies on the cis-regulatory sequences mediating the synergistic effects of these transcription factors are complicated by the limited knowledge of notochord genes and cis-regulatory modules (CRMs) that are directly targeted by both. We have identified an easily testable model for such investigations in a 155-bp notochord-specific CRM from the ascidian Ciona intestinalis. This CRM contains functional binding sites for both Ciona Brachyury (Ci-Bra) and FoxA (Ci-FoxA-a). By combining point mutation analysis and misexpression experiments, we demonstrate that binding of both transcription factors to this CRM is necessary and sufficient to activate transcription. To gain insights into the cis-regulatory criteria controlling its activity, we investigated the organization of the transcription factor binding sites within the 155-bp CRM. The 155-bp sequence contains two Ci-Bra binding sites with identical core sequences but opposite orientations, only one of which is required for enhancer activity. Changes in both orientation and spacing of these sites substantially affect the activity of the CRM, as clusters of identical sites found in the Ciona genome with different arrangements are unable to activate transcription in notochord cells. This work presents the first evidence of a synergistic interaction between Brachyury and FoxA in the activation of an individual notochord CRM, and highlights the importance of transcription factor binding site arrangement for its function.

Impaired intervertebral disc development and premature disc degeneration in mice with notochord-specific deletion of CCN2.

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Bedore, Jake; Sha, Wei; McCann, Matthew R; Liu, Shangxi; Leask, Andrew; Séguin, Cheryle A

2013-10-01

Currently, our ability to treat intervertebral disc (IVD) degeneration is hampered by an incomplete understanding of disc development and aging. The specific function of matricellular proteins, including CCN2, during these processes remains an enigma. The aim of this study was to determine the tissue-specific localization of CCN proteins and to characterize their role in IVD tissues during embryonic development and age-related degeneration by using a mouse model of notochord-specific CCN2 deletion. Expression of CCN proteins was assessed in IVD tissues from wild-type mice beginning on embryonic day 15.5 to 17 months of age. Given the enrichment of CCN2 in notochord-derived tissues, we generated notochord-specific CCN2-null mice to assess the impact on the IVD structure and extracellular matrix composition. Using a combination of histologic evaluation and magnetic resonance imaging (MRI), IVD health was assessed. Loss of the CCN2 gene in notochord-derived cells disrupted the formation of IVDs in embryonic and newborn mice, resulting in decreased levels of aggrecan and type II collagen and concomitantly increased levels of type I collagen within the nucleus pulposus. CCN2-knockout mice also had altered expression of CCN1 (Cyr61) and CCN3 (Nov). Mirroring its role during early development, notochord-specific CCN2 deletion accelerated age-associated degeneration of IVDs. Using a notochord-specific gene targeting strategy, this study demonstrates that CCN2 expression by nucleus pulposus cells is essential to the regulation of IVD development and age-associated tissue maintenance. The ability of CCN2 to regulate the composition of the intervertebral disc suggests that it may represent an intriguing clinical target for the treatment of disc degeneration. Copyright © 2013 by the American College of Rheumatology.

Generation of knock-in mice that express nuclear enhanced green fluorescent protein and tamoxifen-inducible Cre recombinase in the notochord from Foxa2 and T loci.

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Imuta, Yu; Kiyonari, Hiroshi; Jang, Chuan-Wei; Behringer, Richard R; Sasaki, Hiroshi

2013-03-01

The node and the notochord are important embryonic signaling centers that control embryonic pattern formation. Notochord progenitor cells present in the node and later in the posterior end of the notochord move anteriorly to generate the notochord. To understand the dynamics of cell movement during notochord development and the molecular mechanisms controlling this event, analyses of cell movements using time-lapse imaging and conditional manipulation of gene activities are required. To achieve this goal, we generated two knock-in mouse lines that simultaneously express nuclear enhanced green fluorescent protein (EGFP) and tamoxifen-inducible Cre, CreER(T2) , from two notochord gene loci, Foxa2 and T (Brachury). In Foxa2(nEGFP-CreERT2/+) and T(nEGFP-CreERT2/+) embryos, nuclei of the Foxa2 or T-expressing cells, which include the node, notochord, and endoderm (Foxa2) or wide range of posterior mesoderm (T), were labeled with EGFP at intensities that can be used for live imaging. Cre activity was also induced in cells expressing Foxa2 and T 1 day after tamoxifen administration. These mice are expected to be useful tools for analyzing the mechanisms of notochord development. Copyright © 2013 Wiley Periodicals, Inc.

The identification of transcription factors expressed in the notochord of Ciona intestinalis adds new potential players to the brachyury gene regulatory network.

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José-Edwards, Diana S; Kerner, Pierre; Kugler, Jamie E; Deng, Wei; Jiang, Di; Di Gregorio, Anna

2011-07-01

The notochord is the distinctive characteristic of chordates; however, the knowledge of the complement of transcription factors governing the development of this structure is still incomplete. Here we present the expression patterns of seven transcription factor genes detected in the notochord of the ascidian Ciona intestinalis at various stages of embryonic development. Four of these transcription factors, Fos-a, NFAT5, AFF and Klf15, have not been directly associated with the notochord in previous studies, while the others, including Spalt-like-a, Lmx-like, and STAT5/6-b, display evolutionarily conserved expression in this structure as well as in other domains. We examined the hierarchical relationships between these genes and the transcription factor Brachyury, which is necessary for notochord development in all chordates. We found that Ciona Brachyury regulates the expression of most, although not all, of these genes. These results shed light on the genetic regulatory program underlying notochord formation in Ciona and possibly other chordates. Copyright © 2011 Wiley-Liss, Inc.

The effect of novel nitrogen-rich plasma polymer coatings on the phenotypic profile of notochordal cells

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Wertheimer Michael R

2007-09-01

Full Text Available Abstract Background The loss of the notochordal cells from the nucleus pulposus is associated with ageing and disc degeneration. However, understanding the mechanisms responsible for the loss of these cells has been hampered in part due to the difficulty of culturing and maintaining their phenotype. Furthermore, little is known about the influence of the substratum on the molecular markers of notochordal cells. Methods Notochordal cells were isolated from lumbar spine of non-chondrodystrophoid dogs and cultured on N-rich plasma polymer layers, so-called "PPE:N" (N-doped plasma-polymerised ethylene, containing up to 36% [N] surfaces, for 3, 7 or 14 days. Gene expression of vimentin (VIM, pleiotrophin (PTN, matrix Gla protein (MGP, cartilage oligomeric matrix protein (COMP, keratin 18 (KRT 18, aggrecan (AGG, collagen type 1 (COL1A2, collagen type 2 (COL2A1 was analyzed through semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR. Results Notochordal cells were maintained in culture on PPE:N for up to 14 days with no loss in cell viability. Except for VIM, gene expression varied depending on the culture periods and [N] concentration of the substratum. Generally, PPE:N surfaces altered gene expression significantly when cells were cultured for 3 or 7 days. Conclusion The present study has shown that notochordal cells from dogs can attach to and grow on PPE:N surfaces. Analysis of the expression of different genes in these cells cultured on different N-functionalized surfaces indicates that cellular behaviour is gene-specific and time-dependent. Further studies are required to better understand the roles of specific surface functionalities on receptor sites, and their effects on cellular phenotypes.

A zebrafish model of chordoma initiated by notochord-driven expression of HRASV12

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Alexa Burger

2014-07-01

Full Text Available Chordoma is a malignant tumor thought to arise from remnants of the embryonic notochord, with its origin in the bones of the axial skeleton. Surgical resection is the standard treatment, usually in combination with radiation therapy, but neither chemotherapeutic nor targeted therapeutic approaches have demonstrated success. No animal model and only few chordoma cell lines are available for preclinical drug testing, and, although no druggable genetic drivers have been identified, activation of EGFR and downstream AKT-PI3K pathways have been described. Here, we report a zebrafish model of chordoma, based on stable transgene-driven expression of HRASV12 in notochord cells during development. Extensive intra-notochordal tumor formation is evident within days of transgene expression, ultimately leading to larval death. The zebrafish tumors share characteristics of human chordoma as demonstrated by immunohistochemistry and electron microscopy. The mTORC1 inhibitor rapamycin, which has some demonstrated activity in a chordoma cell line, delays the onset of tumor formation in our zebrafish model, and improves survival of tumor-bearing fish. Consequently, the HRASV12-driven zebrafish model of chordoma could enable high-throughput screening of potential therapeutic agents for the treatment of this refractory cancer.

The transcription factor FoxB mediates temporal loss of cellular competence for notochord induction in ascidian embryos.

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Hashimoto, Hidehiko; Enomoto, Takashi; Enomoto, Atsushi; Kumano, Gaku; Nishida, Hiroki

2011-06-01

In embryos of the ascidian Halocynthia roretzi, the competence of isolated presumptive notochord blastomeres to respond to fibroblast growth factor (FGF) for induction of the primary notochord decays by 1 hour after cleavage from the 32- to 64-cell stage. This study analyzes the molecular mechanisms responsible for this loss of competence and provides evidence for a novel mechanism. A forkhead family transcription factor, FoxB, plays a role in competence decay by preventing the induction of notochord-specific Brachyury (Bra) gene expression by the FGF/MAPK signaling pathway. Unlike the mechanisms reported previously in other animals, no component in the FGF signal transduction cascade appeared to be lost or inactivated at the time of competence loss. Knockdown of FoxB functions allowed the isolated cells to retain their competence for a longer period, and to respond to FGF with expression of Bra beyond the stage at which competence was normally lost. FoxB acts as a transcription repressor by directly binding to the cis-regulatory element of the Bra gene. Our results suggest that FoxB prevents ectopic induction of the notochord fate within the cells that assume a default nerve cord fate, after the stage when notochord induction has been completed. The merit of this system is that embryos can use the same FGF signaling cascade again for another purpose in the same cell lineage at later stages by keeping the signaling cascade itself available. Temporally and spatially regulated FoxB expression in nerve cord cells was promoted by the ZicN transcription factor and absence of FGF/MAPK signaling.

FoxA4 favours notochord formation by inhibiting contiguous mesodermal fates and restricts anterior neural development in Xenopus embryos.

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Sabrina Murgan

Full Text Available In vertebrates, the embryonic dorsal midline is a crucial signalling centre that patterns the surrounding tissues during development. Members of the FoxA subfamily of transcription factors are expressed in the structures that compose this centre. Foxa2 is essential for dorsal midline development in mammals, since knock-out mouse embryos lack a definitive node, notochord and floor plate. The related gene foxA4 is only present in amphibians. Expression begins in the blastula -chordin and -noggin expressing centre (BCNE and is later restricted to the dorsal midline derivatives of the Spemann's organiser. It was suggested that the early functions of mammalian foxa2 are carried out by foxA4 in frogs, but functional experiments were needed to test this hypothesis. Here, we show that some important dorsal midline functions of mammalian foxa2 are exerted by foxA4 in Xenopus. We provide new evidence that the latter prevents the respecification of dorsal midline precursors towards contiguous fates, inhibiting prechordal and paraxial mesoderm development in favour of the notochord. In addition, we show that foxA4 is required for the correct regionalisation and maintenance of the central nervous system. FoxA4 participates in constraining the prospective rostral forebrain territory during neural specification and is necessary for the correct segregation of the most anterior ectodermal derivatives, such as the cement gland and the pituitary anlagen. Moreover, the early expression of foxA4 in the BCNE (which contains precursors of the whole forebrain and most of the midbrain and hindbrain is directly required to restrict anterior neural development.

Diagnosing an extra-axial chordoma of the proximal tibia with the help of brachyury, a molecule required for notochordal differentiation

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O' Donnell, Paul [Royal National Orthopaedic Hospital, Department of Radiology, Stanmore, Middlesex (United Kingdom); University College London, Institute of Orthopaedics and Musculoskeletal Science, Stanmore, Middlesex (United Kingdom); Tirabosco, Roberto [Royal National Orthopaedic Hospital, Department of Histopathology, Stanmore, Middlesex (United Kingdom); Vujovic, Sonja; Henderson, Stephen; Boshoff, Chris [University College London, Wolfson Institute for Biomedical Research, London (United Kingdom); Bartlett, William; Briggs, Timothy W.R. [Royal National Orthopaedic Hospital, Department of Orthopaedic Surgery, Stanmore, Middlesex (United Kingdom); Flanagan, Adrienne M. [Royal National Orthopaedic Hospital, Department of Histopathology, Stanmore, Middlesex (United Kingdom); University College London, Institute of Orthopaedics and Musculoskeletal Science, Stanmore, Middlesex (United Kingdom)

2007-01-15

Chordomas are rare malignant bone tumours considered to arise from notochordal remnants that persist in the axial skeleton. Although their morphology can resemble that of a carcinoma, chondrosarcoma or malignant melanoma, the axial location and their well-defined immunophenotype, including expression of cytokeratins (CK7/20/8/18/19) and S100, generally allow the diagnosis to be made with confidence once the possibility is considered. In contrast, making a robust diagnosis of an extra-axial chordoma has been difficult in the absence of specific markers for chordomas. We have recently shown in gene expression microarray and immunohistochemistry studies that brachyury, a transcription factor crucial for notochordal development, is a specific and sensitive maker for chordomas. We now present a case of an intracortical tibial tumour, with detailed report of the imaging, and morphological features consistent with a chordoma, where notochordal differentiation was demonstrated with an antibody to brachyury. The tumour cells were also positive for cytokeratins, including CK19, and S100, CEA, EMA and HMBE1, findings which support the diagnosis of chordoma. Brachyury can be employed as a marker of notochordal differentiation and help identify confidently, for the first time, extra-axial bone and soft tissue chordomas, and tumours which may show focal notochordal differentiation. (orig.)

Diagnosing an extra-axial chordoma of the proximal tibia with the help of brachyury, a molecule required for notochordal differentiation

International Nuclear Information System (INIS)

O'Donnell, Paul; Tirabosco, Roberto; Vujovic, Sonja; Henderson, Stephen; Boshoff, Chris; Bartlett, William; Briggs, Timothy W.R.; Flanagan, Adrienne M.

2007-01-01

Chordomas are rare malignant bone tumours considered to arise from notochordal remnants that persist in the axial skeleton. Although their morphology can resemble that of a carcinoma, chondrosarcoma or malignant melanoma, the axial location and their well-defined immunophenotype, including expression of cytokeratins (CK7/20/8/18/19) and S100, generally allow the diagnosis to be made with confidence once the possibility is considered. In contrast, making a robust diagnosis of an extra-axial chordoma has been difficult in the absence of specific markers for chordomas. We have recently shown in gene expression microarray and immunohistochemistry studies that brachyury, a transcription factor crucial for notochordal development, is a specific and sensitive maker for chordomas. We now present a case of an intracortical tibial tumour, with detailed report of the imaging, and morphological features consistent with a chordoma, where notochordal differentiation was demonstrated with an antibody to brachyury. The tumour cells were also positive for cytokeratins, including CK19, and S100, CEA, EMA and HMBE1, findings which support the diagnosis of chordoma. Brachyury can be employed as a marker of notochordal differentiation and help identify confidently, for the first time, extra-axial bone and soft tissue chordomas, and tumours which may show focal notochordal differentiation. (orig.)

A zebrafish model of chordoma initiated by notochord-driven expression of HRASV12.

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Burger, Alexa; Vasilyev, Aleksandr; Tomar, Ritu; Selig, Martin K; Nielsen, G Petur; Peterson, Randall T; Drummond, Iain A; Haber, Daniel A

2014-07-01

Chordoma is a malignant tumor thought to arise from remnants of the embryonic notochord, with its origin in the bones of the axial skeleton. Surgical resection is the standard treatment, usually in combination with radiation therapy, but neither chemotherapeutic nor targeted therapeutic approaches have demonstrated success. No animal model and only few chordoma cell lines are available for preclinical drug testing, and, although no druggable genetic drivers have been identified, activation of EGFR and downstream AKT-PI3K pathways have been described. Here, we report a zebrafish model of chordoma, based on stable transgene-driven expression of HRASV12 in notochord cells during development. Extensive intra-notochordal tumor formation is evident within days of transgene expression, ultimately leading to larval death. The zebrafish tumors share characteristics of human chordoma as demonstrated by immunohistochemistry and electron microscopy. The mTORC1 inhibitor rapamycin, which has some demonstrated activity in a chordoma cell line, delays the onset of tumor formation in our zebrafish model, and improves survival of tumor-bearing fish. Consequently, the HRASV12-driven zebrafish model of chordoma could enable high-throughput screening of potential therapeutic agents for the treatment of this refractory cancer. © 2014. Published by The Company of Biologists Ltd.

Formation of intestinal atresias in the Fgfr2IIIb-/- mice is not associated with defects in notochord development or alterations in Shh expression.

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Reeder, Amy L; Botham, Robert A; Franco, Marta; Zaremba, Krzysztof M; Nichol, Peter F

2012-09-01

The etiology of intestinal atresia remains elusive but has been ascribed to a number of possible events including in utero vascular accidents, failure of recanalization of the intestinal lumen, and mechanical compression. Another such event that has been postulated to be a cause in atresia formation is disruption in notochord development. This hypothesis arose from clinical observations of notochord abnormalities in patients with intestinal atresias as well as abnormal notochord development observed in a pharmacologic animal model of intestinal atresia. Atresias in this model result from in utero exposure to Adriamycin, wherein notochord defects were noted in up to 80% of embryos that manifested intestinal atresias. Embryos with notochord abnormalities were observed to have ectopic expression of Sonic Hedgehog (Shh), which in turn was postulated to be causative in atresia formation. We were interested in determining whether disruptions in notochord development or Shh expression occurred in an established genetic model of intestinal atresia and used the fibroblast growth factor receptor 2IIIb homozygous mutant (Fgfr2IIIb-/-) mouse model. These embryos develop colonic atresias (100% penetrance) and duodenal atresias (42% penetrance). Wild-type and Fgfr2IIIb-/- mouse embryos were harvested at embryonic day (E) 10.5, E11.5, E12.5, and E13.5. Whole-mount in situ hybridization was performed on E10.5 embryos for Shh. Embryos at each time point were harvested and sectioned for hematoxylin-eosin staining. Sections were photographed specifically for the notochord and resulting images reconstructed in 3-D using Amira software. Colons were isolated from wild-type and Fgfr2IIIb-/- embryos at E10.5, then cultured for 48 hours in Matrigel with FGF10 in the presence or absence of exogenous Shh protein. Explants were harvested, fixed in formalin, and photographed. Fgfr2IIIb-/- mouse embryos exhibit no disruptions in Shh expression at E10.5, when the first events in atresia

Conodonts, Calcichordates and the Origin of Vertebrates

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J. Bergström

1998-01-01

Full Text Available Interpretation of early deuterostome evolution and relationships has been hampered by the lack of soft-part preservation in most groups. In addition, a recently revealed upside-down life orientation of vertebrates (the only real notoneuralians compared to other bilateral animals has been misinterpreted as evidence for a unique body design in all deuterostomes, misleading any search for relatives. Regarding echinoderms, the variety of body plans is confusing. The interpretation of some fossils with echinoderm-type calcite skeletons as “calcichordate” ancestors of chordates, however, involves a hypothetical reconstruction of an unusual body plan and a long series of hypothetical transitions. The number of necessary steps is much lower if cephalochordates (amphioxus or lancelet are derived directly from hemichordate enteropneusts. “Sensation interpretations” of fossils (Yunnanozoon, Cathaymyrus from Burgess Shale type deposits have added further confusion. Soft-part preservation of conodont animals, with V-shaped myomeres and a notochord, shows that they were segmented chordates, while probable eyes and teeth suggest that they were already on the vertebrate side. Die Interpretation früher Deuterostomia hinsichtlich ihrer Evolution und verwandtschaftlichen Beziehungen ist in den meisten Gruppen durch den Mangel an Weichkörpererhaltung sehr erschwert. Die kürzlich entdeckte Tatsache, daß Vertebraten, d. h. die einzigen echten Notoneuralia, im Gegensatz zu anderen bilateral symmetrischen Organismen eine mit ihrer ursprünglichen Oberseite nach unten gerichtete Lebensstellung einnehmen, hat zu der irrtümlichen Ansicht geführt, daß alle Deuostomia über einen im Tierreich einzigartigen Bauplan verfügen. Diese Interpretation brachte naturgemäß jede Suche nach Verwandtschaftsverhältnissen auf Abwege. Hinsichtlich der Echinodermata ist die bauplanmäßige Variation in der Tat verwirrend. Die Interpretation einiger Fossilien mit

Abnormal notochord branching is associated with foregut malformations in the adriamycin treated mouse model.

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Hajduk, Piotr; Sato, Hideaki; Puri, Prem; Murphy, Paula

2011-01-01

Oesophageal atresia (OA) and tracheooesophageal fistula (TOF) are relatively common human congenital malformations of the foregut where the oesophagus does not connect with the stomach and there is an abnormal connection between the stomach and the respiratory tract. They require immediate corrective surgery and have an impact on the future health of the individual. These abnormalities are mimicked by exposure of rat and mouse embryos in utero to the drug adriamycin. The causes of OA/TOF during human development are not known, however a number of mouse mutants where different signalling pathways are directly affected, show similar abnormalities, implicating multiple and complex signalling mechanisms. The similarities in developmental outcome seen in human infants and in the adriamycin treated mouse model underline the potential of this model to unravel the early embryological events and further our understanding of the processes disturbed, leading to such abnormalities. Here we report a systematic study of the foregut and adjacent tissues in embryos treated with adriamycin at E7 and E8 and analysed between E9 and E12, comparing morphology in 3D in 149 specimens. We describe a spectrum of 8 defects, the most common of which is ventral displacement and branching of the notochord (in 94% of embryos at E10) and a close spatial correspondence between the site of notochord branching and defects of the foregut. In addition gene expression analysis shows altered dorso-ventral foregut patterning in the vicinity of notochord branches. This study shows a number of features of the adriamycin mouse model not previously reported, implicates the notochord as a primary site of disturbance in such abnormalities and underlines the importance of the model to further address the mechanistic basis of foregut congenital abnormalities.

Localization of Proliferating Cells in the Inter-Vertebral Region of the Developing and Adult Vertebrae of Lizards in Relation to Growth and Regeneration.

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Alibardi, Lorenzo

2016-04-01

New cartilaginous tissues in lizards is formed during the regeneration of the tail or after vertebral damage. In order to understand the origin of new cartilaginous cells in the embryo and after injury of adult vertebrae we have studied the distribution of proliferating cartilaginous cells in the vertebral column of embryos and adults of the lizard Anolis lineatopus using autoradiography for H3-thymidine and light and ultrastructural immunocytochemistry for 5BrdU. Proliferating sclerotomal cells initially surround the notochord in a segmental pattern and give rise to the chondrocytes of the vertebral centrum that replace the original chordal cells. Qualitative observations show that proliferating sclerotomal cells dilute the labeling up to 13 days post-injection but a few maintain the labeling as long labeling retention cells and remain in the inter-centra and perichondrium after birth. These cells supply new chondroblasts for post-natal growth of vertebrae but can also proliferate in case of vertebral damage or tail amputation in lizards, a process that sustains tail regeneration. The lack of somitic organization in the regenerating tail impedes the re-formation of a segmental vertebral column that is instead replaced by a continuous cartilaginous tube. It is hypothesized that long labeling retaining cells might represent stem/primordial cells, and that their permanence in the inter-vertebral cartilages and the nearby perichondrium in adult lizards pre-adapt these reptiles to elicit a broad cartilage regeneration in case of injury of the vertebrae. © 2016 Wiley Periodicals, Inc.

Time-lapse analysis and mathematical characterization elucidate novel mechanisms underlying muscle morphogenesis.

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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.

Transcriptome sequencing of Atlantic salmon (Salmo salar L.) notochord prior to development of the vertebrae provides clues to regulation of positional fate, chordoblast lineage and mineralisation

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Wang, Shou; Furmanek, Tomasz; Kryvi, Harald; Krossøy, Christel; Totland, Geir Kåre; Grotmol, Sindre; Wargelius, Anna

2014-01-01

Background In teleosts such as Atlantic salmon (Salmo salar L.), segmentation and subsequent mineralisation of the notochord during embryonic stages are essential for normal vertebrae formation. However, the molecular mechanisms leading to segmentation and mineralisation of the notochord are poorly understood. The aim of this study was to identify genes/pathways acting in gradients over time and along the anterior-posterior axis during notochord segmentation and immediately prior to mineralis...

Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs

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Choi, Kyung-Suk; Harfe, Brian D.

2011-01-01

The vertebrae notochord is a transient rod-like structure that produces secreted factors that are responsible for patterning surrounding tissues. During later mouse embryogenesis, the notochord gives rise to the middle part of the intervertebral disc, called the nucleus pulposus. Currently, very little is known about the molecular mechanisms responsible for forming the intervertebral discs. Here we demonstrate that hedgehog signaling is required for formation of the intervertebral discs. Remo...

Differential temporal control of Foxa.a and Zic-r.b specifies brain versus notochord fate in the ascidian embryo.

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Ikeda, Tatsuro; Satou, Yutaka

2017-01-01

In embryos of an invertebrate chordate, Ciona intestinalis, two transcription factors, Foxa.a and Zic-r.b, are required for specification of the brain and the notochord, which are derived from distinct cell lineages. In the brain lineage, Foxa.a and Zic-r.b are expressed with no temporal overlap. In the notochord lineage, Foxa.a and Zic-r.b are expressed simultaneously. In the present study, we found that the temporally non-overlapping expression of Foxa.a and Zic-r.b in the brain lineage was regulated by three repressors: Prdm1-r.a (formerly called BZ1), Prdm1-r.b (BZ2) and Hes.a. In morphant embryos of these three repressor genes, Foxa.a expression was not terminated at the normal time, and Zic-r.b was precociously expressed. Consequently, Foxa.a and Zic-r.b were expressed simultaneously, which led to ectopic activation of Brachyury and its downstream pathways for notochord differentiation. Thus, temporal controls by transcriptional repressors are essential for specification of the two distinct fates of brain and notochord by Foxa.a and Zic-r.b Such a mechanism might enable the repeated use of a limited repertoire of transcription factors in developmental gene regulatory networks. © 2017. Published by The Company of Biologists Ltd.

Increased osmolarity and cell clustering preserve canine notochordal cell phenotype in culture

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Spillekom, S.; Smolders, L.A.; Grinwis, G.C.M.; Arkesteijn, I.T.M.; Ito, K.; Meij, B.P.; Tryfonidou, M.A.

2014-01-01

Degeneration of the intervertebral disc (IVD) is associated with a loss of notochordal cells (NCs) from the nucleus pulposus (NP) and their replacement by chondrocyte-like cells. NCs are known to maintain extracellular matrix quality and stimulate the chondrocyte-like NP cells, making NCs attractive

The notochord curvature in medaka (Oryzias latipes) embryos as a response to ultraviolet A irradiation.

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Sayed, Alaa El-Din Hamid; Mitani, Hiroshi

2016-11-01

In the present work, the destructive effects of ultraviolet A (UVA; 366nm) irradiation on the developmental stages of Japanese medaka (Oryzias latipes) are revealed in terms of hatching success, mortality rate, and morphological malformations (yolk sac edema, body curvature, fin blistering, and dwarfism). Fertilized eggs in stage 4 were exposed to 15, 30, and 60min/day UVA for 3days in replicates. Fish were staged and aged following the stages established by Iwamatsu [1]. We observed and recorded the hatching time and deformed and dead embryos continuously. The hatching time was prolonged and the deformed and dead embryos numbers were increased by UVA dose increase. At stage 40, samples from each group were fixed to investigate their morphology and histopathology. Some morphological malformations were recorded after UVA exposure in both strains. Histopathological changes were represented as different shapes of curvature in notochord with collapse. The degree of collapsation was depended on the dose and time of UVA exposure. Our findings show that exposure to UVA irradiation caused less vertebral column curvature in medaka fry. Moreover, p53-deficient embryos were more tolerant than those of wild-type (Hd-rR) Japanese medaka. This study indicated the dangerous effects of the UVA on medaka. Copyright © 2016 Elsevier B.V. All rights reserved.

Notochord-derived hedgehog is essential for tail regeneration in Xenopus tadpole.

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Taniguchi, Yuka; Watanabe, Kenji; Mochii, Makoto

2014-06-18

Appendage regeneration in amphibians is regulated by the combinatorial actions of signaling molecules. The requirement of molecules secreted from specific tissues is reflected by the observation that the whole process of regeneration can be inhibited if a certain tissue is removed from the amputated stump. Interestingly, urodeles and anurans show different tissue dependencies during tail regeneration. The spinal cord is essential for tail regeneration in urodele but not in anuran larva, whereas the notochord but not the spinal cord is essential for tail regeneration in anuran tadpoles. Sonic hedgehog is one of the signaling molecules responsible for such phenomenon in axolotl, as hedgehog signaling is essential for overall tail regeneration and sonic hedgehog is exclusively expressed in the spinal cord. In order to know whether hedgehog signaling is involved in the molecular mechanism underlying the inconsistent tissue dependency for tail regeneration between anurans and urodeles, we investigated expression of hedgehog signal-related genes in the regenerating tail of Xenopus tadpole and examined the effect of the hedgehog signal inhibitor, cyclopamine, on the tail regeneration. In Xenopus, sonic hedgehog is expressed exclusively in the notochord but not in the spinal cord of the regenerate. Overall regeneration was severely impaired in cyclopamine-treated tadpoles. Notochord maturation in the regenerate, including cell alignment and vacuolation, and myofiber formation were inhibited. Proliferation of spinal cord cells in the neural ampulla and of mesenchymal cells was also impaired. As in the axolotl, hedgehog signaling is required for multiple steps in tail regeneration in the Xenopus tadpole, although the location of the Shh source is quite different between the two species. This difference in Shh localization is the likely basis for the differing tissue requirement for tail regeneration between urodeles and anurans.

Differential gene expression in notochord and nerve cord fate segregation in the Ciona intestinalis embryo.

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Kobayashi, Kenji; Yamada, Lixy; Satou, Yutaka; Satoh, Nori

2013-09-01

During early embryogenesis, embryonic cells gradually restrict their developmental potential and are eventually destined to give rise to one type of cells. Molecular mechanisms underlying developmental fate restriction are one of the major research subjects within developmental biology. In this article, this subject was addressed by combining blastomere isolation with microarray analysis. During the 6th cleavage of the Ciona intestinalis embryo, from the 32-cell to the 64-cell stage, four mother cells divide into daughter cells with two distinct fates, one giving rise to notochord precursor cells and the other to nerve cord precursors. Approximately 2,200 each of notochord and nerve cord precursor cells were isolated, and their mRNA expression profiles were compared by microarray. This analysis identified 106 and 68 genes, respectively, that are differentially expressed in notochord and nerve cord precursor cells. These included not only genes for transcription factors and signaling molecules but also those with generalized functions observed in many types of cells. In addition, whole-mount in situ hybridization showed dynamic spatial expression profiles of these genes during segregation of the two fates: partitioning of transcripts present in the mother cells into either type of daughter cells, and initiation of preferential gene expression in either type of cells. Copyright © 2013 Wiley Periodicals, Inc.

Foxa1 and Foxa2 are required for formation of the intervertebral discs.

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Jennifer A Maier

Full Text Available The intervertebral disc (IVD is composed of 3 main structures, the collagenous annulus fibrosus (AF, which surrounds the gel-like nucleus pulposus (NP, and hyaline cartilage endplates, which are attached to the vertebral bodies. An IVD is located between each vertebral body. Degeneration of the IVD is thought to be a major cause of back pain, a potentially chronic condition for which there exist few effective treatments. The NP forms from the embryonic notochord. Foxa1 and Foxa2, transcription factors in the forkhead box family, are expressed early during notochord development. However, embryonic lethality and the absence of the notochord in Foxa2 null mice have precluded the study of potential roles these genes may play during IVD formation. Using a conditional Foxa2 allele in conjunction with a tamoxifen-inducible Cre allele (ShhcreER(T2, we removed Foxa2 from the notochord of E7.5 mice null for Foxa1. Foxa1(-/-;Foxa2(c/c;ShhcreER(T2 double mutant animals had a severely deformed nucleus pulposus, an increase in cell death in the tail, decreased hedgehog signaling, defects in the notochord sheath, and aberrant dorsal-ventral patterning of the neural tube. Embryos lacking only Foxa1 or Foxa2 from the notochord were indistinguishable from control animals, demonstrating a functional redundancy for these genes in IVD formation. In addition, we provide in vivo genetic evidence that Foxa genes are required for activation of Shh in the notochord.

Foxa1 and Foxa2 Are Required for Formation of the Intervertebral Discs

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Maier, Jennifer A.; Lo, YinTing; Harfe, Brian D.

2013-01-01

The intervertebral disc (IVD) is composed of 3 main structures, the collagenous annulus fibrosus (AF), which surrounds the gel-like nucleus pulposus (NP), and hyaline cartilage endplates, which are attached to the vertebral bodies. An IVD is located between each vertebral body. Degeneration of the IVD is thought to be a major cause of back pain, a potentially chronic condition for which there exist few effective treatments. The NP forms from the embryonic notochord. Foxa1 and Foxa2, transcription factors in the forkhead box family, are expressed early during notochord development. However, embryonic lethality and the absence of the notochord in Foxa2 null mice have precluded the study of potential roles these genes may play during IVD formation. Using a conditional Foxa2 allele in conjunction with a tamoxifen-inducible Cre allele (ShhcreERT2), we removed Foxa2 from the notochord of E7.5 mice null for Foxa1. Foxa1−/−;Foxa2c/c;ShhcreERT2 double mutant animals had a severely deformed nucleus pulposus, an increase in cell death in the tail, decreased hedgehog signaling, defects in the notochord sheath, and aberrant dorsal-ventral patterning of the neural tube. Embryos lacking only Foxa1 or Foxa2 from the notochord were indistinguishable from control animals, demonstrating a functional redundancy for these genes in IVD formation. In addition, we provide in vivo genetic evidence that Foxa genes are required for activation of Shh in the notochord. PMID:23383217

Hanging on for the ride: adhesion to the extracellular matrix mediates cellular responses in skeletal muscle morphogenesis and disease.

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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

Role of cranial neural crest cells in visceral arch muscle positioning and morphogenesis in the Mexican axolotl, Ambystoma mexicanum.

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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.

Perithecium morphogenesis in Sordaria macrospora.

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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.

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

The Stimulatory Effect of Notochordal-Cell Conditioned Medium in a Nucleus Pulposus Explant Culture

NARCIS (Netherlands)

de Vries, Stefan; Doeselaar, Marina van; Meij, Björn; Tryfonidou, M; Ito, Keita

2015-01-01

OBJECTIVES: Notochordal cell-conditioned medium (NCCM) has previously shown to have a stimulatory effect on nucleus pulposus cells (NPCs) and bone marrow stromal cells (BMSCs) in alginate and pellet cultures. These culture methods provide a different environment than the nucleus pulposus (NP)

The Stimulatory Effect of Notochordal Cell-Conditioned Medium in a Nucleus Pulposus Explant Culture

NARCIS (Netherlands)

de Vries, Stefan A H; van Doeselaar, Marina; Meij, Björn P; Tryfonidou, Marianna A; Ito, K

2016-01-01

Objectives: Notochordal cell-conditioned medium (NCCM) has previously shown to have a stimulatory effect on nucleus pulposus cells (NPCs) and bone marrow stromal cells (BMSCs) in alginate and pellet cultures. These culture methods provide a different environment than the nucleus pulposus (NP)

Copper pyrithione, a booster biocide, induces abnormal muscle and notochord architecture in zebrafish embryogenesis.

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Almond, Kelly M; Trombetta, Louis D

2017-09-01

The metal pyrithiones, principally zinc (ZnPT) and copper (CuPT), are replacing tributyltin (TBT) as antifouling agents. Zebrafish embryos were exposed within the first hour after fertilization to 12 and 64 µg/L of CuPT for 24 h. Morphological abnormalities in notochord and muscle architecture were observed at 96 h post fertilization (hpf). TEM revealed abnormal electron dense deposits in the notochord sheath and muscle fiber degeneration in animals treated with 12 µg/L of CuPT. Embryos that were exposed to 64 µg/L of CuPT displayed severe muscle fiber degeneration including abnormal A and I band patterning and altered z disk arrangement. Abnormalities in the notochord sheath, swelling of the mitochondria and numerous lipid whorls were also noted. Total antioxidant capacity was significantly decreased in embryos exposed to 12 and 64 µg/L of CuPT. Acridine orange staining revealed an increase in apoptosis particularly in the brain, eye, heart and tail regions of both treatment groups. Apoptosis was confirmed with an increase in caspase 3/7 activity in both treatment groups. Severe alternations in primary motor neuron axon extensions, slow tonic muscle fibers and fast twitch fibers were observed in CuPT treated embryos. There was a significant upregulation in sonic hedgehog and myod1 expression at 24 hpf in the 12 µg/L treatment group. Exposed zebrafish embryos showed ultra-structural hallmarks of peroxidative injury and cell death via apoptosis. These changes question the use of copper pyrithione as an antifouling agent.

The maternal genes Ci-p53/p73-a and Ci-p53/p73-b regulate zygotic ZicL expression and notochord differentiation in Ciona intestinalis embryos.

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Noda, Takeshi

2011-12-01

I isolated a Ciona intestinalis homolog of p53, Ci-p53/p73-a, in a microarray screen of rapidly degraded maternal mRNA by comparing the transcriptomes of unfertilized eggs and 32-cell stage embryos. Higher expression of the gene in eggs and lower expression in later embryonic stages were confirmed by whole-mount in situ hybridization (WISH) and quantitative reverse transcription-PCR (qRT-PCR); expression was ubiquitous in eggs and early embryos. Knockdown of Ci-p53/p73-a by injection of antisense morpholino oligonucleotides (MOs) severely perturbed gastrulation cell movements and expression of notochord marker genes. A key regulator of notochord differentiation in Ciona embryos is Brachyury (Ci-Bra), which is directly activated by a zic-like gene (Ci-ZicL). The expression of Ci-ZicL and Ci-Bra in A-line notochord precursors was downregulated in Ci-p53/p73-a knockdown embryos. Maternal expression of Ci-p53/p73-b, a homolog of Ci-p53/p73-a, was also detected. In Ci-p53/p73-b knockdown embryos, gastrulation cell movements, expression of Ci-ZicL and Ci-Bra in A-line notochord precursors, and expression of notochord marker gene at later stages were perturbed. The upstream region of Ci-ZicL contains putative p53-binding sites. Cis-regulatory analysis of Ci-ZicL showed that these sites are involved in expression of Ci-ZicL in A-line notochord precursors at the 32-cell and early gastrula stages. These results suggest that p53 genes are maternal factors that play a crucial role in A-line notochord differentiation in C. intestinalis embryos by regulating Ci-ZicL expression. Copyright © 2011 Elsevier Inc. All rights reserved.

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

Spatiotemporal analysis of putative notochordal cell markers reveals CD24 and keratins 8, 18, and 19 as notochord‐specific markers during early human intervertebral disc development

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Rodrigues‐Pinto, Ricardo; Berry, Andrew; Piper‐Hanley, Karen; Hanley, Neil; Richardson, Stephen M.

2016-01-01

ABSTRACT In humans, the nucleus pulposus (NP) is composed of large vacuolated notochordal cells in the fetus but, soon after birth, becomes populated by smaller, chondrocyte‐like cells. Although animal studies indicate that notochord‐derived cells persist in the adult NP, the ontogeny of the adult human NP cell population is still unclear. As such, identification of unique notochordal markers is required. This study was conducted to determine the spatiotemporal expression of putative human notochordal markers to aid in the elucidation of the ontogeny of adult human NP cells. Human embryos and fetuses (3.5–18 weeks post‐conception (WPC)) were microdissected to isolate the spine anlagens (notochord and somites/sclerotome). Morphology of the developing IVD was assessed using hematoxylin and eosin. Expression of keratin (KRT) 8, KRT18, KRT19, CD24, GAL3, CD55, BASP1, CTGF, T, CD90, Tie2, and E‐cadherin was assessed using immunohistochemistry. KRT8, KRT18, KRT19 were uniquely expressed by notochordal cells at all spine levels at all stages studied; CD24 was expressed at all stages except 3.5 WPC. While GAL3, CD55, BASP1, CTGF, and T were expressed by notochordal cells at specific stages, they were also co‐expressed by sclerotomal cells. CD90, Tie2, and E‐cadherin expression was not detectable in developing human spine cells at any stage. This study has identified, for the first time, the consistent expression of KRT8, KRT18, KRT19, and CD24 as human notochord‐specific markers during early IVD development. Thus, we propose that these markers can be used to help ascertain the ontogeny of adult human NP cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 34:1327–1340, 2016. PMID:26910849

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

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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.

A case of split notochord syndrome: a child with a neuroenteric fistula presenting with meningitis

NARCIS (Netherlands)

G.H. van Ramshorst (Gabrielle); M.H. Lequin (Maarten); G.M.S. Mancini (Grazia); C. van de Ven (C.)

2006-01-01

textabstractThe authors describe a case of split notochord syndrome with a neuroenteric fistula in a newborn presenting with meningitis. Associated anomalies included agenesis of the corpus callosum, short colon, malrotation, epispadias, and an abnormally high bifurcation of the abdominal aorta and

Roles for Msx and Dlx homeoproteins in vertebrate development.

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Bendall, A J; Abate-Shen, C

2000-04-18

This review provides a comparative analysis of the expression patterns, functions, and biochemical properties of Msx and Dlx homeobox genes. These comprise multi-gene families that are closely related with respect to sequence features as well as expression patterns during vertebrate development. Thus, members of the Msx and Dlx families are expressed in overlapping, but distinct, patterns and display complementary or antagonistic functions, depending upon the context. A common theme shared among Msx and Dlx genes is that they are required during early, middle, and late phases of development where their differential expression mediates patterning, morphogenesis, and histogenesis of tissues in which they are expressed. With respect to their biochemical properties, Msx proteins function as transcriptional repressors, while Dlx proteins are transcriptional activators. Moreover, their ability to oppose each other's transcriptional actions implies a mechanism underlying their complementary or antagonistic functions during development.

Brachyury Essential for Notochord Cell Fate, Not Proliferation or EMT | Center for Cancer Research

Science.gov (United States)

The Brachyury or T gene encodes a transcription factor that is essential for body axis elongation during embryonic development. T is also highly expressed in chordomas, rare sarcomas derived from notochord cells, and a number of additional tumor types, including lung, prostate, and colon cancers. 

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

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.

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.

Evolutionary origins of C-terminal (GPPn 3-hydroxyproline formation in vertebrate tendon collagen.

Directory of Open Access Journals (Sweden)

David M Hudson

Full Text Available Approximately half the proline residues in fibrillar collagen are hydroxylated. The predominant form is 4-hydroxyproline, which helps fold and stabilize the triple helix. A minor form, 3-hydroxyproline, still has no clear function. Using peptide mass spectrometry, we recently revealed several previously unknown molecular sites of 3-hydroxyproline in fibrillar collagen chains. In fibril-forming A-clade collagen chains, four new partially occupied 3-hydroxyproline sites were found (A2, A3, A4 and (GPPn in addition to the fully occupied A1 site at Pro986. The C-terminal (GPPn motif has five consecutive GPP triplets in α1(I, four in α2(I and three in α1(II, all subject to 3-hydroxylation. The evolutionary origins of this substrate sequence were investigated by surveying the pattern of its 3-hydroxyproline occupancy from early chordates through amphibians, birds and mammals. Different tissue sources of type I collagen (tendon, bone and skin and type II collagen (cartilage and notochord were examined by mass spectrometry. The (GPPn domain was found to be a major substrate for 3-hydroxylation only in vertebrate fibrillar collagens. In higher vertebrates (mouse, bovine and human, up to five 3-hydroxyproline residues per (GPPn motif were found in α1(I and four in α2(I, with an average of two residues per chain. In vertebrate type I collagen the modification exhibited clear tissue specificity, with 3-hydroxyproline prominent only in tendon. The occupancy also showed developmental changes in Achilles tendon, with increasing 3-hydroxyproline levels with age. The biological significance is unclear but the level of 3-hydroxylation at the (GPPn site appears to have increased as tendons evolved and shows both tendon type and developmental variations within a species.

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

Confocal imaging of whole vertebrate embryos reveals novel insights into molecular and cellular mechanisms of organ development

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Hadel, Diana M.; Keller, Bradley B.; Sandell, Lisa L.

2014-03-01

Confocal microscopy has been an invaluable tool for studying cellular or sub-cellular biological processes. The study of vertebrate embryology is based largely on examination of whole embryos and organs. The application of confocal microscopy to immunostained whole mount embryos, combined with three dimensional (3D) image reconstruction technologies, opens new avenues for synthesizing molecular, cellular and anatomical analysis of vertebrate development. Optical cropping of the region of interest enables visualization of structures that are morphologically complex or obscured, and solid surface rendering of fluorescent signal facilitates understanding of 3D structures. We have applied these technologies to whole mount immunostained mouse embryos to visualize developmental morphogenesis of the mammalian inner ear and heart. Using molecular markers of neuron development and transgenic reporters of neural crest cell lineage we have examined development of inner ear neurons that originate from the otic vesicle, along with the supporting glial cells that derive from the neural crest. The image analysis reveals a previously unrecognized coordinated spatial organization between migratory neural crest cells and neurons of the cochleovestibular nerve. The images also enable visualization of early cochlear spiral nerve morphogenesis relative to the developing cochlea, demonstrating a heretofore unknown association of neural crest cells with extending peripheral neurite projections. We performed similar analysis of embryonic hearts in mouse and chick, documenting the distribution of adhesion molecules during septation of the outflow tract and remodeling of aortic arches. Surface rendering of lumen space defines the morphology in a manner similar to resin injection casting and micro-CT.

Deletion of the Vaccinia Virus I2 Protein Interrupts Virion Morphogenesis, Leading to Retention of the Scaffold Protein and Mislocalization of Membrane-Associated Entry Proteins.

Science.gov (United States)

Hyun, Seong-In; Weisberg, Andrea; Moss, Bernard

2017-08-01

The I2L open reading frame of vaccinia virus (VACV) encodes a conserved 72-amino-acid protein with a putative C-terminal transmembrane domain. Previous studies with a tetracycline-inducible mutant demonstrated that I2-deficient virions are defective in cell entry. The purpose of the present study was to determine the step of replication or entry that is affected by loss of the I2 protein. Fluorescence microscopy experiments showed that I2 colocalized with a major membrane protein of immature and mature virions. We generated a cell line that constitutively expressed I2 and allowed construction of the VACV I2L deletion mutant vΔI2. As anticipated, vΔI2 was unable to replicate in cells that did not express I2. Unexpectedly, morphogenesis was interrupted at a stage after immature virion formation, resulting in the accumulation of dense spherical particles instead of brick-shaped mature virions with well-defined core structures. The abnormal particles retained the D13 scaffold protein of immature virions, were severely deficient in the transmembrane proteins that comprise the entry fusion complex (EFC), and had increased amounts of unprocessed membrane and core proteins. Total lysates of cells infected with vΔI2 also had diminished EFC proteins due to instability attributed to their hydrophobicity and failure to be inserted into viral membranes. A similar instability of EFC proteins had previously been found with unrelated mutants blocked earlier in morphogenesis that also accumulated viral membranes retaining the D13 scaffold. We concluded that I2 is required for virion morphogenesis, release of the D13 scaffold, and the association of EFC proteins with viral membranes. IMPORTANCE Poxviruses comprise a large family that infect vertebrates and invertebrates, cause disease in both in humans and in wild and domesticated animals, and are being engineered as vectors for vaccines and cancer therapy. In addition, investigations of poxviruses have provided insights into

2R and remodeling of vertebrate signal transduction engine

Directory of Open Access Journals (Sweden)

Huminiecki Lukasz

2010-12-01

Full Text Available Abstract Background Whole genome duplication (WGD is a special case of gene duplication, observed rarely in animals, whereby all genes duplicate simultaneously through polyploidisation. Two rounds of WGD (2R-WGD occurred at the base of vertebrates, giving rise to an enormous wave of genetic novelty, but a systematic analysis of functional consequences of this event has not yet been performed. Results We show that 2R-WGD affected an overwhelming majority (74% of signalling genes, in particular developmental pathways involving receptor tyrosine kinases, Wnt and transforming growth factor-β ligands, G protein-coupled receptors and the apoptosis pathway. 2R-retained genes, in contrast to tandem duplicates, were enriched in protein interaction domains and multifunctional signalling modules of Ras and mitogen-activated protein kinase cascades. 2R-WGD had a fundamental impact on the cell-cycle machinery, redefined molecular building blocks of the neuronal synapse, and was formative for vertebrate brains. We investigated 2R-associated nodes in the context of the human signalling network, as well as in an inferred ancestral pre-2R (AP2R network, and found that hubs (particularly involving negative regulation were preferentially retained, with high connectivity driving retention. Finally, microarrays and proteomics demonstrated a trend for gradual paralog expression divergence independent of the duplication mechanism, but inferred ancestral expression states suggested preferential subfunctionalisation among 2R-ohnologs (2ROs. Conclusions The 2R event left an indelible imprint on vertebrate signalling and the cell cycle. We show that 2R-WGD preferentially retained genes are associated with higher organismal complexity (for example, locomotion, nervous system, morphogenesis, while genes associated with basic cellular functions (for example, translation, replication, splicing, recombination; with the notable exception of cell cycle tended to be excluded. 2R

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.

Zinc finger protein 219-like (ZNF219L) and Sox9a regulate synuclein-γ2 (sncgb) expression in the developing notochord of zebrafish.

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Lien, Huang-Wei; Yang, Chung-Hsiang; Cheng, Chia-Hsiung; Liao, Yung-Feng; Han, Yu-San; Huang, Chang-Jen

2013-12-13

Zebrafish synuclein-γ2 (sncgb) has been reported to be expressed specifically in the notochord. However, the mechanism by which the sncgb gene promoter is regulated has not been described. In this paper, we demonstrate that Zinc finger protein 219-like (ZNF219L) and sox9a are involved in the regulation of sncgb gene expression. Furthermore, we observed that over-expression of both ZNF219L and Sox9a resulted in increased sncgb expression. In addition, ZNF219L is physically associated with Sox9a, and simultaneous morpholino knockdown of znf219L and sox9a caused a synergistic decrease of sncgb expression in the notochord. Taken together, our results reveal that coordination of ZNF219L with Sox9a is involved in the regulation of notochord-specific expression of sncgb. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Directional migration of leading-edge mesoderm generates physical forces: Implication in Xenopus notochord formation during gastrulation.

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Hara, Yusuke; Nagayama, Kazuaki; Yamamoto, Takamasa S; Matsumoto, Takeo; Suzuki, Makoto; Ueno, Naoto

2013-10-15

Gastrulation is a dynamic tissue-remodeling process occurring during early development and fundamental to the later organogenesis. It involves both chemical signals and physical factors. Although much is known about the molecular pathways involved, the roles of physical forces in regulating cellular behavior and tissue remodeling during gastrulation have just begun to be explored. Here, we characterized the force generated by the leading edge mesoderm (LEM) that migrates preceding axial mesoderm (AM), and investigated the contribution of LEM during Xenopus gastrulation. First, we constructed an assay system using micro-needle which could measure physical forces generated by the anterior migration of LEM, and estimated the absolute magnitude of the force to be 20-80nN. Second, laser ablation experiments showed that LEM could affect the force distribution in the AM (i.e. LEM adds stretch force on axial mesoderm along anterior-posterior axis). Third, migrating LEM was found to be necessary for the proper gastrulation cell movements and the establishment of organized notochord structure; a reduction of LEM migratory activity resulted in the disruption of mediolateral cell orientation and convergence in AM. Finally, we found that LEM migration cooperates with Wnt/PCP to form proper notochord. These results suggest that the force generated by the directional migration of LEM is transmitted to AM and assists the tissue organization of notochord in vivo independently of the regulation by Wnt/PCP. We propose that the LEM may have a mechanical role in aiding the AM elongation through the rearrangement of force distribution in the dorsal marginal zone. © 2013 Elsevier Inc. All rights reserved.

Influence of the neural tube/notochord complex on MyoD expression and cellular proliferation in chicken embryos

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H.J. Alves

2003-02-01

Full Text Available Important advances have been made in understanding the genetic processes that control skeletal muscle formation. Studies conducted on quails detected a delay in the myogenic program of animals selected for high growth rates. These studies have led to the hypothesis that a delay in myogenesis would allow somitic cells to proliferate longer and consequently increase the number of embryonic myoblasts. To test this hypothesis, recently segmented somites and part of the unsegmented paraxial mesoderm were separated from the neural tube/notochord complex in HH12 chicken embryos. In situ hybridization and competitive RT-PCR revealed that MyoD transcripts, which are responsible for myoblast determination, were absent in somites separated from neural tube/notochord (1.06 and 0.06 10-3 attomol MyoD/1 attomol ß-actin for control and separated somites, respectively; P<0.01. However, reapproximation of these structures allowed MyoD to be expressed in somites. Cellular proliferation was analyzed by immunohistochemical detection of incorporated BrdU, a thymidine analogue. A smaller but not significant (P = 0.27 number of proliferating cells was observed in somites that had been separated from neural tube/notochord (27 and 18 for control and separated somites, respectively. These results confirm the influence of the axial structures on MyoD activation but do not support the hypothesis that in the absence of MyoD transcripts the cellular proliferation would be maintained for a longer period of time.

Predicting vertebral bone strength by vertebral static histomorphometry

DEFF Research Database (Denmark)

Thomsen, Jesper Skovhus; Ebbesen, Ebbe Nils; Mosekilde, Lis

2002-01-01

of the entire vertebral bodies (L-2) were used for histomorphometry. The other iliac crest biopsies and the L-3 were destructively tested by compression. High correlation was found between BV/TV or Tb.Sp and vertebral bone strength (absolute value of r = 0.86 in both cases). Addition of Tb.Th significantly....... No gender-related differences were found in any of the relationships. Neither static histomorphometry nor biomechanical testing of iliac crest bone biopsies is a good predictor of vertebral bone strength.......The study investigates the relationship between static histomorphometry and bone strength of human lumbar vertebral bone. The ability of vertebral histomorphometry to predict vertebral bone strength was compared with that of vertebral densitometry, and also with histomorphometry and bone strength...

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

Programming Morphogenesis through Systems and Synthetic Biology.

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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.

Airway branching morphogenesis in three dimensional culture

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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

Wilms Tumor 1b defines a wound-specific sheath cell subpopulation associated with notochord repair

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Lopez-Baez, Juan Carlos; Zeng, Zhiqiang; Brunsdon, Hannah; Salzano, Angela; Brombin, Alessandro; Wyatt, Cameron; Rybski, Witold; Huitema, Leonie F A; Dale, Rodney M; Kawakami, Koichi; Englert, Christoph; Chandra, Tamir; Schulte-Merker, Stefan

2018-01-01

Regenerative therapy for degenerative spine disorders requires the identification of cells that can slow down and possibly reverse degenerative processes. Here, we identify an unanticipated wound-specific notochord sheath cell subpopulation that expresses Wilms Tumor (WT) 1b following injury in zebrafish. We show that localized damage leads to Wt1b expression in sheath cells, and that wt1b+cells migrate into the wound to form a stopper-like structure, likely to maintain structural integrity. Wt1b+sheath cells are distinct in expressing cartilage and vacuolar genes, and in repressing a Wt1b-p53 transcriptional programme. At the wound, wt1b+and entpd5+ cells constitute separate, tightly-associated subpopulations. Surprisingly, wt1b expression at the site of injury is maintained even into adult stages in developing vertebrae, which form in an untypical manner via a cartilage intermediate. Given that notochord cells are retained in adult intervertebral discs, the identification of novel subpopulations may have important implications for regenerative spine disorder treatments. PMID:29405914

Embryonic development of the axial column in the little skate, Leucoraja erinacea.

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Criswell, Katharine E; Coates, Michael I; Gillis, J Andrew

2017-03-01

The morphological patterns and molecular mechanisms of vertebral column development are well understood in bony fishes (osteichthyans). However, vertebral column morphology in elasmobranch chondrichthyans (e.g., sharks and skates) differs from that of osteichthyans, and its development has not been extensively studied. Here, we characterize vertebral development in an elasmobranch fish, the little skate, Leucoraja erinacea, using microCT, paraffin histology, and whole-mount skeletal preparations. Vertebral development begins with the condensation of mesenchyme, first around the notochord, and subsequently around the neural tube and caudal artery and vein. Mesenchyme surrounding the notochord differentiates into a continuous sheath of spindle-shaped cells, which forms the precursor to the mineralized areolar calcification of the centrum. Mesenchyme around the neural tube and caudal artery/vein becomes united by a population of mesenchymal cells that condenses lateral to the sheath of spindle-shaped cells, with this mesenchymal complex eventually differentiating into the hyaline cartilage of the future neural arches, hemal arches, and outer centrum. The initially continuous layers of areolar tissue and outer hyaline cartilage eventually subdivide into discrete centra and arches, with the notochord constricted in the center of each vertebra by a late-forming "inner layer" of hyaline cartilage, and by a ring of areolar calcification located medial to the outer vertebral cartilage. The vertebrae of elasmobranchs are distinct among vertebrates, both in terms of their composition (i.e., with centra consisting of up to three tissues layers-an inner cartilage layer, a calcified areolar ring, and an outer layer of hyaline cartilage), and their mode of development (i.e., the subdivision of arch and outer centrum cartilage from an initially continuous layer of hyaline cartilage). Given the evident variation in patterns of vertebral construction, broad taxon sampling, and

Adult-type myogenesis of the frog Xenopus laevis specifically suppressed by notochord cells but promoted by spinal cord cells in vitro.

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Yamane, Hitomi; Ihara, Setsunosuke; Kuroda, Masaaki; Nishikawa, Akio

2011-08-01

Larval-to-adult myogenic conversion occurs in the dorsal muscle but not in the tail muscle during Xenopus laevis metamorphosis. To know the mechanism for tail-specific suppression of adult myogenesis, response character was compared between adult myogenic cells (Ad-cells) and larval tail myogenic cells (La-cells) to a Sonic hedgehog (Shh) inhibitor, notochord (Nc) cells, and spinal cord (SC) cells in vitro. Cyclopamine, an Shh inhibitor, suppressed the differentiation of cultured Ad (but not La) cells, suggesting the significance of Shh signaling in promoting adult myogenesis. To test the possibility that Shh-producing axial elements (notochord and spinal cord) regulate adult myogenesis, Ad-cells or La-cells were co-cultured with Nc or SC cells. The results showed that differentiation of Ad-cells were strongly inhibited by Nc cells but promoted by SC cells. If Ad-cells were "separately" co-cultured with Nc cells without direct cell-cell interactions, adult differentiation was not inhibited but rather promoted, suggesting that Nc cells have two roles, one is a short-range suppression and another is a long-range promotion for adult myogenesis. Immunohistochemical analysis showed both notochord and spinal cord express the N-terminal Shh fragment throughout metamorphosis. The "spinal cord-promotion" and long-range effect by Nc cells on adult myogenesis is thus involved in Shh signaling, while the signaling concerning the short-range "Nc suppression" will be determined by future studies. Interestingly, these effects, "Nc suppression" and "SC promotion" were not observed for La-cells. Situation where the spinal cord/notochord cross-sectional ratio is quite larger in tadpole trunk than in the tail seems to contribute to trunk-specific promotion and tail-specific suppression of adult myogenesis during Xenopus metamorphosis.

Epithelial morphogenesis: the mouse eye as a model system.

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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.

Computational models of airway branching morphogenesis.

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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.

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.

Origin of the vertebrate body plan via mechanically biased conservation of regular geometrical patterns in the structure of the blastula.

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Edelman, David B; McMenamin, Mark; Sheesley, Peter; Pivar, Stuart

2016-09-01

We present a plausible account of the origin of the archetypal vertebrate bauplan. We offer a theoretical reconstruction of the geometrically regular structure of the blastula resulting from the sequential subdivision of the egg, followed by mechanical deformations of the blastula in subsequent stages of gastrulation. We suggest that the formation of the vertebrate bauplan during development, as well as fixation of its variants over the course of evolution, have been constrained and guided by global mechanical biases. Arguably, the role of such biases in directing morphology-though all but neglected in previous accounts of both development and macroevolution-is critical to any substantive explanation for the origin of the archetypal vertebrate bauplan. We surmise that the blastula inherently preserves the underlying geometry of the cuboidal array of eight cells produced by the first three cleavages that ultimately define the medial-lateral, dorsal-ventral, and anterior-posterior axes of the future body plan. Through graphical depictions, we demonstrate the formation of principal structures of the vertebrate body via mechanical deformation of predictable geometrical patterns during gastrulation. The descriptive rigor of our model is supported through comparisons with previous characterizations of the embryonic and adult vertebrate bauplane. Though speculative, the model addresses the poignant absence in the literature of any plausible account of the origin of vertebrate morphology. A robust solution to the problem of morphogenesis-currently an elusive goal-will only emerge from consideration of both top-down (e.g., the mechanical constraints and geometric properties considered here) and bottom-up (e.g., molecular and mechano-chemical) influences. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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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

Imaging morphogenesis: technological advances and biological insights.

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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.

A right-handed signalling pathway drives heart looping in vertebrates

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Ocaña, Oscar H.; Coskun, Hakan; Minguillón, Carolina; Murawala, Prayag; Tanaka, Elly M.; Galcerán, Joan; Muñoz-Chapuli, Ramón; Nieto, M. Angela

2017-01-01

The majority of animals show external bilateral symmetry, precluding the observation of multiple internal left-right (L/R) asymmetries that are fundamental for organ packaging and function1,2. In vertebrates, left identity is mediated by the left-specific Nodal-Pitx2 axis that is repressed on the right-hand side by the epithelial-mesenchymal transition (EMT) inducer Snail13,4. Despite some existing evidence3,5, it remains unclear whether an equivalent instructive pathway provides right-hand specific information to the embryo. Here we show that in zebrafish, BMP mediates the L/R asymmetric activation of another EMT inducer, Prrx1a, in the lateral plate mesoderm (LPM) with higher levels on the right. Prrx1a drives L/R differential cell movements towards the midline leading to a leftward displacement of the cardiac posterior pole through an actomyosin-dependent mechanism. Downregulation of Prrx1a prevents heart looping and leads to mesocardia. Two parallel and mutually repressed pathways, respectively driven by Nodal and BMP on the left and right LPM, converge on the asymmetric activation of Pitx2 and Prrx1, two transcription factors that integrate left and right information to govern heart morphogenesis. This mechanism is conserved in the chicken embryo and, in the mouse, Snail1 fulfills the role played by Prrx1 in fish and chick. Thus, a differential L/R EMT produces asymmetric cell movements and forces, more prominent from the right, that drive heart laterality in vertebrates. PMID:28880281

ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish.

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Ishikawa, Tokiro; Okada, Tetsuya; Ishikawa-Fujiwara, Tomoko; Todo, Takeshi; Kamei, Yasuhiro; Shigenobu, Shuji; Tanaka, Minoru; Saito, Taro L; Yoshimura, Jun; Morishita, Shinichi; Toyoda, Atsushi; Sakaki, Yoshiyuki; Taniguchi, Yoshihito; Takeda, Shunichi; Mori, Kazutoshi

2013-05-01

ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6α is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6α/β double knockout, but not ATF6α- or ATF6β single knockout, causes embryonic lethality, as in mice. Analyses of ER stress reporters reveal that ER stress occurs physiologically during medaka early embryonic development, particularly in the brain, otic vesicle, and notochord, resulting in ATF6α- and ATF6β-mediated induction of BiP, and that knockdown of the α1 chain of type VIII collagen reduces such ER stress. The absence of transcriptional induction of several ER chaperones in ATF6α/β double knockout causes more profound ER stress and impaired notochord development, which is partially rescued by overexpression of BiP. Thus ATF6α/β-mediated adjustment of chaperone levels to increased demands in the ER is essential for development of the notochord, which synthesizes and secretes large amounts of extracellular matrix proteins to serve as the body axis before formation of the vertebra.

The 'Tully monster' is a vertebrate.

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McCoy, Victoria E; Saupe, Erin E; Lamsdell, James C; Tarhan, Lidya G; McMahon, Sean; Lidgard, Scott; Mayer, Paul; Whalen, Christopher D; Soriano, Carmen; Finney, Lydia; Vogt, Stefan; Clark, Elizabeth G; Anderson, Ross P; Petermann, Holger; Locatelli, Emma R; Briggs, Derek E G

2016-04-28

Problematic fossils, extinct taxa of enigmatic morphology that cannot be assigned to a known major group, were once a major issue in palaeontology. A long-favoured solution to the 'problem of the problematica', particularly the 'weird wonders' of the Cambrian Burgess Shale, was to consider them representatives of extinct phyla. A combination of new evidence and modern approaches to phylogenetic analysis has now resolved the affinities of most of these forms. Perhaps the most notable exception is Tullimonstrum gregarium, popularly known as the Tully monster, a large soft-bodied organism from the late Carboniferous Mazon Creek biota (approximately 309-307 million years ago) of Illinois, USA, which was designated the official state fossil of Illinois in 1989. Its phylogenetic position has remained uncertain and it has been compared with nemerteans, polychaetes, gastropods, conodonts, and the stem arthropod Opabinia. Here we review the morphology of Tullimonstrum based on an analysis of more than 1,200 specimens. We find that the anterior proboscis ends in a buccal apparatus containing teeth, the eyes project laterally on a long rigid bar, and the elongate segmented body bears a caudal fin with dorsal and ventral lobes. We describe new evidence for a notochord, cartilaginous arcualia, gill pouches, articulations within the proboscis, and multiple tooth rows adjacent to the mouth. This combination of characters, supported by phylogenetic analysis, identifies Tullimonstrum as a vertebrate, and places it on the stem lineage to lampreys (Petromyzontida). In addition to increasing the known morphological disparity of extinct lampreys, a chordate affinity for T. gregarium resolves the nature of a soft-bodied fossil which has been debated for more than 50 years.

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.

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

Ciliary and non-ciliary expression and function of PACRG during vertebrate development

Directory of Open Access Journals (Sweden)

Thumberger Thomas

2012-08-01

Full Text Available Abstract Background Park2-co-regulated gene (PACRG is evolutionarily highly conserved from green algae to mammals. In Chlamydomonas and trypanosomes, the PACRG protein associates with flagella. Loss of PACRG results in shortened or absent flagella. In mouse the PACRG protein is required for spermatogenesis. The purpose of the present study was to analyze (1 the expression patterns of PACRG during vertebrate embryogenesis, and (2 whether the PACRG protein was required for left-right (LR axis specification through cilia-driven leftward flow in Xenopus laevis. Methods PACRG cDNAs were cloned and expression was analyzed during early embryonic development of Xenopus, mouse, rabbit and zebrafish. Antisense morpholino oligonucleotide (MO mediated gene knockdown was applied in Xenopus to investigate LR development at the level of tissue morphology, leftward flow and asymmetric marker gene expression, using timelapse videography, scanning electron microscopy (SEM and whole-mount in situ hybridization. Results were statistically evaluated using Wilcoxon paired and χ2 tests. Results PACRG mRNA expression was found in cells and tissues harboring cilia throughout the vertebrates. Highly localized expression was also detected in the brain. During early development, PACRG was specifically localized to epithelia where leftward flow arises, that is, the gastrocoel roof plate (GRP in Xenopus, the posterior notochord (PNC in mammals and Kupffer’s vesicle (KV in zebrafish. Besides its association with ciliary axonemes, subcellular localization of PACRG protein was found around the nucleus and in a spotty pattern in the cytoplasm. A green fluorescent protein (GFP fusion construct preferentially labeled cilia, rendering PACRG a versatile marker for live imaging. Loss-of-function in the frog resulted dose dependently in LR, neural tube closure and gastrulation defects, representing ciliary and non-ciliary functions of PACRG. Conclusions The PACRG protein is a novel

Developmental evolutionary biology of the vertebrate ear: conserving mechanoelectric transduction and developmental pathways in diverging morphologies

Science.gov (United States)

Fritzsch, B.; Beisel, K. W.; Bermingham, N. A.

2000-01-01

This brief overview shows that a start has been made to molecularly dissect vertebrate ear development and its evolutionary conservation to the development of the insect hearing organ. However, neither the patterning process of the ear nor the patterning process of insect sensory organs is sufficiently known at the moment to provide more than a first glimpse. Moreover, hardly anything is known about otocyst development of the cephalopod molluscs, another triploblast lineage that evolved complex 'ears'. We hope that the apparent conserved functional and cellular components present in the ciliated sensory neurons/hair cells will also be found in the genes required for vertebrate ear and insect sensory organ morphogenesis (Fig. 3). Likewise, we expect that homologous pre-patterning genes will soon be identified for the non-sensory cell development, which is more than a blocking of neuronal development through the Delta/Notch signaling system. Generation of the apparently unique ear could thus represent a multiplication of non-sensory cells by asymmetric and symmetric divisions as well as modification of existing patterning process by implementing novel developmental modules. In the final analysis, the vertebrate ear may come about by increasing the level of gene interactions in an already existing and highly conserved interactive cascade of bHLH genes. Since this was apparently achieved in all three lineages of triploblasts independently (Fig. 3), we now need to understand how much of the morphogenetic cascades are equally conserved across phyla to generate complex ears. The existing mutations in humans and mice may be able to point the direction of future research to understand the development of specific cell types and morphologies in the formation of complex arthropod, cephalopod, and vertebrate 'ears'.

Feedback, Lineages and Self-Organizing Morphogenesis.

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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.

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

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

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

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.

Delayed vertebral diagnosed L4 pincer vertebral fracture, L2-L3 ruptured vertebral lumbar disc hernia, L5 vertebral wedge fracture - Case report

OpenAIRE

Balasa D; Schiopu M; Tunas A; Baz R; Hancu Anca

2016-01-01

An association between delayed ruptured lumbar disc hernia, L5 vertebral wedge fracture and posttraumaticL4 pincer vertebral fracture (A2.3-AO clasification) at different levels is a very rare entity. We present the case of a 55 years old male who falled down from a bicycle. 2 months later because of intense and permanent vertebral lumbar and radicular L2 and L3 pain (Visual Scal Autologus of Pain7-8/10) the patient came to the hospital. He was diagnosed with pincer vertebral L4 fracture (A2....

The ‘Tully monster’ is a vertebrate

Science.gov (United States)

McCoy, Victoria E.; Saupe, Erin E.; Lamsdell, James C.; Tarhan, Lidya G.; McMahon, Sean; Lidgard, Scott; Mayer, Paul; Whalen, Christopher D.; Soriano, Carmen; Finney, Lydia; Vogt, Stefan; Clark, Elizabeth G.; Anderson, Ross P.; Petermann, Holger; Locatelli, Emma R.; Briggs, Derek E. G.

2016-04-01

Problematic fossils, extinct taxa of enigmatic morphology that cannot be assigned to a known major group, were once a major issue in palaeontology. A long-favoured solution to the ‘problem of the problematica’, particularly the ‘weird wonders’ of the Cambrian Burgess Shale, was to consider them representatives of extinct phyla. A combination of new evidence and modern approaches to phylogenetic analysis has now resolved the affinities of most of these forms. Perhaps the most notable exception is Tullimonstrum gregarium, popularly known as the Tully monster, a large soft-bodied organism from the late Carboniferous Mazon Creek biota (approximately 309-307 million years ago) of Illinois, USA, which was designated the official state fossil of Illinois in 1989. Its phylogenetic position has remained uncertain and it has been compared with nemerteans, polychaetes, gastropods, conodonts, and the stem arthropod Opabinia. Here we review the morphology of Tullimonstrum based on an analysis of more than 1,200 specimens. We find that the anterior proboscis ends in a buccal apparatus containing teeth, the eyes project laterally on a long rigid bar, and the elongate segmented body bears a caudal fin with dorsal and ventral lobes. We describe new evidence for a notochord, cartilaginous arcualia, gill pouches, articulations within the proboscis, and multiple tooth rows adjacent to the mouth. This combination of characters, supported by phylogenetic analysis, identifies Tullimonstrum as a vertebrate, and places it on the stem lineage to lampreys (Petromyzontida). In addition to increasing the known morphological disparity of extinct lampreys, a chordate affinity for T. gregarium resolves the nature of a soft-bodied fossil which has been debated for more than 50 years.

An Equatorial Contractile Mechanism Drives Cell Elongation but not Cell Division

Science.gov (United States)

Denker, Elsa; Bhattachan, Punit; Deng, Wei; Mathiesen, Birthe T.; Jiang, Di

2014-01-01

Cell shape changes and proliferation are two fundamental strategies for morphogenesis in animal development. During embryogenesis of the simple chordate Ciona intestinalis, elongation of individual notochord cells constitutes a crucial stage of notochord growth, which contributes to the establishment of the larval body plan. The mechanism of cell elongation is elusive. Here we show that although notochord cells do not divide, they use a cytokinesis-like actomyosin mechanism to drive cell elongation. The actomyosin network forming at the equator of each notochord cell includes phosphorylated myosin regulatory light chain, α-actinin, cofilin, tropomyosin, and talin. We demonstrate that cofilin and α-actinin are two crucial components for cell elongation. Cortical flow contributes to the assembly of the actomyosin ring. Similar to cytokinetic cells, membrane blebs that cause local contractions form at the basal cortex next to the equator and participate in force generation. We present a model in which the cooperation of equatorial actomyosin ring-based constriction and bleb-associated contractions at the basal cortex promotes cell elongation. Our results demonstrate that a cytokinesis-like contractile mechanism is co-opted in a completely different developmental scenario to achieve cell shape change instead of cell division. We discuss the occurrences of actomyosin rings aside from cell division, suggesting that circumferential contraction is an evolutionally conserved mechanism to drive cell or tissue elongation. PMID:24503569

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

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

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

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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

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

V. Terrestrial vertebrates

Science.gov (United States)

Dean Pearson; Deborah Finch

2011-01-01

Within the Interior West, terrestrial vertebrates do not represent a large number of invasive species relative to invasive weeds, aquatic vertebrates, and invertebrates. However, several invasive terrestrial vertebrate species do cause substantial economic and ecological damage in the U.S. and in this region (Pimental 2000, 2007; Bergman and others 2002; Finch and...

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.

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

CT study of vertebral metastasis: re-realization of the diagnostic role of the vertebral pedicle sign

International Nuclear Information System (INIS)

Meng Quanfei; Jiang Bo; Chen Yingming; Zhang Chaohui

2000-01-01

Objective: To investigate the essence of the vertebral pedicle sign of vertebral metastasis on plain film, and to explore the useful CT signs for the diagnosis and differential diagnosis of this tumor. Methods: The CT scans of the spine obtained in 48 patients with vertebral metastases, 19 patients with vertebral tuberculosis, and 11 with vertebral myeloma, were analyzed. The CT findings were correlated with the abnormalities seen on plain films in 34 of the 48 patients (66 vertebrae involved) with vertebral metastasis. Results: 66 vertebrae were involved in the group of metastasis. Of the 28 vertebrae whose vertebral body were completely destroyed, 15 were seen bilateral pedicles destruction; Of the 22 vertebrae with lateral destruction of the body, 16 were noticed unilateral pedicle destruction which located posterior to the involved side of the body. Of the 62 micro-metastatic foci, 56 were scattered in the vertebral body. In the 19 para-spinal soft-tissue masses of vertebral tuberculosis, 5 were noticed calcifications and 12 with postcontrast rings enhancement. The rates of vertebral pedicle destruction of vertebral metastasis and myeloma were not statistically different (X 2 = 0.03, P > 0.50). The locations of destruction of vertebral body in vertebral metastasis and myeloma had no statistical difference (X 2 = 3.52, P > 0.10), but they differed from that in tuberculosis (X 2 = 39.32, P < 0.001). The distribution of lesions within the vertebrae of metastasis and tuberculosis was similar, but was quite different from myeloma. Conclusion: The vertebral metastasis initially occurs in the vertebral body. The vertebral pedicle sign on plain film of vertebral metastasis is the outcome of the posterior invasion of the tumor in the vertebral body, which is of no differential significance for vertebral metastasis and myeloma. Para-spinal soft tissue mass, location of destruction of vertebral body, and the distribution of lesions within the vertebrae may help

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

The zebrafish tailbud contains two independent populations of midline progenitor cells that maintain long-term germ layer plasticity and differentiate in response to local signaling cues

Science.gov (United States)

Row, Richard H.; Tsotras, Steve R.; Goto, Hana; Martin, Benjamin L.

2016-01-01

Vertebrate body axis formation depends on a population of bipotential neuromesodermal cells along the posterior wall of the tailbud that make a germ layer decision after gastrulation to form spinal cord and mesoderm. Despite exhibiting germ layer plasticity, these cells never give rise to midline tissues of the notochord, floor plate and dorsal endoderm, raising the question of whether midline tissues also arise from basal posterior progenitors after gastrulation. We show in zebrafish that local posterior signals specify germ layer fate in two basal tailbud midline progenitor populations. Wnt signaling induces notochord within a population of notochord/floor plate bipotential cells through negative transcriptional regulation of sox2. Notch signaling, required for hypochord induction during gastrulation, continues to act in the tailbud to specify hypochord from a notochord/hypochord bipotential cell population. Our results lend strong support to a continuous allocation model of midline tissue formation in zebrafish, and provide an embryological basis for zebrafish and mouse bifurcated notochord phenotypes as well as the rare human congenital split notochord syndrome. We demonstrate developmental equivalency between the tailbud progenitor cell populations. Midline progenitors can be transfated from notochord to somite fate after gastrulation by ectopic expression of msgn1, a master regulator of paraxial mesoderm fate, or if transplanted into the bipotential progenitors that normally give rise to somites. Our results indicate that the entire non-epidermal posterior body is derived from discrete, basal tailbud cell populations. These cells remain receptive to extracellular cues after gastrulation and continue to make basic germ layer decisions. PMID:26674311

The ‘Tully monster’ is a vertebrate

Energy Technology Data Exchange (ETDEWEB)

McCoy, Victoria E.; Saupe, Erin E.; Lamsdell, James C.; Tarhan, Lidya G.; McMahon, Sean; Lidgard, Scott; Mayer, Paul; Whalen, Christopher D.; Soriano, Carmen; Finney, Lydia; Vogt, Stefan; Clark, Elizabeth G.; Anderson, Ross P.; Petermann, Holger; Locatelli, Emma R.; Briggs, Derek E. G.

2016-03-16

Abstract Problematic fossils, extinct taxa of enigmatic morphology that cannot be assigned to a known major group, were once a major issue in palaeontology. A long-favoured solution to the 'problem of the problematica'(1), particularly the 'weird wonders'(2) of the Cambrian Burgess Shale, was to consider them representatives of extinct phyla. A combination of new evidence and modern approaches to phylogenetic analysis has now resolved the affinities of most of these forms. Perhaps the most notable exception is Tullimonstrum gregarium(3), popularly known as the Tully monster, a large soft-bodied organism from the late Carboniferous Mazon Creek biota (approximately 309-307 million years ago) of Illinois, USA, which was designated the official state fossil of Illinois in 1989. Its phylogenetic position has remained uncertain and it has been compared with nemerteans(4,5), polychaetes(4), gastropods(4), conodonts(6), and the stem arthropod Opabinia(4). Here we review the morphology of Tullimonstrum based on an analysis of more than 1,200 specimens. We find that the anterior proboscis ends in a buccal apparatus containing teeth, the eyes project laterally on a long rigid bar, and the elongate segmented body bears a caudal fin with dorsal and ventral lobes(3-6). We describe new evidence for a notochord, cartilaginous arcualia, gill pouches, articulations within the proboscis, and multiple tooth rows adjacent to the mouth. This combination of characters, supported by phylogenetic analysis, identifies Tullimonstrum as a vertebrate, and places it on the stem lineage to lampreys (Petromyzontida). In addition to increasing the known morphological disparity of extinct lampreys(7-9), a chordate affinity for T. gregarium resolves the nature of a soft-bodied fossil which has been debated for more than 50 years

Vertebral osteomyelitis without disc involvement

Energy Technology Data Exchange (ETDEWEB)

Kamani, I.; Syed, I.; Saifuddin, A. E-mail: asaifuddin@aol.com; Green, R.; MacSweeney, F

2004-10-01

Vertebral osteomyelitis is most commonly due to pyogenic or granulomatous infection and typically results in the combined involvement of the intervertebral disc and adjacent vertebral bodies. Non-infective causes include the related conditions of chronic recurrent multifocal osteomyelitis (CRMO) and SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome. Occasionally, these conditions may present purely within the vertebral body, resulting in various combinations of vertebral marrow oedema and sclerosis, destructive lesions of the vertebral body and pathological vertebral collapse, thus mimicking neoplastic disease. This review illustrates the imaging features of vertebral osteomyelitis without disc involvement, with emphasis on magnetic resonance imaging (MRI) findings.

Live imaging-based model selection reveals periodic regulation of the stochastic G1/S phase transition in vertebrate axial development.

Directory of Open Access Journals (Sweden)

Mayu Sugiyama

2014-12-01

Full Text Available In multicellular organism development, a stochastic cellular response is observed, even when a population of cells is exposed to the same environmental conditions. Retrieving the spatiotemporal regulatory mode hidden in the heterogeneous cellular behavior is a challenging task. The G1/S transition observed in cell cycle progression is a highly stochastic process. By taking advantage of a fluorescence cell cycle indicator, Fucci technology, we aimed to unveil a hidden regulatory mode of cell cycle progression in developing zebrafish. Fluorescence live imaging of Cecyil, a zebrafish line genetically expressing Fucci, demonstrated that newly formed notochordal cells from the posterior tip of the embryonic mesoderm exhibited the red (G1 fluorescence signal in the developing notochord. Prior to their initial vacuolation, these cells showed a fluorescence color switch from red to green, indicating G1/S transitions. This G1/S transition did not occur in a synchronous manner, but rather exhibited a stochastic process, since a mixed population of red and green cells was always inserted between newly formed red (G1 notochordal cells and vacuolating green cells. We termed this mixed population of notochordal cells, the G1/S transition window. We first performed quantitative analyses of live imaging data and a numerical estimation of the probability of the G1/S transition, which demonstrated the existence of a posteriorly traveling regulatory wave of the G1/S transition window. To obtain a better understanding of this regulatory mode, we constructed a mathematical model and performed a model selection by comparing the results obtained from the models with those from the experimental data. Our analyses demonstrated that the stochastic G1/S transition window in the notochord travels posteriorly in a periodic fashion, with doubled the periodicity of the neighboring paraxial mesoderm segmentation. This approach may have implications for the characterization of

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.

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.

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.

Midterm Follow-Up of Vertebral Geometry and Remodeling of the Vertebral Bidisk Unit (VDU) After Percutaneous Vertebroplasty of Osteoporotic Vertebral Fractures

International Nuclear Information System (INIS)

Pitton, Michael Bernhard; Koch, Ulrike; Drees, Philip; Dueber, Christoph

2009-01-01

The purpose of this study was to investigate geometrical stability and preservation of height gain of vertebral bodies after percutaneous vertebroplasty during 2 years' follow-up and to elucidate the geometric remodeling process of the vertebral bidisk unit (VDU) of the affected segment. Patients with osteoporotic vertebral compression fractures with pain resistant to analgetic drugs were treated with polymethylmethacrylate vertebroplasty. Mean ± standard error cement volume was 5.1 ± 2.0 ml. Vertebral geometry was documented by sagittal and coronal reformations from multidetector computed tomography data sets: anterior, posterior, and lateral vertebral heights, end plate angles, and compression index (CI = anterior/posterior height). Additionally, the VDU (vertebral bodies plus both adjacent disk spaces) was calculated from the multidetector computed tomography data sets: anterior, posterior, and both lateral aspects. Patients were assigned to two groups: moderate compression with CI of >0.75 (group 1) and severe compression with CI of o vs. -1.0 ± 2.7 o , P o , P < 0.01) and compression indices (+0.11 ± 0.15, P < 0.01). Thus, posterior height loss of vertebrae and adjacent intervertebral disk spaces contributed to a remodeling of the VDU, resulting in some compensation of the kyphotic malposition of the affected vertebral segment. Vertebroplasty improved vertebral geometry during midterm follow-up. In severe vertebral compression, significant height gain and improvement of end plate angles were achieved. The remodeling of the VDUs contributes to reduction of kyphosis and an overall improvement of the statics of the spine.

Fusaric acid induces a notochord malformation in zebrafish via copper chelation.

Science.gov (United States)

Yin, Emily S; Rakhmankulova, Malika; Kucera, Kaury; de Sena Filho, Jose Guedes; Portero, Carolina E; Narváez-Trujillo, Alexandra; Holley, Scott A; Strobel, Scott A

2015-08-01

Over a thousand extracts were tested for phenotypic effects in developing zebrafish embryos to identify bioactive molecules produced by endophytic fungi. One extract isolated from Fusarium sp., a widely distributed fungal genus found in soil and often associated with plants, induced an undulated notochord in developing zebrafish embryos. The active compound was isolated and identified as fusaric acid. Previous literature has shown this phenotype to be associated with copper chelation from the active site of lysyl oxidase, but the ability of fusaric acid to bind copper ions has not been well described. Isothermal titration calorimetry revealed that fusaric acid is a modest copper chelator with a binding constant of 4.4 × 10(5) M(-1). These results shed light on the toxicity of fusaric acid and the potential teratogenic effects of consuming plants infected with Fusarium sp.

Molecular Therapy for Degenerative Disc Disease: Clues from Secretome Analysis of the Notochordal Cell-Rich Nucleus Pulposus

Science.gov (United States)

Matta, Ajay; Karim, M. Zia; Isenman, David E.; Erwin, W. Mark

2017-01-01

Degenerative disc disease (DDD) is associated with spinal pain often leading to long-term disability. However, the non-chondrodystrophic canine intervertebral disc is protected from the development of DDD, ostensibly due to its retention of notochordal cells (NC) in the nucleus pulposus (NP). In this study, we hypothesized that secretome analysis of the NC-rich NP will lead to the identification of key proteins that delay the onset of DDD. Using mass-spectrometry, we identified 303 proteins including components of TGFβ- and Wnt-signaling, anti-angiogeneic factors and proteins that inhibit axonal ingrowth in the bioactive fractions of serum free, notochordal cell derived conditioned medium (NCCM). Ingenuity Pathway Analysis revealed TGFβ1 and CTGF as major hubs in protein interaction networks. In vitro treatment with TGFβ1 and CTGF promoted the synthesis of healthy extra-cellular matrix proteins, increased cell proliferation and reduced cell death in human degenerative disc NP cells. A single intra-discal injection of recombinant TGFβ1 and CTGF proteins in a pre-clinical rat-tail disc injury model restored the NC and stem cell rich NP. In conclusion, we demonstrate the potential of TGFβ1 and CTGF to mitigate the progression of disc degeneration and the potential use of these molecules in a molecular therapy to treat the degenerative disc. PMID:28358123

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.

Delayed vertebral diagnosed L4 pincer vertebral fracture, L2-L3 ruptured vertebral lumbar disc hernia, L5 vertebral wedge fracture - Case report

Directory of Open Access Journals (Sweden)

Balasa D

2016-08-01

Full Text Available An association between delayed ruptured lumbar disc hernia, L5 vertebral wedge fracture and posttraumaticL4 pincer vertebral fracture (A2.3-AO clasification at different levels is a very rare entity. We present the case of a 55 years old male who falled down from a bicycle. 2 months later because of intense and permanent vertebral lumbar and radicular L2 and L3 pain (Visual Scal Autologus of Pain7-8/10 the patient came to the hospital. He was diagnosed with pincer vertebral L4 fracture (A2.3-AO clasification and L2-L3 right ruptured lumbar disc hernia in lateral reces. The patient was operated (L2-L3 right fenestration, and resection of lumbar disc hernia, bilateral stabilisation, L3-L4-L5 with titan screws and postero-lateral bone graft L4 bilateral harvested from iliac crest.

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

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....

Síndrome do notocórdio fendido, variante rara do cisto neuroentérico A rare variant of neuroenteric cyst: split notochord syndrome

Directory of Open Access Journals (Sweden)

Lisieux E Jesus

2004-02-01

Full Text Available OBJETIVO: Estudo de um caso de síndrome do notocórdio fendido, forma extremamente rara de disrafismo medular. A literatura pertinente, pesquisada através das bases de dados MEDLINE e LILACS, é analisada e sumarizada. DESCRIÇÃO: Foi atendido lactente masculino de 2 meses de idade apresentando extensa deformidade de coluna lombo-sacra, hidrocefalia e exteriorização de alças intestinais pela linha média dorsal, acompanhada de fístula entérica e imperfuração anal. A malformação foi diagnosticada como síndrome do notocórdio fendido. A criança evoluiu para óbito secundário a sepse antes de ser feito qualquer tratamento cirúrgico. COMENTÁRIOS: A síndrome do notocórdio fendido é a forma mais rara de cisto neuroentérico já descrita (OBJECTIVE: We present a case of split notochord syndrome, an extremely rare form of spinal dysraphism. DESCRIPTION: We treated a 2 month-old boy presenting with an extensive lumbosacral deformity, hydrocephalus and apparent enteric segments in the dorsal midline, accompanied by an enteric fistula and imperforated anus. The malformation was diagnosed as split notochord syndrome. The baby died as a result of sepsis before surgical treatment could be attempted. COMMENTS: Split notochord syndrome is the rarest form of neuroenteric cyst described until this moment (< 25 cases in the literature. It is frequently associated with anorectal malformation, intestinal fistulae and hydrocephalus. Prognosis is not necessarily poor and survival is possible if digestive malformations, hydrocephalus and the dysraphism itself are treated simultaneously.

Imaging the vertebral artery

Energy Technology Data Exchange (ETDEWEB)

Tay, Keng Yeow; U-King-Im, Jean Marie; Trivedi, Rikin A.; Higgins, Nicholas J.; Cross, Justin J.; Antoun, Nagui M. [Addenbrooke' s Hospital and University of Cambridge, Department of Radiology, Cambridge (United Kingdom); Davies, John R.; Weissberg, Peter L. [Addenbrooke' s Hospital and University of Cambridge, Division of Cardiovascular Medicine, Cambridge (United Kingdom); Gillard, Jonathan H. [Addenbrooke' s Hospital and University of Cambridge, Department of Radiology, Cambridge (United Kingdom); Addenbrooke' s Hospitald, University Department of Radiology, Cambridge (United Kingdom)

2005-07-01

Although conventional intraarterial digital subtraction angiography remains the gold standard method for imaging the vertebral artery, noninvasive modalities such as ultrasound, multislice computed tomographic angiography and magnetic resonance angiography are constantly improving and are playing an increasingly important role in diagnosing vertebral artery pathology in clinical practice. This paper reviews the current state of vertebral artery imaging from an evidence-based perspective. Normal anatomy, normal variants and a number of pathological entities such as vertebral atherosclerosis, arterial dissection, arteriovenous fistula, subclavian steal syndrome and vertebrobasilar dolichoectasia are discussed. (orig.)

Imaging the vertebral artery

International Nuclear Information System (INIS)

Tay, Keng Yeow; U-King-Im, Jean Marie; Trivedi, Rikin A.; Higgins, Nicholas J.; Cross, Justin J.; Antoun, Nagui M.; Davies, John R.; Weissberg, Peter L.; Gillard, Jonathan H.

2005-01-01

Although conventional intraarterial digital subtraction angiography remains the gold standard method for imaging the vertebral artery, noninvasive modalities such as ultrasound, multislice computed tomographic angiography and magnetic resonance angiography are constantly improving and are playing an increasingly important role in diagnosing vertebral artery pathology in clinical practice. This paper reviews the current state of vertebral artery imaging from an evidence-based perspective. Normal anatomy, normal variants and a number of pathological entities such as vertebral atherosclerosis, arterial dissection, arteriovenous fistula, subclavian steal syndrome and vertebrobasilar dolichoectasia are discussed. (orig.)

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

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.

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.

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.

Management of osteoporotic vertebral fractures

OpenAIRE

Dionyssiotis, Yannis

2010-01-01

Yannis DionyssiotisRhodes General Hospital, Rhodes, GreeceAbstract: Osteoporotic vertebral fractures are associated with considerable reduction of quality of life, morbidity, and mortality. The management of patients with vertebral fractures should include treatment for osteoporosis and measures to reduce pain and improve mobility. This article provides information for management and rehabilitation of vertebral fractures based on clinical experience and literature.Keywords: vertebral fracture...

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.

Anthropometric measurements and vertebral deformities. European Vertebral Osteoporosis Study (EVOS) Group.

Science.gov (United States)

Johnell, O; O'Neill, T; Felsenberg, D; Kanis, J; Cooper, C; Silman, A J

1997-08-15

To investigate the association between anthropometric indices and morphometrically determined vertebral deformity, the authors carried out a cross-sectional study using data from the European Vertebral Osteoporosis Study (EVOS), a population-based study of vertebral osteoporosis in 36 European centers from 19 countries. A total of 16,047 EVOS subjects were included in this analysis, of whom 1,973 subjects (915 males, 1,058 females) (12.3%) aged 50 years or over had one or more vertebral deformities ("cases"). The cases were compared with the 14,074 subjects (6,539 males, 7,535 females) with morphometrically normal spines ("controls"). Data were collected on self-reported height at age 25 years and minimum weight after age 25 years, as well as on current measured height and weight. Body mass index (BMI) and height and weight change were calculated from these data. The relations between these variables and vertebral deformity were examined separately by sex with logistic regression adjusting for age, smoking, and physical activity. In females, there was a significant trend of decreasing risk with increasing quintile of current weight, current BMI, and weight gain since age 25 years. In males, subjects in the lightest quintile for these measures were at increased risk but there was no evidence of a trend. An ecologic analysis by country revealed a negative correlation between mean BMI and the prevalence of deformity in females but not in males. The authors conclude that low body weight is associated with presence of vertebral deformity.

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.

Evolution and development of the vertebrate ear

Science.gov (United States)

Fritzsch, B.; Beisel, K. W.

2001-01-01

This review outlines major aspects of development and evolution of the ear, specifically addressing issues of cell fate commitment and the emerging molecular governance of these decisions. Available data support the notion of homology of subsets of mechanosensors across phyla (proprioreceptive mechanosensory neurons in insects, hair cells in vertebrates). It is argued that this conservation is primarily related to the specific transducing environment needed to achieve mechanosensation. Achieving this requires highly conserved transcription factors that regulate the expression of the relevant structural genes for mechanosensory transduction. While conserved at the level of some cell fate assignment genes (atonal and its mammalian homologue), the ear has also radically reorganized its development by implementing genes used for cell fate assignment in other parts of the developing nervous systems (e.g., neurogenin 1) and by evolving novel sets of genes specifically associated with the novel formation of sensory neurons that contact hair cells (neurotrophins and their receptors). Numerous genes have been identified that regulate morphogenesis, but there is only one common feature that emerges at the moment: the ear appears to have co-opted genes from a large variety of other parts of the developing body (forebrain, limbs, kidneys) and establishes, in combination with existing transcription factors, an environment in which those genes govern novel, ear-related morphogenetic aspects. The ear thus represents a unique mix of highly conserved developmental elements combined with co-opted and newly evolved developmental elements.

Height gain of vertebral bodies and stabilization of vertebral geometry over one year after vertebroplasty of osteoporotic vertebral fractures

International Nuclear Information System (INIS)

Pitton, Michael B.; Morgen, Nadine; Herber, Sascha; Dueber, Christoph; Drees, Philipp; Boehm, Bertram

2008-01-01

The height gain of vertebral bodies after vertebroplasty and geometrical stability was evaluated over a one-year period. Osteoporotic fractures were treated with vertebroplasty. The vertebral geometry and disc spaces were analysed using reformatted computed tomography (CT) images: heights of the anterior, posterior, and lateral vertebral walls, disc spaces, endplate angles, and minimal endplate distances. Vertebrae were assigned to group I [severe compression (anterior height/posterior height) 0.75). A total of 102 vertebral bodies in 40 patients (12 men, 28 women, age 70.3 ± 9.5) were treated with vertebroplasty and prospectively followed for 12 months. Group I showed a greater benefit compared with group II with respect to anterior height gain (+2.1 ± 1.9 vs +0.7 ± 1.6 mm, P < 0.001), reduction of endplate angle (-3.6 ± 4.2 vs -0.8 ± 2.3 , P < 0.001), and compression index (+0.09 ± 0.11 vs +0.01 ± 0.06, P < 0.001). At one-year follow-up, group I demonstrated preserved anterior height gain (+1.5 ± 2.8 mm, P < 0.015) and improved endplate angle (-3.4 ± 4.9 , P < 0.001). In group II, the vertebral heights returned to and were fixed at the pre-interventional levels. Vertebroplasty provided vertebral height gain over one year, particularly in cases with severe compression. Vertebrae with moderate compression were fixed and stabilized at the pre-treatment level over one year. (orig.)

Evolution of endothelin receptors in vertebrates.

Science.gov (United States)

Braasch, Ingo; Schartl, Manfred

2014-12-01

Endothelin receptors are G protein coupled receptors (GPCRs) of the β-group of rhodopsin receptors that bind to endothelin ligands, which are 21 amino acid long peptides derived from longer prepro-endothelin precursors. The most basal Ednr-like GPCR is found outside vertebrates in the cephalochordate amphioxus, but endothelin ligands are only present among vertebrates, including the lineages of jawless vertebrates (lampreys and hagfishes), cartilaginous vertebrates (sharks, rays, and chimaeras), and bony vertebrates (ray-finned fishes and lobe-finned vertebrates including tetrapods). A bona fide endothelin system is thus a vertebrate-specific innovation with important roles for regulating the cardiovascular system, renal and pulmonary processes, as well as for the development of the vertebrate-specific neural crest cell population and its derivatives. Expectedly, dysregulation of endothelin receptors and the endothelin system leads to a multitude of human diseases. Despite the importance of different types of endothelin receptors for vertebrate development and physiology, current knowledge on endothelin ligand-receptor interactions, on the expression of endothelin receptors and their ligands, and on the functional roles of the endothelin system for embryonic development and in adult vertebrates is very much biased towards amniote vertebrates. Recent analyses from a variety of vertebrate lineages, however, have shown that the endothelin system in lineages such as teleost fish and lampreys is more diverse and is divergent from the mammalian endothelin system. This diversity is mainly based on differential evolution of numerous endothelin system components among vertebrate lineages generated by two rounds of whole genome duplication (three in teleosts) during vertebrate evolution. Here we review current understanding of the evolutionary history of the endothelin receptor family in vertebrates supplemented with surveys on the endothelin receptor gene complement of

Vertebral stabilization using positively threaded profile pins and polymethylmethacrylate, with or without laminectomy, for spinal canal stenosis and vertebral instability caused by congenital thoracic vertebral anomalies.

Science.gov (United States)

Aikawa, Takeshi; Kanazono, Shinichi; Yoshigae, Yuki; Sharp, Nicholas J H; Muñana, Karen R

2007-07-01

To describe diagnostic findings, surgical technique, and outcome in dogs with thoracic spinal canal stenosis and vertebral instability secondary to congenital vertebral anomalies. Retrospective clinical study. Dogs (n=9) with thoracic spinal canal stenosis. Medical records (1995-1996; 2000-2006) of 9 dogs with a myelographic diagnosis of spinal canal stenosis and/or vertebral instability secondary to congenital vertebral anomaly that were surgically managed by vertebral stabilization with or without laminectomy were reviewed. Data on pre- and postoperative neurologic status, diagnostic findings, surgical techniques, and outcomes were retrieved. Follow-up evaluations were performed at 1, 2, and 6 months. Long-term outcome was assessed by means of clinical examination or owner telephone interviews. Spinal cord compression was confirmed by myelography, and in 2 dogs, dynamic compression by stress myelography. Eight dogs regained the ability to ambulate postoperatively. One dog with a partial recovery regained voluntary movement but did not become ambulatory. Spinal cord injury secondary to congenital vertebral anomaly may have a good outcome when treated by vertebral stabilization with or without laminectomy. Adequate stabilization of the vertebrae and improved neurologic outcome were achieved in most dogs. Vertebral stabilization using positively threaded profile pins and polymethylmethacrylate with or without laminectomy is an effective treatment for spinal canal stenosis and vertebral instability secondary to congenital thoracic vertebral anomalies.

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

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

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.

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.

The shape of the human lumbar vertebral canal A forma do canal vertebral lombar humano

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Edmundo Zarzur

1996-09-01

Full Text Available Literature on the anatomy of the human vertebral column characterizes the shape of the lumbar vertebral canal as triangular. The purpose of the present study was to determine the precise shape of the lumbar vertebral canal. Ten lumbar vertebral columns of adult male cadavers were dissected. Two transverse sections were performed in the third lumbar vertebra. One section was performed at the level of the lower border of the ligamenta flava, and the other section was performed at the level of the pedicles. The shape of the lumbar vertebral canal at the level of the pedicles tends to be oval or circular, whereas the shape of the lumbar vertebral canal at the level of the lower border of the ligamenta flava is triangular. Thus, the shape of the human lumbar vertebral canal is not exclusively triangular, as reported in the literature. It is related to the level of the transversal section performed on the lumbar vertebra. This finding should be taken into consideration among factors involved in the spread of solutions introduced into the epidural space.A literatura sobre a anatomia da coluna vertebral descreve como sendo triangular o formato do canal vertebral na região lombar. O objetivo deste estudo é determinar a real forma do canal da coluna vertebral lombar.Dez colunas vertebrais de cadáveres de homens adultos foram dissecadas. Dois cortes transversais foram executados na terceira vértebra lombar. Um corte foi feito no nível das bordas inferiores de dois ligamentos amarelos vizinhos e o outro corte foi transversal, no nível dos pedículos. A forma do canal vertebral variou: no nível dos pedículos ela tende a ser oval ou circular e junto às bordas inferiores dos ligamentos amarelos passa a ser triangular. Portanto, a forma do canal vertebral lombar não é somente triangular; ela depende do nível em que se faz o corte transversal da vértebra. Estes achados devem ser levados em consideração entre os fatores envolvidos na difusão das

Larval development of Etropus longimanus (Paralichthyidae and Symphurus trewavasae (Cynoglossidae off the Buenos Aires coast, Argentina

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Carla Derisio

2011-11-01

Full Text Available The larval development of Etropus longimanus and Symphurus trewavasae (Pleuronectiformes off the Buenos Aires coast was described. Both species have an elongated body; however, as the total length of Etropus longimanus larvae increased, their body became deeper. In Symphurus trewavasae the intestine was noticeably coiled. In E. longimanus the notochord flexion started at 3.9 mm and was completed at 5.0 mm standard length (SL. Vertebral formation began in larvae with a 4.6 mm SL and the definitive number of vertebrae (34-39 was observed in larvae of 4.8 mm SL. The dorsal fin had two elongated rays and the pelvic fins had only one. In Symphurus trewavasae the notochord flexion began at 5.9 mm and was completed at 8.0 mm SL. Migration of the right eye was completed in the metamorphic stage at 10.5 mm SL. Vertebral column ossification finished in flexion larvae of 6-7 mm SL, with a total number of 48-50 vertebrae. Four elongated rays of similar length were observed on the dorsal fin.

Primary extracranial vertebral artery aneurysms.

Science.gov (United States)

Morasch, Mark D; Phade, Sachin V; Naughton, Peter; Garcia-Toca, Manuel; Escobar, Guillermo; Berguer, Ramon

2013-05-01

Extracranial vertebral artery aneurysms are uncommon and are usually associated with trauma or dissection. Primary cervical vertebral aneurysms are even rarer and are not well described. The presentation and natural history are unknown and operative management can be difficult. Accessing aneurysms at the skull base can be difficult and, because the frail arteries are often afflicted with connective tissue abnormalities, direct repair can be particularly challenging. We describe the presentation and surgical management of patients with primary extracranial vertebral artery aneurysms. In this study we performed a retrospective, multi-institutional review of patients with primary aneurysms within the extracranial vertebral artery. Between January 2000 and January 2011, 7 patients, aged 12-56 years, were noted to have 9 primary extracranial vertebral artery aneurysms. All had underlying connective tissue or another hereditary disorder, including Ehler-Danlos syndrome (n=3), Marfan's disease (n=2), neurofibromatosis (n=1), and an unspecified connective tissue abnormality (n=1). Eight of 9 aneurysms were managed operatively, including an attempted bypass that ultimately required vertebral ligation; the contralateral aneurysm on this patient has not been treated. Open interventions included vertebral bypass with vein, external carotid autograft, and vertebral transposition to the internal carotid artery. Special techniques were used for handling the anastomoses in patients with Ehler-Danlos syndrome. Although endovascular exclusion was not performed in isolation, 2 hybrid procedures were performed. There were no instances of perioperative stroke or death. Primary extracranial vertebral artery aneurysms are rare and occur in patients with hereditary disorders. Operative intervention is warranted in symptomatic patients. Exclusion and reconstruction may be performed with open and hybrid techniques with low morbidity and mortality. Copyright © 2013 Elsevier Inc. All rights

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

Measurements of vertebral shape by radiographic morphometry: sex differences and relationships with vertebral level and lumbar lordosis

Energy Technology Data Exchange (ETDEWEB)

Cheng, X G; Sun, Y; Boonen, S; Nicholson, P H.F.; Dequeker, J [Arthritis and Metabolic Bone Disease Research Unit, U.Z. Pellenberg, Division of Rheumatology, Pellenberg (Belgium); Brys, P [Radiology Department, University Hospitals, Katholieke Universiteit Leuven, Leuven (Belgium); Felsenberg, D [Radiology Department, Freie Univ. Berlin (Germany)

1998-07-01

Objective. To examine sex-related and vertebral-level-specific differences in vertebral shape and to investigate the relationships between the lumbar lordosis angle and vertebral morphology. Design and patients. Lateral thoracic and lumbar spine radiographs were obtained with a standardized protocol in 142 healthy men and 198 healthy women over 50 years old. Anterior (Ha), central (Hc) and posterior (Hp) heights of each vertebra from T4 to L4 were measured using a digitizing technique, and the Ha/Hp and Hc/Hp ratios were calculated. The lumbar lordosis angle was measured on the lateral lumbar spine radiographs. Results. Ha/Hp and Hc/Hp ratios were smaller in men than women by 1.8% and 0.7%, respectively, and these ratios varied with vertebral level. Significant correlations were found between vertebral shape and the lumbar lordosis angle. Conclusions. These results demonstrate that vertebral shape varies significantly with sex, vertebral level and lumbar lordosis angle. Awareness of these relationships may help prevent misdiagnosis in clinical vertebral morphometry. (orig.) With 4 figs., 2 tabs., 17 refs.

Constrained vertebrate evolution by pleiotropic genes

DEFF Research Database (Denmark)

Hu, Haiyang; Uesaka, Masahiro; Guo, Song

2017-01-01

applied to vertebrates than chordates. Furthermore, we found that vertebrates' conserved mid-embryonic developmental programmes are intensively recruited to other developmental processes, and the degree of the recruitment positively correlates with their evolutionary conservation and essentiality...... for normal development. Thus, we propose that the intensively recruited genetic system during vertebrates' organogenesis period imposed constraints on its diversification through pleiotropic constraints, which ultimately led to the common anatomical pattern observed in vertebrates....

Rapid onset aggressive vertebral haemangioma.

Science.gov (United States)

Cheung, Nicholas K; Doorenbosch, Xenia; Christie, John G

2011-03-01

Vertebral haemangiomas are generally benign asymptomatic vascular tumours seen commonly in the adult population. Presentations in paediatric populations are extremely rare, which can result in rapid onset of neurological symptoms. We present a highly unusual case of an aggressive paediatric vertebral haemangioma causing significant cord compression. A 13-year-old boy presented with only 2 weeks duration of progressive gait disturbance, truncal ataxia and loss of bladder control. Magnetic resonance imaging (MRI) of the spine revealed a large vascular epidural mass extending between T6 and T8 vertebral bodies. Associated displacement and compression of the spinal cord was present. A highly vascular bony lesion was found during surgery. Histopathology identified this tumour to be a vertebral haemangioma. We present an extremely unusual acute presentation of a paediatric vertebral haemangioma. This study highlights the need for early diagnosis, MRI for investigation and urgent surgical management. © Springer-Verlag 2011

The notochord breaks bilateral symmetry by controlling cell shapes in the zebrafish laterality organ.

Science.gov (United States)

Compagnon, Julien; Barone, Vanessa; Rajshekar, Srivarsha; Kottmeier, Rita; Pranjic-Ferscha, Kornelija; Behrndt, Martin; Heisenberg, Carl-Philipp

2014-12-22

Kupffer's vesicle (KV) is the zebrafish organ of laterality, patterning the embryo along its left-right (LR) axis. Regional differences in cell shape within the lumen-lining KV epithelium are essential for its LR patterning function. However, the processes by which KV cells acquire their characteristic shapes are largely unknown. Here, we show that the notochord induces regional differences in cell shape within KV by triggering extracellular matrix (ECM) accumulation adjacent to anterior-dorsal (AD) regions of KV. This localized ECM deposition restricts apical expansion of lumen-lining epithelial cells in AD regions of KV during lumen growth. Our study provides mechanistic insight into the processes by which KV translates global embryonic patterning into regional cell shape differences required for its LR symmetry-breaking function. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

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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

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

Cement Leakage in Percutaneous Vertebral Augmentation for Osteoporotic Vertebral Compression Fractures: Analysis of Risk Factors.

Science.gov (United States)

Xie, Weixing; Jin, Daxiang; Ma, Hui; Ding, Jinyong; Xu, Jixi; Zhang, Shuncong; Liang, De

2016-05-01

The risk factors for cement leakage were retrospectively reviewed in 192 patients who underwent percutaneous vertebral augmentation (PVA). To discuss the factors related to the cement leakage in PVA procedure for the treatment of osteoporotic vertebral compression fractures. PVA is widely applied for the treatment of osteoporotic vertebral fractures. Cement leakage is a major complication of this procedure. The risk factors for cement leakage were controversial. A retrospective review of 192 patients who underwent PVA was conducted. The following data were recorded: age, sex, bone density, number of fractured vertebrae before surgery, number of treated vertebrae, severity of the treated vertebrae, operative approach, volume of injected bone cement, preoperative vertebral compression ratio, preoperative local kyphosis angle, intraosseous clefts, preoperative vertebral cortical bone defect, and ratio and type of cement leakage. To study the correlation between each factor and cement leakage ratio, bivariate regression analysis was employed to perform univariate analysis, whereas multivariate linear regression analysis was employed to perform multivariate analysis. The study included 192 patients (282 treated vertebrae), and cement leakage occurred in 100 vertebrae (35.46%). The vertebrae with preoperative cortical bone defects generally exhibited higher cement leakage ratio, and the leakage is typically type C. Vertebrae with intact cortical bones before the procedure tend to experience type S leakage. Univariate analysis showed that patient age, bone density, number of fractured vertebrae before surgery, and vertebral cortical bone were associated with cement leakage ratio (Pcement leakage are bone density and vertebral cortical bone defect, with standardized partial regression coefficients of -0.085 and 0.144, respectively. High bone density and vertebral cortical bone defect are independent risk factors associated with bone cement leakage.

Measurements of vertebral shape by r[iographic morphometry: sex differences and relationships with vertebral level and lumbar lordosis

International Nuclear Information System (INIS)

Cheng, X.G.; Sun, Y.; Boonen, S.; Nicholson, P.H.F.; Dequeker, J.; Brys, P.; Felsenberg, D.

1998-01-01

Objective. To examine sex-related and vertebral-level-specific differences in vertebral shape and to investigate the relationships between the lumbar lordosis angle and vertebral morphology. Design and patients. Lateral thoracic and lumbar spine r[iographs were obtained with a standardized protocol in 142 healthy men and 198 healthy women over 50 years old. Anterior (Ha), central (Hc) and posterior (Hp) heights of each vertebra from T4 to L4 were measured using a digitizing technique, and the Ha/Hp and Hc/Hp ratios were calculated. The lumbar lordosis angle was measured on the lateral lumbar spine r[iographs. Results. Ha/Hp and Hc/Hp ratios were smaller in men than women by 1.8% and 0.7%, respectively, and these ratios varied with vertebral level. Significant correlations were found between vertebral shape and the lumbar lordosis angle. Conclusions. These results demonstrate that vertebral shape varies significantly with sex, vertebral level and lumbar lordosis angle. Awareness of these relationships may help prevent misdiagnosis in clinical vertebral morphometry. (orig.)

ANOMALOUS PREVERTEBRAL COURSE OF THE LEFT VERTEBRAL ARTERY. Recorrido prevertebral anómalo de la arteria vertebral izquierda

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Prakash B Billakanti

2016-03-01

Full Text Available La arteria vertebral es una de las arterias que irriga el cerebro. El conocimiento de la anatomía normal y las variantes de la arteria vertebral adquiere importancia en la práctica clínica y la radiología vascular. El origen anómalo de la arteria vertebral del arco de la aorta o cualquiera de las arterias del cuello ha sido reportado por muchos autores. En este informe se presenta una variación del curso prevertebral de la arteria vertebral izquierda. La arteria vertebral tenía su origen habitual en la arteria subclavia con un largo curso prevertebral y entraba en el foramen transversarium de la vértebra CII. El origen y recorrido de la arteria vertebral en el lado derecho fue normal. Clínicamente es importante conocer el origen y curso del segmento prevertebral de la arteria vertebral y las posibles variaciones. El presente informe debería ser de interés para el médico vascular con respecto a las variaciones en el cuello y región torácica, y puede dar idea para dilucidar el mecanismo de desarrollo de la angiogénesis. Vertebral artery is one of the arteries supplying the brain. Knowledge of the normal and variant anatomy of the vertebral artery assumes importance in clinical practice and vascular radiology. Anomalous origins of the vertebral artery from the arch of the aorta or any one of the arteries of the neck have been reported by several authors. In this report a variation of the prevertebral course of the left vertebral artery is being presented. The Vertebral artery had usual origin from the subclavian artery and had a longer prevertebral course to enter the foramen transversarium of the CII vertebra. The origin and course of the vertebral artery on the right side was normal. It is clinically important to know the origin and course of the prevertebral segment of the vertebral artery and possible variations. The present report should be of interest for clinicians with regard to vascular variations in the neck and thoracic

Redundant mechanisms are involved in suppression of default cell fates during embryonic mesenchyme and notochord induction in ascidians.

Science.gov (United States)

Kodama, Hitoshi; Miyata, Yoshimasa; Kuwajima, Mami; Izuchi, Ryoichi; Kobayashi, Ayumi; Gyoja, Fuki; Onuma, Takeshi A; Kumano, Gaku; Nishida, Hiroki

2016-08-01

During embryonic induction, the responding cells invoke an induced developmental program, whereas in the absence of an inducing signal, they assume a default uninduced cell fate. Suppression of the default fate during the inductive event is crucial for choice of the binary cell fate. In contrast to the mechanisms that promote an induced cell fate, those that suppress the default fate have been overlooked. Upon induction, intracellular signal transduction results in activation of genes encoding key transcription factors for induced tissue differentiation. It is elusive whether an induced key transcription factor has dual functions involving suppression of the default fates and promotion of the induced fate, or whether suppression of the default fate is independently regulated by other factors that are also downstream of the signaling cascade. We show that during ascidian embryonic induction, default fates were suppressed by multifold redundant mechanisms. The key transcription factor, Twist-related.a, which is required for mesenchyme differentiation, and another independent transcription factor, Lhx3, which is dispensable for mesenchyme differentiation, sequentially and redundantly suppress the default muscle fate in induced mesenchyme cells. Similarly in notochord induction, Brachyury, which is required for notochord differentiation, and other factors, Lhx3 and Mnx, are likely to suppress the default nerve cord fate redundantly. Lhx3 commonly suppresses the default fates in two kinds of induction. Mis-activation of the autonomously executed default program in induced cells is detrimental to choice of the binary cell fate. Multifold redundant mechanisms would be required for suppression of the default fate to be secure. Copyright © 2016 Elsevier Inc. All rights reserved.

Xenopus Zic3 controls notochord and organizer development through suppression of the Wnt/β-catenin signaling pathway.

Science.gov (United States)

Fujimi, Takahiko J; Hatayama, Minoru; Aruga, Jun

2012-01-15

Zic3 controls neuroectodermal differentiation and left-right patterning in Xenopus laevis embryos. Here we demonstrate that Zic3 can suppress Wnt/β-catenin signaling and control development of the notochord and Spemann's organizer. When we overexpressed Zic3 by injecting its RNA into the dorsal marginal zone of 2-cell-stage embryos, the embryos lost mesodermal dorsal midline structures and showed reduced expression of organizer markers (Siamois and Goosecoid) and a notochord marker (Xnot). Co-injection of Siamois RNA partially rescued the reduction of Xnot expression caused by Zic3 overexpression. Because the expression of Siamois in the organizer region is controlled by Wnt/β-catenin signaling, we subsequently examined the functional interaction between Zic3 and Wnt signaling. Co-injection of Xenopus Zic RNAs and β-catenin RNA with a reporter responsive to the Wnt/β-catenin cascade indicated that Zic1, Zic2, Zic3, Zic4, and Zic5 can all suppress β-catenin-mediated transcriptional activation. In addition, co-injection of Zic3 RNA inhibited the secondary axis formation caused by ventral-side injection of β-catenin RNA in Xenopus embryos. Zic3-mediated Wnt/β-catenin signal suppression required the nuclear localization of Zic3, and involved the reduction of β-catenin nuclear transport and enhancement of β-catenin degradation. Furthermore, Zic3 co-precipitated with Tcf1 (a β-catenin co-factor) and XIC (I-mfa domain containing factor required for dorsoanterior development). The findings in this report produce a novel system for fine-tuning of Wnt/β-catenin signaling. Copyright © 2011. Published by Elsevier Inc.

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.

Fox (forkhead) genes are involved in the dorso-ventral patterning of the Xenopus mesoderm.

Science.gov (United States)

El-Hodiri, H; Bhatia-Dey, N; Kenyon, K; Ault, K; Dirksen, M; Jamrich, M

2001-01-01

Fox (forkhead/winged helix) genes encode a family of transcription factors that are involved in embryonic pattern formation, regulation of tissue specific gene expression and tumorigenesis. Several of them are transcribed during Xenopus embryogenesis and are important for the patterning of ectoderm, mesoderm and endoderm. We have isolated three forkhead genes that are activated during gastrulation and play an important role in the dorso-ventral patterning of the mesoderm. XFKH1 (FoxA4b), the first vertebrate forkhead gene to be implicated in embryonic pattern formation, is expressed in the Spemann-Mangold organizer region and later in the embryonic notochord. XFKH7, the Xenopus orthologue of the murine Mfh1(Foxc2), is expressed in the presomitic mesoderm, but not in the notochord or lateral plate mesoderm. Finally, XFD-13'(FoxF1b)1 is expressed in the lateral plate mesoderm, but not in the notochord or presomitic mesoderm. Expression pattern and functional experiments indicate that these three forkhead genes are involved in the dorso-ventral patterning of the mesoderm.

Evaluation on vertebral endplate injury and adjacent intervertebral disk injury of patients with osteoporotic vertebral compression fractures by MRI and its clinical significance

International Nuclear Information System (INIS)

Shen Yu; Shen Huiliang; Fang Xiutong; Zhang Wenbo

2012-01-01

Objective: To investigate the relationship between vertebral endplate injury and adjacent intervertebral disk injury of patients with acute or sub-acute osteoporotic vertebral compression fractures (OVC-F) by MRI, and to provide basis for diagnosis of OVCF. Methods: The clinical data of a total of 66 patients with OVCF underwent vertebroplasty (76 fracture of vertebral bodies) were selected. The vertebral endplate injury and adjacent intervertebral disk injury of OVCF patients were detected by MRI. Results: There were 57 vertebral endplate injury in 76 fracture vertebral bodies (75% ). There were only 27 vertebral bodies with vertebral endplate injury in 57 fracture vertebral bodies with endplate injury (47% ), and 22 vertebral with superior and inferior vertebral endplate injury (39% ), and 8 vertebral bodies with inferior vertebral endplate injury (14% ). There were 48 vertebral bodies with intervertebral disc injury in 76 fracture vertebral bodies (63% ). There were 22 intervertebral disc injury located above the fracture of the lumbar spine in 48 vertebral bodies with intervertebral disc injury (45% ), and 19 fracture vertebral bodies with upper and lower intervertebral disc injury (40% ), and 7 intervertebral injuries located below the fracture of the lumbar spine (15% ). Conclusion: Vertebral endplate injury is frequently associated with the adjacent intervertebral disk injury. The clinical diagnosis and treatment should be emphasized in the fracture vertebral endplate damage and adjacent intervertebral disc injury. (authors)

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...

The lamprey: a jawless vertebrate model system for examining origin of the neural crest and other vertebrate traits.

Science.gov (United States)

Green, Stephen A; Bronner, Marianne E

2014-01-01

Lampreys are a group of jawless fishes that serve as an important point of comparison for studies of vertebrate evolution. Lampreys and hagfishes are agnathan fishes, the cyclostomes, which sit at a crucial phylogenetic position as the only living sister group of the jawed vertebrates. Comparisons between cyclostomes and jawed vertebrates can help identify shared derived (i.e. synapomorphic) traits that might have been inherited from ancestral early vertebrates, if unlikely to have arisen convergently by chance. One example of a uniquely vertebrate trait is the neural crest, an embryonic tissue that produces many cell types crucial to vertebrate features, such as the craniofacial skeleton, pigmentation of the skin, and much of the peripheral nervous system (Gans and Northcutt, 1983). Invertebrate chordates arguably lack unambiguous neural crest homologs, yet have cells with some similarities, making comparisons with lampreys and jawed vertebrates essential for inferring characteristics of development in early vertebrates, and how they may have evolved from nonvertebrate chordates. Here we review recent research on cyclostome neural crest development, including research on lamprey gene regulatory networks and differentiated neural crest fates. Copyright © 2014 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

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.

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

Gravity alterations are widely recognized to influence living systems. They may cause temporary or permanent effects on physiology and development at different levels, from gene expression to morphogenesis. However, the molecular mechanisms underlying these effects are often unclear, and adequate model systems to study them are required. To address this problem we developed a new experimental model of how gravity affects morphogenesis during tail regeneration in the newt Pleurodeles waltl. The effects of increased gravity on newt tail morphogenesis were first documented in two joint Russian-US NASA spaceflight experiments in the Russian Foton-M2 (2005) and Foton-M3 (2007) missions. In these experiments the shape of newt tail regenerate was found to depend on the gravity level, being dorso-ventrally symmetrical in microgravity and in neutrally-buoyant aquarium controls, versus hook-like and bent downward in 1g controls. These 1g controls were conducted in spaceflight habitats using a water-saturated PVA sponge mat. These results were reproducible in multiple spaceflight, and ground laboratory studies, both in the US at NASA ARC and in Russia at IDB RAS, and were characterized in detail using morphometry and histology approaches. The role of hypergravity in shaping morphogenesis was confirmed at NASA ARC with an experiment in the ISS Testbed 8-foot diameter centrifuge operating at 2g. Animals that experienced two-week centrifugation (the period of time used in the Foton flights) developed the same hook-like regenerates as 1g controls, and morphometric analysis revealed no significant difference between 1g and 2g groups, however both were significantly different from aquarium controls. We hypothesize that exposure to 1g or 2g during tail morphogenesis constitutes excessive loading for newts that are adapted to microgravity-like conditions in their aquatic habitat. Because Heat Shock Proteins (HSPs) are stress-induced molecules that respond to a broad variety of

Repeated vertebral augmentation for new vertebral compression fractures of postvertebral augmentation patients: a nationwide cohort study

Directory of Open Access Journals (Sweden)

Liang CL

2015-03-01

Full Text Available Cheng-Loong Liang,1 Hao-Kwan Wang,1 Fei-Kai Syu,2 Kuo-Wei Wang,1 Kang Lu,1 Po-Chou Liliang1 1Department of Neurosurgery, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan; 2Department of Pharmacy, China Medical University Hospital, Taichung City, Taiwan Purpose: Postvertebral augmentation vertebral compression fractures are common; repeated vertebral augmentation is usually performed for prompt pain relief. This study aimed to evaluate the incidence and risk factors of repeat vertebral augmentation.Methods: We performed a retrospective, nationwide, population-based longitudinal observation study, using the National Health Insurance Research Database (NHIRD of Taiwan. All patients who received vertebral augmentation for vertebral compression fractures were evaluated. The collected data included patient characteristics (demographics, comorbidities, and medication exposure and repeat vertebral augmentation. Kaplan–Meier and stratified Cox proportional hazard regressions were performed for analyses.Results: The overall incidence of repeat vertebral augmentation was 11.3% during the follow-up until 2010. Patients with the following characteristics were at greater risk for repeat vertebral augmentation: female sex (AOR=1.24; 95% confidence interval [CI]: 1.10–2.36, advanced age (AOR=1.60; 95% CI: 1.32–2.08, diabetes mellitus (AOR=4.31; 95% CI: 4.05–5.88, cerebrovascular disease (AOR=4.09; 95% CI: 3.44–5.76, dementia (AOR=1.97; 95% CI: 1.69–2.33, blindness or low vision (AOR=3.72; 95% CI: 2.32–3.95, hypertension (AOR=2.58; 95% CI: 2.35–3.47, and hyperlipidemia (AOR=2.09; 95% CI: 1.67–2.22. Patients taking calcium/ vitamin D (AOR=2.98; 95% CI: 1.83–3.93, bisphosphonates (AOR=2.11; 95% CI: 1.26–2.61, or calcitonin (AOR=4.59; 95% CI: 3.40–5.77 were less likely to undergo repeat vertebral augmentation; however, those taking steroids (AOR=7.28; 95% CI: 6.32–8.08, acetaminophen (AOR=3.54; 95% CI: 2.75–4.83, or nonsteroidal

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

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

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

Diagnosis of vertebral fractures on lateral chest X-ray: Intraobserver agreement of semi-quantitative vertebral fracture assessment

International Nuclear Information System (INIS)

Jagt-Willems, H.C. van der; Munster, B.C. van; Leeflang, M.; Beuerle, E.; Tulner, C.R.; Lems, W.F.

2014-01-01

Highlights: • (Lateral) chest X-ray's are often performed in older individuals for various reasons. • Vertebral fractures are visualized on lateral chest X-ray, but the diagnosis of vertebral fractures is until now only validated on (lateral) spine X-ray's. • This study shows that a (lateral) chest X-ray is sufficient for the diagnosis of vertebral fractures. • Older individuals with a vertebral fracture on a (lateral) chest X-ray do not need further radiography with thoracic spine X-ray or vertebral fracture assessment with DXA. - Abstract: Background: In clinical practice lateral images of the chest are performed for various reasons. As these lateral chest X rays show the vertebrae of the thoracic and thoraco-lumbar region, we wondered if these X-rays can be used for evaluation of vertebral fractures instead of separate thoracic spine X-rays. Methods: To evaluate the agreement and intraobserver reliability of the semi-quantitative method for vertebral fractures on the lateral chest X-ray (X-chest) in comparison to the lateral thoracic spine X-ray (X-Tspine), two observers scored vertebral fractures on X-Tspine and twice on X-chest, separately, blinded and in different time periods. Agreement and Cohens’ kappa were calculated for a diagnosis of any fracture on patient level and on vertebral body level. The study was done in patients visiting an outpatient geriatric day clinic, with a high prevalence of vertebral fractures. Results: 109 patients were included. The intraobserver agreement for X-chest versus X-Tspine was 95–98% for the two levels of fracturing, with a Cohen's kappa of 0.88–0.91. The intraobserver agreement and reliability of the re-test on the X-chest showed an agreement between 91 and 98% with a Cohen's kappa of 0.81–0.93. More vertebrae were visible on the X-chest, mean 10.2, SD 0.66 versus mean 9.8, SD 0.73 on the X-Tspine (p < 0.001). Conclusion: The results show good agreement and intraobserver reliability on

Diagnosis of vertebral fractures on lateral chest X-ray: Intraobserver agreement of semi-quantitative vertebral fracture assessment

Energy Technology Data Exchange (ETDEWEB)

Jagt-Willems, H.C. van der, E-mail: Hvanderjagt@spaarneziekenhuis.nl [Department of Geriatrics, Slotervaart Hospital, Amsterdam (Netherlands); Department of Internal Medicine, Spaarne Hospital, Hoofddorp (Netherlands); Munster, B.C. van [Department of Internal Medicine, Academic Medical Center, Amsterdam (Netherlands); Department of Geriatrics, Gelre Hospitals, Apeldoorn (Netherlands); Leeflang, M. [Department of Geriatrics, Gelre Hospitals, Apeldoorn (Netherlands); Beuerle, E. [Department of Radiology, Slotervaart Hospital, Amsterdam (Netherlands); Tulner, C.R. [Department of Geriatrics, Slotervaart Hospital, Amsterdam (Netherlands); Lems, W.F. [Department of Rheumatology, VU Medical Center, Amsterdam (Netherlands)

2014-12-15

Highlights: • (Lateral) chest X-ray's are often performed in older individuals for various reasons. • Vertebral fractures are visualized on lateral chest X-ray, but the diagnosis of vertebral fractures is until now only validated on (lateral) spine X-ray's. • This study shows that a (lateral) chest X-ray is sufficient for the diagnosis of vertebral fractures. • Older individuals with a vertebral fracture on a (lateral) chest X-ray do not need further radiography with thoracic spine X-ray or vertebral fracture assessment with DXA. - Abstract: Background: In clinical practice lateral images of the chest are performed for various reasons. As these lateral chest X rays show the vertebrae of the thoracic and thoraco-lumbar region, we wondered if these X-rays can be used for evaluation of vertebral fractures instead of separate thoracic spine X-rays. Methods: To evaluate the agreement and intraobserver reliability of the semi-quantitative method for vertebral fractures on the lateral chest X-ray (X-chest) in comparison to the lateral thoracic spine X-ray (X-Tspine), two observers scored vertebral fractures on X-Tspine and twice on X-chest, separately, blinded and in different time periods. Agreement and Cohens’ kappa were calculated for a diagnosis of any fracture on patient level and on vertebral body level. The study was done in patients visiting an outpatient geriatric day clinic, with a high prevalence of vertebral fractures. Results: 109 patients were included. The intraobserver agreement for X-chest versus X-Tspine was 95–98% for the two levels of fracturing, with a Cohen's kappa of 0.88–0.91. The intraobserver agreement and reliability of the re-test on the X-chest showed an agreement between 91 and 98% with a Cohen's kappa of 0.81–0.93. More vertebrae were visible on the X-chest, mean 10.2, SD 0.66 versus mean 9.8, SD 0.73 on the X-Tspine (p < 0.001). Conclusion: The results show good agreement and intraobserver reliability on

Imaging assessment of vertebral burst fracture

International Nuclear Information System (INIS)

Ding Jianlin; Liang Lihua; Wang Yujia

2006-01-01

Objective: To investigate the diagnostic value of radiography, CT and MRI in diagnosis of vertebral burst fracture. Methods: 51 patients with vertebral burst fracture were evaluated with X-ray, CT and MRI, including 3 cases in cervical vertebra, 18 cases in thoracic vertebra, and 30 cases in lumbar vertebra. The imaging features were comparatively studied. Results: Radiography showed decreased height of the vertebral body, increased antero-posterior diameter and the transverse diameter, and/or the widened interpedicle distance, the inter-spinous distance, as well as the bony fragment inserted into the vertebral canal in 28 cases(54.90%). X-ray findings similar to the compression fracture were revealed in 20 cases(39.21%). And missed diagnosis was made in 3 cases (5.88%). CT clearly demon-strated the vertebral body vertically or transversely burst crack in 49 cases (96.07%); bony fragment inserted into the vertebral canal and narrowed vertebral canal in 35 cases(68. 62% ); fracture of spinal appendix in 22 cases(43.14%). Meanwhile MRI showed abnormal signals within the spinal cord in 35 cases (68.62%),injured intervertebral disk in 29 cases(56.86% ), extradural hematoma in 12 cases(23.52% ) and torn posterior longitudinal ligament in 6 cases (11.76%). Conclusions: Radiography is the routine examination, while with limited diagnostic value in vertebral burst fracture. These patients who have nervous symptoms with simple compression fracture or unremarkable on X-ray should receive the CT or MRI examination. CT is better than MRI in demonstrating the fracture and the displaced bony fragment, while MRI is superior to CT in showing nervous injuries. CT and MRI will provide comprehensive information guiding clinical treatment of vertebral burst fracture. (authors)

Globally threatened vertebrates on islands with invasive species.

Science.gov (United States)

Spatz, Dena R; Zilliacus, Kelly M; Holmes, Nick D; Butchart, Stuart H M; Genovesi, Piero; Ceballos, Gerardo; Tershy, Bernie R; Croll, Donald A

2017-10-01

Global biodiversity loss is disproportionately rapid on islands, where invasive species are a major driver of extinctions. To inform conservation planning aimed at preventing extinctions, we identify the distribution and biogeographic patterns of highly threatened terrestrial vertebrates (classified by the International Union for Conservation of Nature) and invasive vertebrates on ~465,000 islands worldwide by conducting a comprehensive literature review and interviews with more than 500 experts. We found that 1189 highly threatened vertebrate species (319 amphibians, 282 reptiles, 296 birds, and 292 mammals) breed on 1288 islands. These taxa represent only 5% of Earth's terrestrial vertebrates and 41% of all highly threatened terrestrial vertebrates, which occur in vertebrates was available for 1030 islands (80% of islands with highly threatened vertebrates). Invasive vertebrates were absent from 24% of these islands, where biosecurity to prevent invasions is a critical management tool. On the 76% of islands where invasive vertebrates were present, management could benefit 39% of Earth's highly threatened vertebrates. Invasive mammals occurred in 97% of these islands, with Rattus sp. as the most common invasive vertebrate (78%; 609 islands). Our results provide an important baseline for identifying islands for invasive species eradication and other island conservation actions that reduce biodiversity loss.

Hormonally active phytochemicals and vertebrate evolution.

Science.gov (United States)

Lambert, Max R; Edwards, Thea M

2017-06-01

Living plants produce a diversity of chemicals that share structural and functional properties with vertebrate hormones. Wildlife species interact with these chemicals either through consumption of plant materials or aquatic exposure. Accumulating evidence shows that exposure to these hormonally active phytochemicals (HAPs) often has consequences for behavior, physiology, and fecundity. These fitness effects suggest there is potential for an evolutionary response by vertebrates to HAPs. Here, we explore the toxicological HAP-vertebrate relationship in an evolutionary framework and discuss the potential for vertebrates to adapt to or even co-opt the effects of plant-derived chemicals that influence fitness. We lay out several hypotheses about HAPs and provide a path forward to test whether plant-derived chemicals influence vertebrate reproduction and evolution. Studies of phytochemicals with direct impacts on vertebrate reproduction provide an obvious and compelling system for studying evolutionary toxicology. Furthermore, an understanding of whether animal populations evolve in response to HAPs could provide insightful context for the study of rapid evolution and how animals cope with chemical agents in the environment.

[Correlation analysis of cement leakage with volume ratio of intravertebral bone cement to vertebral body and vertebral body wall incompetence in percutaneous vertebroplasty for osteoporotic vertebral compression fractures].

Science.gov (United States)

Liang, De; Ye, Linqiang; Jiang, Xiaobing; Huang, Weiquan; Yao, Zhensong; Tang, Yongchao; Zhang, Shuncong; Jin, Daxiang

2014-11-01

To investigate the risk factors of cement leakage in percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fracture (OVCF). Between March 2011 and March 2012, 98 patients with single level OVCF were treated by PVP, and the clinical data were analyzed retrospectively. There were 13 males and 85 females, with a mean age of 77.2 years (range, 54-95 years). The mean disease duration was 43 days (range, 15-120 days), and the mean T score of bone mineral density (BMD) was -3.8 (range, -6.7- -2.5). Bilateral transpedicular approach was used in all the patients. The patients were divided into cement leakage group and no cement leakage group by occurrence of cement leakage based on postoperative CT. Single factor analysis was used to analyze the difference between 2 groups in T score of BMD, operative level, preoperative anterior compression degree of operative vertebrae, preoperative middle compression degree of operative vertebrae, preoperative sagittal Cobb angle of operative vertebrae, preoperative vertebral body wall incompetence, cement volume, and volume ratio of intravertebral bone cement to vertebral body. All relevant factors were introduced to logistic regression analysis to analyze the risk factors of cement leakage. All procedures were performed successfully. The mean operation time was 40 minutes (range, 30-50 minutes), and the mean volume ratio of intravertebral bone cement to vertebral body was 24.88% (range, 7.84%-38.99%). Back pain was alleviated significantly in all the patients postoperatively. All patients were followed up with a mean time of 8 months (range, 6-12 months). Cement leakage occurred in 49 patients. Single factor analysis showed that there were significant differences in the volume ratio of intravertebral bone cement to vertebral body and preoperative vertebral body wall incompetence between 2 groups (P 0.05). The logistic regression analysis showed that the volume ratio of intravertebral bone cement to vertebral body (P

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

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

Vertebral chondroblastoma

International Nuclear Information System (INIS)

Ilaslan, Hakan; Sundaram, Murali; Unni, Krishnan K.

2003-01-01

To determine the age distribution, gender, incidence, and imaging findings of vertebral chondroblastoma, and to compare our series with findings from case reports in the world literature.Design and patients Case records and imaging findings of nine histologically documented vertebral chondroblastomas were retrospectively reviewed for patient age, gender, vertebral column location and level, morphology, matrix, edema, soft tissue mass, spinal canal invasion, and metastases. Our findings were compared with a total of nine patients identified from previous publications in the world literature. The histologic findings in our cases was re-reviewed for diagnosis and specifically for features of calcification and secondary aneurysmal bone cyst (ABC). Clinical follow-up was requested from referring institutions. Nine of 856 chondroblastomas arose in vertebrae (incidence 1.4%; thoracic 5, lumbar 1, cervical 2, sacral 1). There were six males and three females ranging in age from 5 to 41 years (mean 28 years). Satisfactory imaging from seven patients revealed the tumor to arise from the posterior elements in four and the body in three. All tumors were expansive, six of seven were aggressive, and the spinal canal was significantly narrowed by bone or soft tissue mass in six. In one patient canal invasion was minimal. Calcification was pronounced in two and subtle in four. The sole nonaggressive-appearing tumor was heavily mineralized. Bony edema and secondary ABC were not seen on MR imaging. None of the cases had microscopic features of significant secondary ABC. Calcification, and specifically ''chicken wire'' calcification, was identified in two patients. Pulmonary metastases occurred in none. Vertebral chondroblastoma is a rare neoplasm that presents later in life than its appendicular counterpart. On imaging it is aggressive in appearance with bone destruction, soft tissue mass, and spinal canal invasion. The lesions contain variable amounts of mineral. Secondary

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...

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

Vertebral Augmentation Involving Vertebroplasty or Kyphoplasty for Cancer-Related Vertebral Compression Fractures: An Economic Analysis.

Science.gov (United States)

2016-01-01

Untreated vertebral compression fractures can have serious clinical consequences and impose a considerable impact on patients' quality of life and on caregivers. Since non-surgical management of these fractures has limited effectiveness, vertebral augmentation procedures are gaining acceptance in clinical practice for pain control and fracture stabilization. The objective of this analysis was to determine the cost-effectiveness and budgetary impact of kyphoplasty or vertebroplasty compared with non-surgical management for the treatment of vertebral compression fractures in patients with cancer. We performed a systematic review of health economic studies to identify relevant studies that compare the cost-effectiveness of kyphoplasty or vertebroplasty with non-surgical management for the treatment of vertebral compression fractures in adults with cancer. We also performed a primary cost-effectiveness analysis to assess the clinical benefits and costs of kyphoplasty or vertebroplasty compared with non-surgical management in the same population. We developed a Markov model to forecast benefits and harms of treatments, and corresponding quality-adjusted life years and costs. Clinical data and utility data were derived from published sources, while costing data were derived using Ontario administrative sources. We performed sensitivity analyses to examine the robustness of the results. In addition, a 1-year budget impact analysis was performed using data from Ontario administrative sources. Two scenarios were explored: (a) an increase in the total number of vertebral augmentation procedures performed among patients with cancer in Ontario, maintaining the current proportion of kyphoplasty versus vertebroplasty; and (b) no increase in the total number of vertebral augmentation procedures performed among patients with cancer in Ontario but an increase in the proportion of kyphoplasties versus vertebroplasties. The base case considered each of kyphoplasty and vertebroplasty

Imaging of vertebral fracture in osteoporosis

International Nuclear Information System (INIS)

Skowronska-Jozwiak, E.; Lewinski, A.; Bieganski, T.

2008-01-01

Vertebral collapses are the most frequent fractures in osteoporosis. They are often overlooked, although their presence is a strong risk factor for development of new fractures. Lateral radiographs of the spine are the accepted standard for assessment of fractures. Qualitative (visual), semiquantitative and quantitative (morphometric) techniques are useful in determining the compressive deformities of vertebral bodies. In the present paper, the advantages and the disadvantages of these methods are discussed. The improvement of scan quality allows to use DXA technique to diagnose the fractures, in both - the visual and the morphometric way. The vertebral morphologic assessment also seems to be an important diagnostic tool in pediatric osteoporosis. Application of multidetector CT and especially MR in vertebral imaging of osteoporosis, improves the sensitivity of fracture detection and enables the differentiation of benign from malignant vertebral body collapses. (author)

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...

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.

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.

CIRSE Guidelines on Percutaneous Vertebral Augmentation

Energy Technology Data Exchange (ETDEWEB)

Tsoumakidou, Georgia, E-mail: gtsoumakidou@yahoo.com; Too, Chow Wei, E-mail: spyder55@gmail.com; Koch, Guillaume, E-mail: guillaume.koch@gmail.com; Caudrelier, Jean, E-mail: jean.caudrelier@chru-strasbourg.fr; Cazzato, Roberto Luigi, E-mail: gigicazzato@hotmail.it; Garnon, Julien, E-mail: juliengarnon@gmail.com; Gangi, Afshin, E-mail: gangi@unistra.fr [Strasbourg University Hospital, Interventional Radiology Department (France)

2017-03-15

Vertebral compression fracture (VCF) is an important cause of severe debilitating back pain, adversely affecting quality of life, physical function, psychosocial performance, mental health and survival. Different vertebral augmentation procedures (VAPs) are used in order to consolidate the VCFs, relief pain,and whenever posible achieve vertebral body height restoration. In the present review we give the indications, contraindications, safety profile and outcomes of the existing percutaneous VAPs.

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.

Vertebrate Left-Right Asymmetry: What Can Nodal Cascade Gene Expression Patterns Tell Us?

Science.gov (United States)

Schweickert, Axel; Ott, Tim; Kurz, Sabrina; Tingler, Melanie; Maerker, Markus; Fuhl, Franziska; Blum, Martin

2017-12-29

Laterality of inner organs is a wide-spread characteristic of vertebrates and beyond. It is ultimately controlled by the left-asymmetric activation of the Nodal signaling cascade in the lateral plate mesoderm of the neurula stage embryo, which results from a cilia-driven leftward flow of extracellular fluids at the left-right organizer. This scenario is widely accepted for laterality determination in wildtype specimens. Deviations from this norm come in different flavors. At the level of organ morphogenesis, laterality may be inverted (situs inversus) or non-concordant with respect to the main body axis (situs ambiguus or heterotaxia). At the level of Nodal cascade gene activation, expression may be inverted, bilaterally induced, or absent. In a given genetic situation, patterns may be randomized or predominantly lacking laterality (absence or bilateral activation). We propose that the distributions of patterns observed may be indicative of the underlying molecular defects, with randomizations being primarily caused by defects in the flow-generating ciliary set-up, and symmetrical patterns being the result of impaired flow sensing, on the left, the right, or both sides. This prediction, the reasoning of which is detailed in this review, pinpoints functions of genes whose role in laterality determination have remained obscure.

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.

Light adaptation and the evolution of vertebrate photoreceptors.

Science.gov (United States)

Morshedian, Ala; Fain, Gordon L

2017-07-15

Lamprey are cyclostomes, a group of vertebrates that diverged from lines leading to jawed vertebrates (including mammals) in the late Cambrian, 500 million years ago. It may therefore be possible to infer properties of photoreceptors in early vertebrate progenitors by comparing lamprey to other vertebrates. We show that lamprey rods and cones respond to light much like rods and cones in amphibians and mammals. They operate over a similar range of light intensities and adapt to backgrounds and bleaches nearly identically. These correspondences are pervasive and detailed; they argue for the presence of rods and cones very early in the evolution of vertebrates with properties much like those of rods and cones in existing vertebrate species. The earliest vertebrates were agnathans - fish-like organisms without jaws, which first appeared near the end of the Cambrian radiation. One group of agnathans became cyclostomes, which include lamprey and hagfish. Other agnathans gave rise to jawed vertebrates or gnathostomes, the group including all other existing vertebrate species. Because cyclostomes diverged from other vertebrates 500 million years ago, it may be possible to infer some of the properties of the retina of early vertebrate progenitors by comparing lamprey to other vertebrates. We have previously shown that rods and cones in lamprey respond to light much like photoreceptors in other vertebrates and have a similar sensitivity. We now show that these affinities are even closer. Both rods and cones adapt to background light and to bleaches in a manner almost identical to other vertebrate photoreceptors. The operating range in darkness is nearly the same in lamprey and in amphibian or mammalian rods and cones; moreover background light shifts response-intensity curves downward and to the right over a similar range of ambient intensities. Rods show increment saturation at about the same intensity as mammalian rods, and cones never saturate. Bleaches decrease

An invertebrate stomach's view on vertebrate ecology

DEFF Research Database (Denmark)

Calvignac-Spencer, Sébastien; Leendertz, Fabian H.; Gilbert, Tom

2013-01-01

Recent studies suggest that vertebrate genetic material ingested by invertebrates (iDNA) can be used to investigate vertebrate ecology. Given the ubiquity of invertebrates that feed on vertebrates across the globe, iDNA might qualify as a very powerful tool for 21st century population...

Vertebral architecture in the earliest stem tetrapods.

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Pierce, Stephanie E; Ahlberg, Per E; Hutchinson, John R; Molnar, Julia L; Sanchez, Sophie; Tafforeau, Paul; Clack, Jennifer A

2013-02-14

The construction of the vertebral column has been used as a key anatomical character in defining and diagnosing early tetrapod groups. Rhachitomous vertebrae--in which there is a dorsally placed neural arch and spine, an anteroventrally placed intercentrum and paired, posterodorsally placed pleurocentra--have long been considered the ancestral morphology for tetrapods. Nonetheless, very little is known about vertebral anatomy in the earliest stem tetrapods, because most specimens remain trapped in surrounding matrix, obscuring important anatomical features. Here we describe the three-dimensional vertebral architecture of the Late Devonian stem tetrapod Ichthyostega using propagation phase-contrast X-ray synchrotron microtomography. Our scans reveal a diverse array of new morphological, and associated developmental and functional, characteristics, including a possible posterior-to-anterior vertebral ossification sequence and the first evolutionary appearance of ossified sternal elements. One of the most intriguing features relates to the positional relationships between the vertebral elements, with the pleurocentra being unexpectedly sutured or fused to the intercentra that directly succeed them, indicating a 'reverse' rhachitomous design. Comparison of Ichthyostega with two other stem tetrapods, Acanthostega and Pederpes, shows that reverse rhachitomous vertebrae may be the ancestral condition for limbed vertebrates. This study fundamentally revises our current understanding of vertebral column evolution in the earliest tetrapods and raises questions about the presumed vertebral architecture of tetrapodomorph fish and later, more crownward, tetrapods.

Vertebrate pressure-gradient receivers

DEFF Research Database (Denmark)

Christensen-Dalsgaard, Jakob

2011-01-01

The eardrums of all terrestrial vertebrates (tetrapods) are connected through Eustachian tubes or interaural canals. In some of the animals, these connections create pressure-gradient directionality, an enhanced directionality by interaction of sound arriving at both sides of the eardrum and stro......The eardrums of all terrestrial vertebrates (tetrapods) are connected through Eustachian tubes or interaural canals. In some of the animals, these connections create pressure-gradient directionality, an enhanced directionality by interaction of sound arriving at both sides of the eardrum....... Recent vertebrates form a continuum from perfect interaural transmission (0 dB in a certain frequency band) and pronounced eardrum directionality (30-40 dB) in the lizards, over somewhat attenuated transmission and limited directionality in birds and frogs, to the strongly attenuated interaural...

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

Head segmentation in vertebrates

OpenAIRE

Kuratani, Shigeru; Schilling, Thomas

2008-01-01

Classic theories of vertebrate head segmentation clearly exemplify the idealistic nature of comparative embryology prior to the 20th century. Comparative embryology aimed at recognizing the basic, primary structure that is shared by all vertebrates, either as an archetype or an ancestral developmental pattern. Modern evolutionary developmental (Evo-Devo) studies are also based on comparison, and therefore have a tendency to reduce complex embryonic anatomy into overly simplified patterns. Her...

Extensive molecular differences between anterior- and posterior-half-sclerotomes underlie somite polarity and spinal nerve segmentation

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Keynes Roger J

2009-05-01

Full Text Available Abstract Background The polarization of somite-derived sclerotomes into anterior and posterior halves underlies vertebral morphogenesis and spinal nerve segmentation. To characterize the full extent of molecular differences that underlie this polarity, we have undertaken a systematic comparison of gene expression between the two sclerotome halves in the mouse embryo. Results Several hundred genes are differentially-expressed between the two sclerotome halves, showing that a marked degree of molecular heterogeneity underpins the development of somite polarity. Conclusion We have identified a set of genes that warrant further investigation as regulators of somite polarity and vertebral morphogenesis, as well as repellents of spinal axon growth. Moreover the results indicate that, unlike the posterior half-sclerotome, the central region of the anterior-half-sclerotome does not contribute bone and cartilage to the vertebral column, being associated instead with the development of the segmented spinal nerves.

Transgenic Expression of Constitutively Active RAC1 Disrupts Mouse Rod Morphogenesis

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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

Prevalent Vertebral Fractures in Black Women and White Women

OpenAIRE

Cauley, Jane A; Palermo, Lisa; Vogt, Molly; Ensrud, Kristine E; Ewing, Susan; Hochberg, Marc; Nevitt, Michael C; Black, Dennis M

2008-01-01

Vertebral fractures are the most common osteoporotic fracture. Hip and clinical fractures are less common in black women, but there is little information on vertebral fractures. We studied 7860 white and 472 black women ≥65 yr of age enrolled in the Study of Osteoporotic Fractures. Prevalent vertebral fractures were identified from lateral spine radiographs using vertebral morphometry and defined if any vertebral height ratio was >3 SD below race-specific means for each vertebral level. Infor...

Evolution of circadian organization in vertebrates

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M. Menaker

1997-03-01

Full Text Available Circadian organization means the way in which the entire circadian system above the cellular level is put together physically and the principles and rules that determine the interactions among its component parts which produce overt rhythms of physiology and behavior. Understanding this organization and its evolution is of practical importance as well as of basic interest. The first major problem that we face is the difficulty of making sense of the apparently great diversity that we observe in circadian organization of diverse vertebrates. Some of this diversity falls neatly into place along phylogenetic lines leading to firm generalizations: i in all vertebrates there is a "circadian axis" consisting of the retinas, the pineal gland and the suprachiasmatic nucleus (SCN, ii in many non-mammalian vertebrates of all classes (but not in any mammals the pineal gland is both a photoreceptor and a circadian oscillator, and iii in all non-mammalian vertebrates (but not in any mammals there are extraretinal (and extrapineal circadian photoreceptors. An interesting explanation of some of these facts, especially the differences between mammals and other vertebrates, can be constructed on the assumption that early in their evolution mammals passed through a "nocturnal bottleneck". On the other hand, a good deal of the diversity among the circadian systems of vertebrates does not fall neatly into place along phylogenetic lines. In the present review we will consider how we might better understand such "phylogenetically incoherent" diversity and what sorts of new information may help to further our understanding of the evolution of circadian organization in vertebrates

Vertebral chondroblastoma

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Ilaslan, Hakan; Sundaram, Murali [Department of Radiology, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905 (United States); Unni, Krishnan K. [Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905 (United States)

2003-02-01

To determine the age distribution, gender, incidence, and imaging findings of vertebral chondroblastoma, and to compare our series with findings from case reports in the world literature.Design and patients Case records and imaging findings of nine histologically documented vertebral chondroblastomas were retrospectively reviewed for patient age, gender, vertebral column location and level, morphology, matrix, edema, soft tissue mass, spinal canal invasion, and metastases. Our findings were compared with a total of nine patients identified from previous publications in the world literature. The histologic findings in our cases was re-reviewed for diagnosis and specifically for features of calcification and secondary aneurysmal bone cyst (ABC). Clinical follow-up was requested from referring institutions. Nine of 856 chondroblastomas arose in vertebrae (incidence 1.4%; thoracic 5, lumbar 1, cervical 2, sacral 1). There were six males and three females ranging in age from 5 to 41 years (mean 28 years). Satisfactory imaging from seven patients revealed the tumor to arise from the posterior elements in four and the body in three. All tumors were expansive, six of seven were aggressive, and the spinal canal was significantly narrowed by bone or soft tissue mass in six. In one patient canal invasion was minimal. Calcification was pronounced in two and subtle in four. The sole nonaggressive-appearing tumor was heavily mineralized. Bony edema and secondary ABC were not seen on MR imaging. None of the cases had microscopic features of significant secondary ABC. Calcification, and specifically ''chicken wire'' calcification, was identified in two patients. Pulmonary metastases occurred in none. Vertebral chondroblastoma is a rare neoplasm that presents later in life than its appendicular counterpart. On imaging it is aggressive in appearance with bone destruction, soft tissue mass, and spinal canal invasion. The lesions contain variable amounts of mineral

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.

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

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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.

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

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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.

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.

Factors for vertebral artery injury accompanied by cervical trauma

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Murata, Masaaki; Shingu, Hikosuke; Kimura, Isao; Nasu, Yoshiro; Shiotani, Akihide [San-in Rosai Hospital, Yonago, Tottori (Japan). Spine and Low Back Pain Center

2001-09-01

Injury of the vertebral artery with cerebellar and brain stem infarction is a complication of cervical vertebral trauma. However, the pathogenesis and etiological factors remain to be clarified. In this study, we investigated patients with cervical vertebral and cord injury. This study included 51 patients with cervical vertebral and cord injury who were treated in our department. In these patients, plain X-ray, CT, MRI, and MRA findings were examined. The incidence of vertebral arterial injury was 33.3% (17 of 51 patients with cervical vertebral trauma). In 11 of the 17 patients, dislocation fracture was noted, comprising a markedly high percentage (64.7%). Particularly, vertebral arterial injury was commonly observed in patients with a large dislocation distance and severe paralysis. Cerebellar and brain stem infarction related to vertebral arterial injury was observed in 5 of the 17 patients (29.4%). No infarction developed in patients 50 years old or younger. Infarction was detected in relatively elderly patients. Vertebral arterial injury and cerebellar/brain stem infarction related to cervical vertebral trauma were frequently observed in patients with high energy injury. However, these disorders commonly occurred in elderly patients. Therefore, age-related factors such as arteriosclerosis may also be closely involved. In the acute stage, the state of the vertebral artery should be evaluated by MRA and MRI. Among patients with vertebral arterial injury, caution is needed during follow-up those with risk factors such as high energy injury and advanced age. (author)

Factors for vertebral artery injury accompanied by cervical trauma

International Nuclear Information System (INIS)

Murata, Masaaki; Shingu, Hikosuke; Kimura, Isao; Nasu, Yoshiro; Shiotani, Akihide

2001-01-01

Injury of the vertebral artery with cerebellar and brain stem infarction is a complication of cervical vertebral trauma. However, the pathogenesis and etiological factors remain to be clarified. In this study, we investigated patients with cervical vertebral and cord injury. This study included 51 patients with cervical vertebral and cord injury who were treated in our department. In these patients, plain X-ray, CT, MRI, and MRA findings were examined. The incidence of vertebral arterial injury was 33.3% (17 of 51 patients with cervical vertebral trauma). In 11 of the 17 patients, dislocation fracture was noted, comprising a markedly high percentage (64.7%). Particularly, vertebral arterial injury was commonly observed in patients with a large dislocation distance and severe paralysis. Cerebellar and brain stem infarction related to vertebral arterial injury was observed in 5 of the 17 patients (29.4%). No infarction developed in patients 50 years old or younger. Infarction was detected in relatively elderly patients. Vertebral arterial injury and cerebellar/brain stem infarction related to cervical vertebral trauma were frequently observed in patients with high energy injury. However, these disorders commonly occurred in elderly patients. Therefore, age-related factors such as arteriosclerosis may also be closely involved. In the acute stage, the state of the vertebral artery should be evaluated by MRA and MRI. Among patients with vertebral arterial injury, caution is needed during follow-up those with risk factors such as high energy injury and advanced age. (author)

Proposed Diagnostic Criteria, Classification Schema, and Review of Literature of Notochord-Derived Ecchordosis Physaliphora

Science.gov (United States)

Lagman, Carlito; Sarmiento, J. Manuel; Turtz, Alan R; Chitale, Rohan V

2016-01-01

Ecchordosis physaliphora (EP) is a benign notochordal remnant derived from ectopic nests found along the craniospinal axis. It typically presents asymptomatically and is diagnosed using classic radiologic features, particularly location, T1-hypointensity, T2-hyperintensity, and lack of enhancement following gadolinium (Gd) contrast administration. Distinguishing EP from its malignant counterpart, chordoma, is of paramount importance, given the aggressive nature of the latter. Advances in imaging and immunohistochemistry have aided in diagnosis to an extent but, to our knowledge, identification of the genetic fingerprint of EP has yet to take place. Further cytological analysis of these lesions in search of a genetic link is warranted. We propose here a set of diagnostic criteria based on features consistently cited in the literature. In this literature review, 23 case reports were identified and collated into a summary of symptomatic cases of ecchordosis physaliphora. An illustrative case report of two patients was also included.  PMID:27158576

Initial non-weight-bearing therapy is important for preventing vertebral body collapse in elderly patients with clinical vertebral fractures

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Kishikawa Y

2012-04-01

Full Text Available Yoichi KishikawaKishikawa Orthopaedic Clinic, Saga City, Saga, JapanPurpose: The aim of the present conventional observational study was to compare the clinical outcomes of initial non-weight-bearing therapy and conventional relative rest therapy among elderly patients with clinical vertebral fractures.Methods: In total, 196 consecutive patients with clinical vertebral fractures (mean age: 78 years who were hospitalized for treatment between January 1999 and March 2007 were analyzed. Initial non-weight-bearing therapy consisted of complete bed rest allowing rolling on the bed without any weight-bearing to the spine for 2 weeks, followed by rehabilitation wearing a soft brace. The indications for initial non-weight-bearing therapy were vertebral fracture involving the posterior portion of the vertebral body at the thoraco-lumbar spine, mild neurological deficit, instability of the fracture site, severe pain, multiple vertebral fractures arising from trauma, malalignment at the fracture site, and mild spinal canal stenosis caused by the fracture. Patients who met the indication criteria were treated with initial non-weight-bearing therapy (n = 103, while the other patients were treated with conventional relative rest (n = 93. All the patients were uniformly treated with intramuscular elcatonin to relieve pain. The primary endpoint was progression of the vertebral fracture. The secondary endpoints included bony union and subjective back pain. The follow-up period was 12 weeks.Results: Compared with the conventional relative rest group, the collapse rate of the anterior and posterior portions of the vertebral body was significantly smaller in the initial non-weight-bearing group. The bony union rate was 100% in the initial non-weight-bearing group and 97% in the conventional relative rest group. The number of patients who experienced back pain was significantly lower in the initial non-weight-bearing group than in the conventional relative rest

Vertebral morphometry by dual-energy X-ray absorptiometry

International Nuclear Information System (INIS)

Boyanov, M.

2002-01-01

Vertebral fractures are a key feature of overt osteoporosis. Different X-ray morphometric techniques have been developed for quantification of changes in vertebral body shape. In recent years, a new method was implemented based on dual-energy X-ray absorptiometry. Morphometric X-ray absorptiometry, MXA, is a source of lower radiation and there is no image distortion. Several aspects of its application are under heavy discussion: image quality, accuracy and precision, reference databases, age changes in vertebral shape. The differential diagnosis of vertebral fracture/deformity is difficult. MXA has prove its value in large epidemiological studies on prevalence of vertebral deformities, as well in assessing the effects of different diseases and medications on vertebral body architecture. MXA is a promising method for future research and clinical work. (author)

Trunk muscle activity is modified in osteoporotic vertebral fracture and thoracic kyphosis with potential consequences for vertebral health.

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Alison M Greig

Full Text Available This study explored inter-relationships between vertebral fracture, thoracic kyphosis and trunk muscle control in elderly people with osteoporosis. Osteoporotic vertebral fractures are associated with increased risk of further vertebral fractures; but underlying mechanisms remain unclear. Several factors may explain this association, including changes in postural alignment (thoracic kyphosis and altered trunk muscle contraction patterns. Both factors may increase risk of further fracture because of increased vertebral loading and impaired balance, which may increase falls risk. This study compared postural adjustments in 24 individuals with osteoporosis with and without vertebral fracture and with varying degrees of thoracic kyphosis. Trunk muscle electromyographic activity (EMG associated with voluntary arm movements was recorded and compared between individuals with and without vertebral fracture, and between those with low and high thoracic kyphosis. Overall, elderly participants in the study demonstrated co-contraction of the trunk flexor and extensor muscles during forwards arm movements, but those with vertebral fractures demonstrated a more pronounced co-contraction than those without fracture. Individuals with high thoracic kyphosis demonstrated more pronounced alternating flexor and extensor EMG bursts than those with less kyphosis. Co-contraction of trunk flexor and extensor muscles in older individuals contrasts the alternating bursts of antagonist muscle activity in previous studies of young individuals. This may have several consequences, including altered balance efficacy and the potential for increased compressive loads through the spine. Both of these outcomes may have consequences in a population with fragile vertebrae who are susceptible to fracture.

Plant morphogenesis, auxin, and the signal-trafficking network incompleteness theorem

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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

Hemifacial spasm; The value of vertebral angiography

International Nuclear Information System (INIS)

Yang, Hak Seok; Kim, Myung Soon; Han, Yong Pyo

1992-01-01

In order to evaluate the value of vertebral angiography in assesment of hemifacial spasm, We reviewed retrospectively the vertebral angiography of 28 patients (30 cases) with surgically proved hemifacial spasm but normal CT scans of posterior fossa. There were 9 males and 19 females. Angiography revealed vascular focus of hemifacial spasm located at anterior inferior cerebellar artery , posterior inferior cerebellar artery, and vertebral artery in 19, 9, and 2 cases respectively. Right side was involved in 20 cases. All involved vessels were elongated, tortuous, and dilated. In conclusion, vertebral angiography was valuable in evaluating hemifacial spasm of vascular origin in the posterior fossa

MR imaging of tuberculous vertebral osteomyelitis: pictorial review

Energy Technology Data Exchange (ETDEWEB)

Gouliamos, A.D.; Kehagias, D.T.; Lahanis, S.; Moulopoulou, E.S.; Kalovidouris, A.A.; Trakadas, S.J.; Vlahos, L.j. [Dept. of Radiology, University of Athens (Greece); Athanassopoulou, A.A. [Dept. of Radiology, Asklipiion Hospital, Athens (Greece)

2001-04-01

Vertebral osteomyelitis is one of the most common manifestations of tuberculosis. Magnetic resonance imaging is considered the main imaging modality for the diagnosis, the demonstration of the extent of the disease, and follow-up studies. Vertebral destruction involving two consecutive levels with sparing of the intervertebral disc, disc herniation into the vertebral body, epidural involvement, and paraspinal abscess are the most common MRI findings suggestive of tuberculous vertebral osteomyelitis. (orig.)

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.

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...

Metamerism in cephalochordates and the problem of the vertebrate head.

Science.gov (United States)

Onai, Takayuki; Adachi, Noritaka; Kuratani, Shigeru

2017-01-01

The vertebrate head characteristically exhibits a complex pattern with sense organs, brain, paired eyes and jaw muscles, and the brain case is not found in other chordates. How the extant vertebrate head has evolved remains enigmatic. Historically, there have been two conflicting views on the origin of the vertebrate head, segmental and non-segmental views. According to the segmentalists, the vertebrate head is organized as a metameric structure composed of segments equivalent to those in the trunk; a metamere in the vertebrate head was assumed to consist of a somite, a branchial arch and a set of cranial nerves, considering that the head evolved from rostral segments of amphioxus-like ancestral vertebrates. Non-segmentalists, however, considered that the vertebrate head was not segmental. In that case, the ancestral state of the vertebrate head may be non-segmented, and rostral segments in amphioxus might have been secondarily gained, or extant vertebrates might have evolved through radical modifications of amphioxus-like ancestral vertebrate head. Comparative studies of mesodermal development in amphioxus and vertebrate gastrula embryos have revealed that mesodermal gene expressions become segregated into two domains anteroposteriorly to specify the head mesoderm and trunk mesoderm only in vertebrates; in this segregation, key genes such as delta and hairy, involved in segment formation, are expressed in the trunk mesoderm, but not in the head mesoderm, strongly suggesting that the head mesoderm of extant vertebrates is not segmented. Taken together, the above finding possibly adds a new insight into the origin of the vertebrate head; the vertebrate head mesoderm would have evolved through an anteroposterior polarization of the paraxial mesoderm if the ancestral vertebrate had been amphioxus-like.

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.

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.

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.

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...

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.

Variations in the formation of the human caudal spinal cord.

Science.gov (United States)

Saraga-Babić, M; Sapunar, D; Wartiovaara, J

1995-01-01

Collection of 15 human embryos between 4-8 developmental weeks was used to histologically investigate variations in the development of the caudal part of the spinal cord and the neighboring axial organs (notochord and vertebral column). In the 4-week embryo, two types of neurulation were parallelly observed along the anteroposterior body axis: primary in the areas cranial to the neuroporus caudalis and secondary in the more caudal tail regions. In the 5-week embryos, both parts of the neural tube fused, forming only one continuous lumen in the developing spinal cord. In the three examined embryos we found anomalous pattern of spinal cord formation. Caudal parts of these spinal cords displayed division of their central canal into two or three separate lumina, each surrounded by neuroepithelial layer. In the caudal area of the spinal cord, derived by secondary neurulation, formation of separate lumina was neither connected to any anomalous notochord or vertebral column formation, nor the appearance of any major axial disturbances. We suggest that development of the caudal part of the spinal cord differs from its cranial region not only in the type of neurulation, but also in the destiny of its derivatives and possible modes of abnormality formation.

Lumbar Vertebral Canal Diameters in Adult Ugandan Skeletons ...

African Journals Online (AJOL)

Background: Normal values of lumbar vertebral canal diameters are useful in facilitating diagnosis of lumbar vertebral canal stenosis. Various studies have established variation on values between different populations, gender, age, and ethnic groups. Objectives: To determine the lumbar vertebral canal diameters in adult ...

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

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.

The shape of the human lumbar vertebral canal

OpenAIRE

Zarzur,Edmundo

1996-01-01

Literature on the anatomy of the human vertebral column characterizes the shape of the lumbar vertebral canal as triangular. The purpose of the present study was to determine the precise shape of the lumbar vertebral canal. Ten lumbar vertebral columns of adult male cadavers were dissected. Two transverse sections were performed in the third lumbar vertebra. One section was performed at the level of the lower border of the ligamenta flava, and the other section was performed at the level of t...

A Case of Duplicated Right Vertebral Artery.

Science.gov (United States)

Motomura, Mayuko; Watanabe, Koichi; Tabira, Yoko; Iwanaga, Joe; Matsuuchi, Wakako; Yoshida, Daichi; Saga, Tsuyoshi; Yamaki, Koh-Ichi

2018-04-27

We encountered a case of duplicated right vertebral artery during an anatomical dissection course for medical students in 2015. Two vertebral arteries were found in the right neck of a 91-year-old female cadaver. The proximal leg of the arteries arose from the area between the right subclavian artery and the right common carotid artery that diverged from the brachiocephalic artery. The distal leg arose from the right subclavian artery as expected. The proximal leg entered the transverse foramen of the fourth cervical vertebra and the distal leg entered the transverse foramen of the sixth cervical vertebra. The two right vertebral arteries joined to form one artery just after the origin of the right vertebral artery of the brachiocephalic artery entered the transverse foramen of the fourth cervical vertebra. This artery then traveled up in the transverse foramina and became the basilar artery, joining with the left vertebral artery. We discuss the embryological origin of this case and review previously reported cases.

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.

Innate immunity in vertebrates: an overview.

Science.gov (United States)

Riera Romo, Mario; Pérez-Martínez, Dayana; Castillo Ferrer, Camila

2016-06-01

Innate immunity is a semi-specific and widely distributed form of immunity, which represents the first line of defence against pathogens. This type of immunity is critical to maintain homeostasis and prevent microbe invasion, eliminating a great variety of pathogens and contributing with the activation of the adaptive immune response. The components of innate immunity include physical and chemical barriers, humoral and cell-mediated components, which are present in all jawed vertebrates. The understanding of innate defence mechanisms in non-mammalian vertebrates is the key to comprehend the general picture of vertebrate innate immunity and its evolutionary history. This is also essential for the identification of new molecules with applications in immunopharmacology and immunotherapy. In this review, we describe and discuss the main elements of vertebrate innate immunity, presenting core findings in this field and identifying areas that need further investigation. © 2016 John Wiley & Sons Ltd.

Assisted techniques for vertebral cementoplasty: Why should we do it?

Energy Technology Data Exchange (ETDEWEB)

Muto, M., E-mail: mutomar@tiscali.it [Department of Diagnostic Imaging, Section of Neuroradiology—“A. Cardarelli” Hospital, Naples (Italy); Marcia, S. [Section of Radiology—Santissima Trinità Hospital, Cagliari (Italy); Guarnieri, G. [Department of Diagnostic Imaging, Section of Neuroradiology—“A. Cardarelli” Hospital, Naples (Italy); Pereira, V. [Unit of Interventional Neuroradiology–HUG, Geneva (Switzerland)

2015-05-15

Assisted techniques (AT) for vertebral cementoplasty include multiple mini-invasive percutaneous systems in which vertebral augmentation is obtained through mechanical devices with the aim to reach the best vertebral height restoration. As an evolution of the vertebroplasty, the rationale of the AT-treatment is to combine the analgesic and stability effect of cement injection with the restoration of a physiological height for the collapsed vertebral body. Reduction of the vertebral body kyphotic deformity, considering the target of normal spine biomechanics, could improve all systemic potential complications evident in patient with vertebral compression fracture (VCF). Main indications for AT are related to fractures in fragile vertebral osseous matrix and non-osteoporotic vertebral lesions due to spine metastasis or trauma. Many companies developed different systems for AT having the same target but different working cannula, different vertebral height restoration system and costs. Aim of this review is to discuss about vertebral cementoplasty procedures and techniques, considering patient inclusion and exclusion criteria as well as all related minor and/or major interventional complications.

Assisted techniques for vertebral cementoplasty: Why should we do it?

International Nuclear Information System (INIS)

Muto, M.; Marcia, S.; Guarnieri, G.; Pereira, V.

2015-01-01

Assisted techniques (AT) for vertebral cementoplasty include multiple mini-invasive percutaneous systems in which vertebral augmentation is obtained through mechanical devices with the aim to reach the best vertebral height restoration. As an evolution of the vertebroplasty, the rationale of the AT-treatment is to combine the analgesic and stability effect of cement injection with the restoration of a physiological height for the collapsed vertebral body. Reduction of the vertebral body kyphotic deformity, considering the target of normal spine biomechanics, could improve all systemic potential complications evident in patient with vertebral compression fracture (VCF). Main indications for AT are related to fractures in fragile vertebral osseous matrix and non-osteoporotic vertebral lesions due to spine metastasis or trauma. Many companies developed different systems for AT having the same target but different working cannula, different vertebral height restoration system and costs. Aim of this review is to discuss about vertebral cementoplasty procedures and techniques, considering patient inclusion and exclusion criteria as well as all related minor and/or major interventional complications

Endplates Changes Related to Age and Vertebral Segment

Directory of Open Access Journals (Sweden)

Carlos Fernando P. S. Herrero

2014-01-01

Full Text Available Endplate separations are defined as the presence of a space between the hyaline cartilage and the cortical bone of the adjacent vertebral body. This study evaluates endplate separations from the vertebral body and intervertebral discs and verifies if endplate separation is related to age and the spinal level. Groups were formed based on age (20–40 and 41–85 years old and the vertebral segment (T7-T8 and L4-L5 segments. Histological analysis included assessment of the length of the vertebral endplates, the number and dimensions of the separations, and orientation of the collagen fibers, in the mid-sagittal slice. Two indexes were created: the separation index (number of separations/vertebral length and separation extension index (sum of all separations/vertebral length. The results of the study demonstrated a direct relationship between the density of separations in the endplate and two variables: age and spinal level.

Duplication of the Left Vertebral Artery Origin: A Case Report

Energy Technology Data Exchange (ETDEWEB)

Shin, Sang Wook; Park, Dong Woo; Park, Choong Ki; Lee, Young Jun [Dept. of Radiology, College of Medicine, Hanyang University, Hanyang University Guri Hospital, Guri (Korea, Republic of)

2013-01-15

Duplication of vertebral arteries is a very rare but clinically important condition. A duplicated vertebral artery origin can influence hemodynamics, pathogenesis of vascular lesions and treatment options. In cases of vertebral artery duplication, the vertebral arteries generally enter the transverse foramen higher up than normal. Awareness of these vertebral artery variants before procedures, such as neurointervention or surgery, may be beneficial. Here, we describe a case of a 51-year-old female patient with left vertebral artery duplication which was detected incidentally.

Duplication of the Left Vertebral Artery Origin: A Case Report

International Nuclear Information System (INIS)

Shin, Sang Wook; Park, Dong Woo; Park, Choong Ki; Lee, Young Jun

2013-01-01

Duplication of vertebral arteries is a very rare but clinically important condition. A duplicated vertebral artery origin can influence hemodynamics, pathogenesis of vascular lesions and treatment options. In cases of vertebral artery duplication, the vertebral arteries generally enter the transverse foramen higher up than normal. Awareness of these vertebral artery variants before procedures, such as neurointervention or surgery, may be beneficial. Here, we describe a case of a 51-year-old female patient with left vertebral artery duplication which was detected incidentally.

Automatic vertebral identification using surface-based registration

Science.gov (United States)

Herring, Jeannette L.; Dawant, Benoit M.

2000-06-01

This work introduces an enhancement to currently existing methods of intra-operative vertebral registration by allowing the portion of the spinal column surface that correctly matches a set of physical vertebral points to be automatically selected from several possible choices. Automatic selection is made possible by the shape variations that exist among lumbar vertebrae. In our experiments, we register vertebral points representing physical space to spinal column surfaces extracted from computed tomography images. The vertebral points are taken from the posterior elements of a single vertebra to represent the region of surgical interest. The surface is extracted using an improved version of the fully automatic marching cubes algorithm, which results in a triangulated surface that contains multiple vertebrae. We find the correct portion of the surface by registering the set of physical points to multiple surface areas, including all vertebral surfaces that potentially match the physical point set. We then compute the standard deviation of the surface error for the set of points registered to each vertebral surface that is a possible match, and the registration that corresponds to the lowest standard deviation designates the correct match. We have performed our current experiments on two plastic spine phantoms and one patient.

Observer agreement in pediatric semiquantitative vertebral fracture diagnosis

Energy Technology Data Exchange (ETDEWEB)

Siminoski, Kerry [University of Alberta, Department of Radiology and Diagnostic Imaging and Division of Endocrinology and Metabolism, Department of Medicine, Edmonton (Canada); Lentle, Brian [University of British Columbia, Department of Radiology, Vancouver (Canada); BC Children' s Hospital, Department of Radiology, Vancouver (Canada); Matzinger, Mary Ann; Shenouda, Nazih [University of Ottawa, Department of Diagnostic Imaging, Ottawa (Canada); Children' s Hospital of Eastern Ontario, Department of Medical Imaging, Ottawa (Canada); Ward, Leanne M. [University of Ottawa, Department of Pediatrics, Children' s Hospital of Eastern Ontario, Ottawa (Canada); Children' s Hospital of Eastern Ontario, Research Institute, Ottawa (Canada); Collaboration: The Canadian STOPP Consortium

2014-04-15

The Genant semiquantitative (GSQ) method has been a standard procedure for diagnosis of vertebral fractures in adults but has only recently been shown to be of clinical utility in children. Observer agreement using the GSQ method in this age group has not been described. To evaluate observer agreement on vertebral readability and vertebral fracture diagnosis using the GSQ method in pediatric vertebral morphometry. Spine radiographs of 186 children with acute lymphoblastic leukemia were evaluated independently by three radiologists using the same GSQ methodology as in adults. A subset of 100 radiographs was evaluated on two occasions. An average of 4.7% of vertebrae were unreadable for the three radiologists. Intraobserver Cohen's kappa (κ) on readability ranged from 0.434 to 0.648 at the vertebral level and from 0.416 to 0.611 at the patient level, while interobserver κ for readability had a range of 0.330 to 0.504 at the vertebral level and 0.295 to 0.467 at the patient level. Intraobserver κ for the presence of vertebral fracture had a range of 0.529 to 0.726 at the vertebral level and was 0.528 to 0.767 at the patient level. Interobserver κ for fracture at the vertebral level ranged from 0.455 to 0.548 and from 0.433 to 0.486 at the patient level. Most κ values for both intra- and interobserver agreement in applying the GSQ method to pediatric spine radiographs were in the moderate to substantial range, comparable to the performance of the technique in adult studies. The GSQ method should be considered for use in pediatric research and clinical practice. (orig.)

Observer agreement in pediatric semiquantitative vertebral fracture diagnosis

International Nuclear Information System (INIS)

Siminoski, Kerry; Lentle, Brian; Matzinger, Mary Ann; Shenouda, Nazih; Ward, Leanne M.

2014-01-01

The Genant semiquantitative (GSQ) method has been a standard procedure for diagnosis of vertebral fractures in adults but has only recently been shown to be of clinical utility in children. Observer agreement using the GSQ method in this age group has not been described. To evaluate observer agreement on vertebral readability and vertebral fracture diagnosis using the GSQ method in pediatric vertebral morphometry. Spine radiographs of 186 children with acute lymphoblastic leukemia were evaluated independently by three radiologists using the same GSQ methodology as in adults. A subset of 100 radiographs was evaluated on two occasions. An average of 4.7% of vertebrae were unreadable for the three radiologists. Intraobserver Cohen's kappa (κ) on readability ranged from 0.434 to 0.648 at the vertebral level and from 0.416 to 0.611 at the patient level, while interobserver κ for readability had a range of 0.330 to 0.504 at the vertebral level and 0.295 to 0.467 at the patient level. Intraobserver κ for the presence of vertebral fracture had a range of 0.529 to 0.726 at the vertebral level and was 0.528 to 0.767 at the patient level. Interobserver κ for fracture at the vertebral level ranged from 0.455 to 0.548 and from 0.433 to 0.486 at the patient level. Most κ values for both intra- and interobserver agreement in applying the GSQ method to pediatric spine radiographs were in the moderate to substantial range, comparable to the performance of the technique in adult studies. The GSQ method should be considered for use in pediatric research and clinical practice. (orig.)

Vascular complications of prosthetic inter-vertebral discs

OpenAIRE

Daly, Kevin J.; Ross, E. Raymond S.; Norris, Heather; McCollum, Charles N.

2006-01-01

Five consecutive cases of prosthetic inter-vertebral disc displacement with severe vascular complications on revisional surgery are described. The objective of this case report is to warn spinal surgeons that major vascular complications are likely with anterior displacement of inter-vertebral discs. We have not been able to find a previous report on vascular complications associated with anterior displacement of prosthetic inter-vertebral discs. In all five patients the prosthetic disc had e...

Constrained vertebrate evolution by pleiotropic genes.

Science.gov (United States)

Hu, Haiyang; Uesaka, Masahiro; Guo, Song; Shimai, Kotaro; Lu, Tsai-Ming; Li, Fang; Fujimoto, Satoko; Ishikawa, Masato; Liu, Shiping; Sasagawa, Yohei; Zhang, Guojie; Kuratani, Shigeru; Yu, Jr-Kai; Kusakabe, Takehiro G; Khaitovich, Philipp; Irie, Naoki

2017-11-01

Despite morphological diversification of chordates over 550 million years of evolution, their shared basic anatomical pattern (or 'bodyplan') remains conserved by unknown mechanisms. The developmental hourglass model attributes this to phylum-wide conserved, constrained organogenesis stages that pattern the bodyplan (the phylotype hypothesis); however, there has been no quantitative testing of this idea with a phylum-wide comparison of species. Here, based on data from early-to-late embryonic transcriptomes collected from eight chordates, we suggest that the phylotype hypothesis would be better applied to vertebrates than chordates. Furthermore, we found that vertebrates' conserved mid-embryonic developmental programmes are intensively recruited to other developmental processes, and the degree of the recruitment positively correlates with their evolutionary conservation and essentiality for normal development. Thus, we propose that the intensively recruited genetic system during vertebrates' organogenesis period imposed constraints on its diversification through pleiotropic constraints, which ultimately led to the common anatomical pattern observed in vertebrates.

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.

Modulación del crecimiento vertebral mediante electrocoagulación hemicircunferencial vertebral asistida

OpenAIRE

Caballero García, Alberto

2011-01-01

Nuestro trabajo está basado en la posibilidad de controlar el desarrollo asimétrico de los cartílagos de crecimiento vertebral, mediante la realización de una fisiodesis hemivertebral, con electrocoagulación, videoasistida por toracoscópica. Se realizará en cinco niveles torácicos, con un abordaje anterior mínimamente invasivo. Por lo tanto, planteamos como hipótesis de trabajo que La destrucción de las fisis de crecimiento vertebral mediante electrocoagulación, videoasistida por vía toracosc...

SpineAnalyzer™ is an accurate and precise method of vertebral fracture detection and classification on dual-energy lateral vertebral assessment scans

International Nuclear Information System (INIS)

Birch, C.; Knapp, K.; Hopkins, S.; Gallimore, S.; Rock, B.

2015-01-01

Osteoporotic fractures of the spine are associated with significant morbidity, are highly predictive of hip fractures, but frequently do not present clinically. When there is a low to moderate clinical suspicion of vertebral fracture, which would not justify acquisition of a radiograph, vertebral fracture assessment (VFA) using Dual-energy X-ray Absorptiometry (DXA) offers a low-dose opportunity for diagnosis. Different approaches to the classification of vertebral fractures have been documented. The aim of this study was to measure the precision and accuracy of SpineAnalyzer™, a quantitative morphometry software program. Lateral vertebral assessment images of 64 men were analysed using SpineAnalyzer™ and standard GE Lunar software. The images were also analysed by two expert readers using a semi-quantitative approach. Agreement between groups ranged from 95.99% to 98.60%. The intra-rater precision for the application of SpineAnalyzer™ to vertebrae was poor in the upper thoracic regions, but good elsewhere. SpineAnalyzer™ is a reproducible and accurate method for measuring vertebral height and quantifying vertebral fractures from VFA scans. - Highlights: • Vertebral fracture assessment (VFA) using Dual-energy X-ray Absorptiometry (DXA) offers a low-dose opportunity for diagnosis. • Agreement between VFA software (SpineAnalyzer™) and expert readers is high. • Intra-rater precision of SpineAnalyzer™ applied to upper thoracic vertebrae is poor, but good elsewhere. • SpineAnalyzer™ is reproducible and accurate for vertebral height measurement and fracture quantification from VFA scans

Influence of physical activity on vertebral strength during late adolescence.

Science.gov (United States)

Junno, Juho-Antti; Paananen, Markus; Karppinen, Jaro; Tammelin, Tuija; Niinimäki, Jaakko; Lammentausta, Eveliina; Niskanen, Markku; Nieminen, Miika T; Järvelin, Marjo-Riitta; Takatalo, Jani; Tervonen, Osmo; Tuukkanen, Juha

2013-02-01

Reduced vertebral strength is a clear risk factor for vertebral fractures. Men and women with vertebral fractures often have reduced vertebral size and bone mineral density (BMD). Vertebral strength is controlled by both genetic and developmental factors. Malnutrition and low levels of physical activity are commonly considered to result in reduced bone size during growth. Several studies have also demonstrated the general relationship between BMD and physical activity in the appendicular skeleton. In this study, we wanted to clarify the role of physical activity on vertebral bodies. Vertebral dimensions appear to generally be less pliant than long bones when lifetime changes occur. We wanted to explore the association between physical activity during late adolescence and vertebral strength parameters such as cross-sectional size and BMD. The association between physical activity and vertebral strength was explored by measuring vertebral strength parameters and defining the level of physical activity during adolescence. The study population consisted of 6,928 males and females who, at 15 to 16 and 19 years of age, responded to a mailed questionnaire inquiring about their physical activity. A total of 558 individuals at the mean age of 21 years underwent magnetic resonance imaging (MRI) scans. We measured the dimensions of the fourth lumbar vertebra from the MRI scans of the Northern Finland Birth Cohort 1986 and performed T2* relaxation time mapping, reflective of BMD. Vertebral strength was based on these two parameters. We analyzed the association of physical activity on vertebral strength using the analysis of variance. We observed no association between the level of physical activity during late adolescence and vertebral strength at 21 years. Copyright © 2013 Elsevier Inc. All rights reserved.

Rehabilitation in osteoporotic vertebral fractures

OpenAIRE

Pratelli, Elisa; Cinotti, Irene; Pasquetti, Pietro

2010-01-01

Vertebral fractures occur particularly in osteoporotic patients due to an increased bone fragility. Vertebral fractures influence the quality of life, mobility and mortality. Preventive training exercises and proprioception reeducation can be utilised for improving posture, balance and level of daily function and for decreasing pain. Quality of life is improved even beyond the active training period. This mini review provides information based on the literature for the rehabilitation of osteo...

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

CT and MRI characteristics of vertebral tuberculosis (34 cases)

International Nuclear Information System (INIS)

Lu Wenbing; Liao Qinghou; Wu Shiqiang; Huang Tao; Deng Yufang; Liu Jianming

2007-01-01

Objective: To explore CT and MRI characteristics of vertebral tuberculosis. Methods: 34 patients with vertebral tuberculosis proved by clinic or pathology were analyzed retrospectively. Of these patients, 20 were performed with CT examination and 24 with MRI, 10 with both CT and MRI. The results were compared mutually. Results: The CT features of vertebral tuberculosis were bone destruction, paraspinal abscess, spinal canal involvement. The MRI features of vertebral tuberculosis were bone destruction, intervertebral disc destruction, paraspinal abscess, spinal canal involvement, sub-ligamental spread. Conclusion: Vertebral tuberculosis showed multiple characteristics on CT and MRI. CT is useful in showing sequester and calcification, and MRI is useful in showing sub-ligamental spread, epidural and spinal cord involvement. Combining CT with and MRI is helpful for the diagnosis and differential diagnosis of vertebral tuberculosis. (authors)

Facultative parthenogenesis in vertebrates: reproductive error or chance?

Science.gov (United States)

Lampert, K P

2008-01-01

Parthenogenesis, the development of an embryo from a female gamete without any contribution of a male gamete, is very rare in vertebrates. Parthenogenetically reproducing species have, so far, only been found in the Squamate reptiles (lizards and snakes). Facultative parthenogenesis, switching between sexual and clonal reproduction, although quite common in invertebrates, e.g. Daphnia and aphids, seems to be even rarer in vertebrates. However, isolated cases of parthenogenetic development have been reported in all vertebrate groups. Facultative parthenogenesis in vertebrates has only been found in captive animals but might simply have been overlooked in natural populations. Even though its evolutionary impact is hard to determine and very likely varies depending on the ploidy restoration mechanisms and sex-determining mechanisms involved, facultative parthenogenesis is already discussed in conservation biology and medical research. To raise interest for facultative parthenogenesis especially in evolutionary biology, I summarize the current knowledge about facultative parthenogenesis in the different vertebrate groups, introduce mechanisms of diploid oocyte formation and discuss the genetic consequences and potential evolutionary impact of facultative parthenogenesis in vertebrates.

Ancient deuterostome origins of vertebrate brain signalling centres.

Science.gov (United States)

Pani, Ariel M; Mullarkey, Erin E; Aronowicz, Jochanan; Assimacopoulos, Stavroula; Grove, Elizabeth A; Lowe, Christopher J

2012-03-14

Neuroectodermal signalling centres induce and pattern many novel vertebrate brain structures but are absent, or divergent, in invertebrate chordates. This has led to the idea that signalling-centre genetic programs were first assembled in stem vertebrates and potentially drove morphological innovations of the brain. However, this scenario presumes that extant cephalochordates accurately represent ancestral chordate characters, which has not been tested using close chordate outgroups. Here we report that genetic programs homologous to three vertebrate signalling centres-the anterior neural ridge, zona limitans intrathalamica and isthmic organizer-are present in the hemichordate Saccoglossus kowalevskii. Fgf8/17/18 (a single gene homologous to vertebrate Fgf8, Fgf17 and Fgf18), sfrp1/5, hh and wnt1 are expressed in vertebrate-like arrangements in hemichordate ectoderm, and homologous genetic mechanisms regulate ectodermal patterning in both animals. We propose that these genetic programs were components of an unexpectedly complex, ancient genetic regulatory scaffold for deuterostome body patterning that degenerated in amphioxus and ascidians, but was retained to pattern divergent structures in hemichordates and vertebrates. © 2012 Macmillan Publishers Limited. All rights reserved

X-ray image segmentation for vertebral mobility analysis

International Nuclear Information System (INIS)

Benjelloun, Mohammed; Mahmoudi, Said

2008-01-01

The goal of this work is to extract the parameters determining vertebral motion and its variation during flexion-extension movements using a computer vision tool for estimating and analyzing vertebral mobility. To compute vertebral body motion parameters we propose a comparative study between two segmentation methods proposed and applied to lateral X-ray images of the cervical spine. The two vertebra contour detection methods include (1) a discrete dynamic contour model (DDCM) and (2) a template matching process associated with a polar signature system. These two methods not only enable vertebra segmentation but also extract parameters that can be used to evaluate vertebral mobility. Lateral cervical spine views including 100 views in flexion, extension and neutral orientations were available for evaluation. Vertebral body motion was evaluated by human observers and using automatic methods. The results provided by the automated approaches were consistent with manual measures obtained by 15 human observers. The automated techniques provide acceptable results for the assessment of vertebral body mobility in flexion and extension on lateral views of the cervical spine. (orig.)

Varied overstrain injuries of the vertebral column conditioned by evolution

Energy Technology Data Exchange (ETDEWEB)

Kohlbach, W

1983-08-01

During physiological growth of the juvenile vertebral column, various stages of stability occur which are characterized by the condition of the marginal rim of the vertebral bodies. If the vertebral juvenile column is overstrained, these variations in stability results in a variety of damage to vertebral bodies and vertebral disks. One of these lesions corresponds to Scheuermann's disease (osteochondrosis of vertebral epiphyses in juveniles). Damage of the vertebral column due to overstrain can occur only if the overstrain is applied in upright position. Since Man alone can damage his vertebral column in upright position (as a result of his evolutionary development), Scheuermann's thesis is confirmed that Scheuermann's disease is confined to Man. Spondylolysis/spondylolisthesis is also a damage caused by overstrain. Here, too, the damage can occur only if the load is exercised in upright position, with the exception of a slanted positioning of the intervertebral components.

Varied overstrain injuries of the vertebral column conditioned by evolution

International Nuclear Information System (INIS)

Kohlbach, W.

1983-01-01

During physiological growth of the juvenile vertebral column, various stages of stability occur which are characterized by the condition of the marginal rim of the vertebral bodies. If the vertebral juvenile column is overstrained, these variations in stability results in a variety of damage to vertebral bodies and vertebral disks. One of these lesions corresponds to Scheuermann's disease (osteochondrosis of vertebral epiphyses in juveniles). Damage of the vertebral column due to overstrain can occur only if the overstrain is applied in upright position. Since Man alone can damage his vertebral column in upright position (as a result of his evolutionary development), Scheuermann's thesis is confirmed that Scheuermann's disease is confined to Man. Spondylolysis/spondylolisthesis is also a damage caused by overstrain. Here, too, the damage can occur only if the load is exercised in upright position, with the exception of a slanted positioning of the intervertebral components. (orig.) [de

The prevalence of radiographic vertebral fractures in Latin American countries: the Latin American Vertebral Osteoporosis Study (LAVOS).

Science.gov (United States)

Clark, P; Cons-Molina, F; Deleze, M; Ragi, S; Haddock, L; Zanchetta, J R; Jaller, J J; Palermo, L; Talavera, J O; Messina, D O; Morales-Torres, J; Salmeron, J; Navarrete, A; Suarez, E; Pérez, C M; Cummings, S R

2009-02-01

In the first population-based study of vertebral fractures in Latin America, we found a 11.18 (95% CI 9.23-13.4) prevalence of radiographically ascertained vertebral fractures in a random sample of 1,922 women from cities within five different countries. These figures are similar to findings from studies in Beijing, China, some regions of Europe, and slightly lower than those found in the USA using the same standardized methodology. We report the first study of radiographic vertebral fractures in Latin America. An age-stratified random sample of 1,922 women aged 50 years and older from Argentina, Brazil, Colombia, Mexico, and Puerto Rico were included. In all cases a standardized questionnaire and lateral X-rays of the lumbar and thoracic spine were obtained after informed consent. A standardized prevalence of 11.18 (95% CI 9.23-13.4) was found. The prevalence was similar in all five countries, increasing from 6.9% (95% CI 4.6-9.1) in women aged 50-59 years to 27.8% (95% CI 23.1-32.4) in those 80 years and older (p for trend < 0.001). Among different risk factors, self-reported height loss OR = 1.63 (95% CI: 1.18-2.25), and previous history of fracture OR = 1.52 (95% CI: 1.14-2.03) were significantly (p < 0.003 and p < 0.04 respectably) associated with the presence of radiographic vertebral fractures in the multivariate analysis. In the bivariate analyses HRT was associated with a 35% lower risk OR = 0.65 (95% CI: 0.46-0.93) and physical activity with a 27% lower risk of having a vertebral fracture OR = 0.73 (95% CI: 0.55-0.98), but were not statistically significant in multivariate analyses We conclude that radiographically ascertained vertebral fractures are common in Latin America. Health authorities in the region should be aware and consider implementing measures to prevent vertebral fractures.

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

Prevalence of thoracolumbar vertebral fractures on multidetector CT

International Nuclear Information System (INIS)

Bartalena, Tommaso; Giannelli, Giovanni; Rinaldi, Maria Francesca; Rimondi, Eugenio; Rinaldi, Giovanni; Sverzellati, Nicola; Gavelli, Giampaolo

2009-01-01

Objective: To evaluate the prevalence of osteoporotic vertebral fractures in patients undergoing multidetector computed tomography (MDCT) of the chest and/or abdomen. Materials and methods: 323 consecutive patients (196 males, 127 females) with a mean age of 62.6 years (range 20-88) who had undergone chest and/or abdominal MDCT were evaluated. Sagittal reformats of the spine obtained from thin section datasets were reviewed by two radiologists and assessed for vertebral fractures. Morphometric analysis using electronic calipers was performed on vertebral bodies which appeared abnormal upon visual inspection. A vertebral body height loss of 15% or more was considered a fracture and graded as mild (15-24%), moderate (25-49%) or severe (more than 50%). Official radiology reports were reviewed and whether the vertebral fractures had been reported or not was noted. Results: 31 out of 323 patients (9.5%) had at least 1 vertebral fracture and 7 of those patients had multiple fractures for a total of 41 fractures. Morphometric grading revealed 10 mild, 16 moderate and 15 severe fractures. Prevalence was higher in women (14.1%) than men (6.6%) and increased with patients age with a 17.1% prevalence in post-menopausal women. Only 6 out 41 vertebral fractures (14.6%) had been noted in the radiology final report while the remaining 35 (85.45) had not. Conclusion: although vertebral fractures represent frequent incidental findings on multidetector CT studies and may be easily identified on sagittal reformats, they are often underreported by radiologists, most likely because of unawareness of their clinical importance.

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.

Reproducibility of central lumbar vertebral BMD

International Nuclear Information System (INIS)

Chan, F.; Pocock, N.; Griffiths, M.; Majerovic, Y.; Freund, J.

1997-01-01

Full text: Lumbar vertebral bone mineral density (BMD) using dual X-ray absorptiometry (DXA) has generally been calculated from a region of interest which includes the entire vertebral body. Although this region excludes part of the transverse processes, it does include the outer cortical shell of the vertebra. Recent software has been devised to calculate BMD in a central vertebral region of interest which excludes the outer cortical envelope. Theoretically this area may be more sensitive to detecting osteoporosis which affects trabecular bone to a greater extent than cortical bone. Apart from the sensitivity of BMD estimation, the reproducibility of any measurement is important owing to the slow rate of change of bone mass. We have evaluated the reproducibility of this new vertebral region of interest in 23 women who had duplicate lumbar spine DXA scans performed on the same day. The patients were repositioned between each measurement. Central vertebral analysis was performed for L2-L4 and the reproducibility of area, bone mineral content (BMC) and BMD calculated as the coefficient of variation; these values were compared with those from conventional analysis. Thus we have shown that the reproducibility of the central BMD is comparable to the conventional analysis which is essential if this technique is to provide any additional clinical data. The reasons for the decrease in reproducibility of the area and hence BMC requires further investigation

Varied overstrain injuries of the vertebral column conditioned by evolution

Energy Technology Data Exchange (ETDEWEB)

Kohlbach, W.

1983-08-01

During physiological growth of the juvenile vertebral column, various stages of stability occur which are characterized by the condition of the marginal rim of the vertebral bodies. If the vertebral juvenile column is overstrained, these variations in stability results in a variety of damage to vertebral bodies and vertebral disks. One of these lesions corresponds to Scheuermann's disease (osteochondrosis of vertebral epiphyses in juveniles). Damage of the vertebral column due to overstrain can occur only if the overstrain is applied in upright position. Since Man alone can damage his vertebral column in upright position (as a result of his evolutionary development), Scheuermann's thesis is confirmed that Scheuermann's disease is confined to Man. Spondylolysis/spondylolisthesis is also a damage caused by overstrain. Here, too, the damage can occur only if the load is exercised in upright position, with the exception of a slanted positioning of the intervertebral components.

High-altitude adaptations in vertebrate hemoglobins

DEFF Research Database (Denmark)

Weber, Roy E.

2007-01-01

Vertebrates at high altitude are subjected to hypoxic conditions that challenge aerobic metabolism. O2 transport from the respiratory surfaces to tissues requires matching between the O2 loading and unloading tensions and theO2-affinity of blood, which is an integrated function of hemoglobin......, birds and ectothermic vertebrates at high altitude....

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.

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

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

Differential muscle regulatory factor gene expression between larval and adult myogenesis in the frog Xenopus laevis: adult myogenic cell-specific myf5 upregulation and its relation to the notochord suppression of adult muscle differentiation.

Science.gov (United States)

Yamane, Hitomi; Nishikawa, Akio

2013-08-01

During Xenopus laevis metamorphosis, larval-to-adult muscle conversion depends on the differential responses of adult and larval myogenic cells to thyroid hormone. Essential differences in cell growth, differentiation, and hormone-dependent life-or-death fate have been reported between cultured larval (tail) and adult (hindlimb) myogenic cells. A previous study revealed that tail notochord cells suppress terminal differentiation in adult (but not larval) myogenic cells. However, little is known about the differences in expression patterns of myogenic regulatory factors (MRF) and the satellite cell marker Pax7 between adult and larval myogenic cells. In the present study, we compared mRNA expression of these factors between the two types. At first, reverse transcription polymerase chain reaction analysis of hindlimb buds showed sequential upregulation of myf5, myogenin, myod, and mrf4 during stages 50-54, when limb buds elongate and muscles begin to form. By contrast, in the tail, there was no such increase during the same period. Secondary, these results were duplicated in vitro: adult myogenic cells upregulated myf5, myod, and pax7 in the early culture period, followed by myogenin upregulation and myotube differentiation, while larval myogenic cells did not upregulate these genes and precociously started myotube differentiation. Thirdly, myf5 upregulation and early-phase proliferation in adult myogenic cells were potently inhibited by the presence of notochord cells, suggesting that notochord cells suppress adult myogenesis through inhibiting the transition from Myf5(-) stem cells to Myf5(+) committed myoblasts. All of the data presented here suggest that myf5 upregulation can be a good criterion for the activation of adult myogenesis during X. laevis metamorphosis.

Vertebral body osteomyelitis in the horse

International Nuclear Information System (INIS)

Markel, M.D.; Madigan, J.E.; Lichtensteiger, C.A.; Large, S.M.; Hornof, W.J.

1986-01-01

The clinical signs, laboratory data, results of nuclear scintigraphy and radiographic examination of five horses with vertebral body osteomyelitis are described together with response to treatment. Three horses were less than five months of age. Four horses demonstrated hindlimb paresis and in three a focus of pain in the thoracolumbar region could be identified. An umbilical abscess, a caudal lobe lung abscess and a patent urachus were considered primary niduses of infection in each of three horses. Leucocytosis, neutrophilia, anaemia and elevated fibrinogen were the most consistent laboratory abnormalities. Nuclear scintigraphy was performed in three horses and identified the site of the vertebral lesion which was subsequently evaluated radiographically. In the other two horses radiographic examination in the region of areas of focal pain identified a lesion. Radiographic abnormalities included compression fractures of vertebral bodies (two), proliferative new bone (three) and soft tissue swelling ventral to a vertebral body (one). Two horses, including one with a compression fracture of the second lumbar vertebra, received parenteral antimicrobial therapy for 40 and 74 days, respectively. When re-examined six months later they showed no neurological abnormalities. The other three horses failed to respond to antimicrobial treatment and were humanely destroyed. The horse with a lung abscess also had an abscess cranial to the right tuber coxae which extended into the vertebral bodies of the third and fourth lumbar vertebrae from which Streptococcus zooepidemicus was cultured. A horse with proliferative new bone on the ventral aspect of the fifth and sixth thoracic vertebrae had a mediastinal mass associated with these vertebrae and fungal granulomas, from which Aspergillus species was cultured, in the heart and aorta, trachea, spleen and kidney. The horse with a patent urachus and soft tissue swelling ventral to the vertebral body of the 12th thoracic vertebra

Osteomielitis vertebral piógena Pyogenic vertebral osteomyelitis

Directory of Open Access Journals (Sweden)

Pedro P. Perrotti

2009-10-01

Full Text Available La osteomielitis vertebral piógena (OVP es una localización poco frecuente (2-7% Se confirma con el aislamiento de un microorganismo de una vértebra, disco intervertebral, absceso epidural o paravertebral. Se describe una serie de casos por la infrecuente presentación de esta enfermedad, que puede ser consulta inicial en los servicios de clínica médica y por su sintomatología inespecífica que supone una dificultad diagnóstica. Tanto la columna lumbar como la dorsal fueron los sitios más afectados. El dolor dorsolumbar y la paraparesia fueron los síntomas más frecuentes de presentación. En ocho pacientes se aislaron Staphylococcus aureus, en uno Escherichia coli y en el restante Haemophylus sp. Se observó leucocitosis sólo en tres pacientes, y en dos velocidad de sedimentación globular mayor de 100 mm/h. Los diez pacientes presentaron imágenes características de osteomielitis vertebral piógena en la resonancia nuclear magnética. Dentro de las complicaciones, los abscesos paravertebrales y epidurales fueron los más frecuentes (en cinco enfermos. Además, un paciente presentó empiema pleural. De los diez pacientes de esta serie, siete recibieron inicialmente tratamiento médico empírico y luego específico para el germen aislado. En los restantes el tratamiento fue guiado de acuerdo al antibiograma. A dos enfermos fue necesario realizarles laminectomía descompresiva por compromiso de partes blandas y a otros dos estabilización quirúrgica por inestabilidad espinal, observándose buena evolución en todos los casos. Esta serie demuestra que, ante un paciente con dolor dorsolumbar y síntomas neurológicos se deberá tener en cuenta esta entidad para evitar un retraso en el tratamiento.Pyogenic osteomyelitis seldom affects the spine (2-7%. It is diagnosed by the isolation of a bacterial agent in the vertebral body, the intervertebral disks or from paravertebral or epidural abscesses. We report a retrospective study of ten

VerSeDa: vertebrate secretome database.

Science.gov (United States)

Cortazar, Ana R; Oguiza, José A; Aransay, Ana M; Lavín, José L

2017-01-01

Based on the current tools, de novo secretome (full set of proteins secreted by an organism) prediction is a time consuming bioinformatic task that requires a multifactorial analysis in order to obtain reliable in silico predictions. Hence, to accelerate this process and offer researchers a reliable repository where secretome information can be obtained for vertebrates and model organisms, we have developed VerSeDa (Vertebrate Secretome Database). This freely available database stores information about proteins that are predicted to be secreted through the classical and non-classical mechanisms, for the wide range of vertebrate species deposited at the NCBI, UCSC and ENSEMBL sites. To our knowledge, VerSeDa is the only state-of-the-art database designed to store secretome data from multiple vertebrate genomes, thus, saving an important amount of time spent in the prediction of protein features that can be retrieved from this repository directly. VerSeDa is freely available at http://genomics.cicbiogune.es/VerSeDa/index.php. © The Author(s) 2017. Published by Oxford University Press.

Kyphoplasty for severe osteoporotic vertebral compression fractures

International Nuclear Information System (INIS)

Bao Zhaohua; Wang Genlin; Yang Huilin; Meng Bin; Chen Kangwu; Jiang Weimin

2010-01-01

Objective: To evaluate the clininal efficacy of kyphoplasty for severe osteoporotic vertebral compression fractures. Methods: Forty-five patients with severe osteoporotic compressive fractures were treated by kyphoplasty from Jan 2005 to Jan 2009. The compressive rate of the fractured vertebral bodies was more than 75%. According to the morphology of the vertebral compression fracture bodies the unilateral or bilateral balloon kyphoplasty were selected. The anterior vertebral height was measured on a standing lateral radiograph at pre-operative, post-operative (one day after operation) and final follow-up time. A visual analog scale(VAS) and the Oswestry disability index (ODI) were chosen to evaluate pain status and functional activity. Results: The mean follow-up was for 21.7 months (in range from 18 to 48 months). The anterior vertebral body height of fracture vertebra was restored from preoperative (18.7 ± 3.1)% to postoperative (51.4 ± 2.3)%, the follow-up period (50.2 ± 2.7)%. There was a significant improvement between preoperative and postoperative values (P 0.05). The VAS was 8.1 ± 1.4 at preoperative, 2.6 ± 0.9 at postoperative, 2.1 ± 0.5 at final follow-up time; and the ODI was preoperative 91.1 ± 2.3, postoperative 30.7 ± 7.1, follow-up period 26.1 ± 5.1. There was statistically significant improvement in the VAS and ODI in the post-operative assessment compared with the pre-operative assessment (P 0.05). Asymptomatic cement leakage occurred in three cases. New vertebral fracture occurred in one case. Conclusion: The study suggests that balloon kyphoplasty is a safe and effective procedure in the treatment of severe osteoporotic vertebral compression fractures. (authors)

The pre-vertebrate origins of neurogenic placodes.

Science.gov (United States)

Abitua, Philip Barron; Gainous, T Blair; Kaczmarczyk, Angela N; Winchell, Christopher J; Hudson, Clare; Kamata, Kaori; Nakagawa, Masashi; Tsuda, Motoyuki; Kusakabe, Takehiro G; Levine, Michael

2015-08-27

The sudden appearance of the neural crest and neurogenic placodes in early branching vertebrates has puzzled biologists for over a century. These embryonic tissues contribute to the development of the cranium and associated sensory organs, which were crucial for the evolution of the vertebrate "new head". A previous study suggests that rudimentary neural crest cells existed in ancestral chordates. However, the evolutionary origins of neurogenic placodes have remained obscure owing to a paucity of embryonic data from tunicates, the closest living relatives to those early vertebrates. Here we show that the tunicate Ciona intestinalis exhibits a proto-placodal ectoderm (PPE) that requires inhibition of bone morphogenetic protein (BMP) and expresses the key regulatory determinant Six1/2 and its co-factor Eya, a developmental process conserved across vertebrates. The Ciona PPE is shown to produce ciliated neurons that express genes for gonadotropin-releasing hormone (GnRH), a G-protein-coupled receptor for relaxin-3 (RXFP3) and a functional cyclic nucleotide-gated channel (CNGA), which suggests dual chemosensory and neurosecretory activities. These observations provide evidence that Ciona has a neurogenic proto-placode, which forms neurons that appear to be related to those derived from the olfactory placode and hypothalamic neurons of vertebrates. We discuss the possibility that the PPE-derived GnRH neurons of Ciona resemble an ancestral cell type, a progenitor to the complex neuronal circuit that integrates sensory information and neuroendocrine functions in vertebrates.

Vertebral Column Resection for Rigid Spinal Deformity.

Science.gov (United States)

Saifi, Comron; Laratta, Joseph L; Petridis, Petros; Shillingford, Jamal N; Lehman, Ronald A; Lenke, Lawrence G

2017-05-01

Broad narrative review. To review the evolution, operative technique, outcomes, and complications associated with posterior vertebral column resection. A literature review of posterior vertebral column resection was performed. The authors' surgical technique is outlined in detail. The authors' experience and the literature regarding vertebral column resection are discussed at length. Treatment of severe, rigid coronal and/or sagittal malalignment with posterior vertebral column resection results in approximately 50-70% correction depending on the type of deformity. Surgical site infection rates range from 2.9% to 9.7%. Transient and permanent neurologic injury rates range from 0% to 13.8% and 0% to 6.3%, respectively. Although there are significant variations in EBL throughout the literature, it can be minimized by utilizing tranexamic acid intraoperatively. The ability to correct a rigid deformity in the spine relies on osteotomies. Each osteotomy is associated with a particular magnitude of correction at a single level. Posterior vertebral column resection is the most powerful posterior osteotomy method providing a successful correction of fixed complex deformities. Despite meticulous surgical technique and precision, this robust osteotomy technique can be associated with significant morbidity even in the most experienced hands.

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

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

Vertebrate Embryonic Cleavage Pattern Determination.

Science.gov (United States)

Hasley, Andrew; Chavez, Shawn; Danilchik, Michael; Wühr, Martin; Pelegri, Francisco

2017-01-01

The pattern of the earliest cell divisions in a vertebrate embryo lays the groundwork for later developmental events such as gastrulation, organogenesis, and overall body plan establishment. Understanding these early cleavage patterns and the mechanisms that create them is thus crucial for the study of vertebrate development. This chapter describes the early cleavage stages for species representing ray-finned fish, amphibians, birds, reptiles, mammals, and proto-vertebrate ascidians and summarizes current understanding of the mechanisms that govern these patterns. The nearly universal influence of cell shape on orientation and positioning of spindles and cleavage furrows and the mechanisms that mediate this influence are discussed. We discuss in particular models of aster and spindle centering and orientation in large embryonic blastomeres that rely on asymmetric internal pulling forces generated by the cleavage furrow for the previous cell cycle. Also explored are mechanisms that integrate cell division given the limited supply of cellular building blocks in the egg and several-fold changes of cell size during early development, as well as cytoskeletal specializations specific to early blastomeres including processes leading to blastomere cohesion. Finally, we discuss evolutionary conclusions beginning to emerge from the contemporary analysis of the phylogenetic distributions of cleavage patterns. In sum, this chapter seeks to summarize our current understanding of vertebrate early embryonic cleavage patterns and their control and evolution.

Vertebral metastases: characteristic MRI findings due to epidural carcinomatous inflitration

International Nuclear Information System (INIS)

Hutzelmann, A.; Palmie, S.; Freund, M.

1997-01-01

Purpose: In cases of lumbar vertebral metastasis associated with anterior epidural carcinomatous infiltration, we have observed that infiltrations tend to respect the midline. This study led to the systematic recognition of these phenomena in vertebral metastases. Materials and Methods: 11 Patients with 17 vertebral metastases and adjacent anterior epidural infiltration were reviewed retrospectively. All cases were studied by MRI. The routinely used imaging technique included spin echo (SE) T 1 and T 2 weighted sequences in the sagittal plane native and T 1 -SE without and with Gd-DTPA in the axial planes. The radiological findings of these phenomena and the anatomy were studied. Results: We observed these phenomena to be uni- or bilateral in 88.3% of all cases with intraspinal anterior epidural carcinomatous infiltration, especially in that part of the vertebral body where the basal vertebral venous plexus was located. Conclusion: We conclude that vertebral metastases respect the midline. We interpret this fact as being due the anatomy of the vertebral body and especially its stabilization by the posterior longitudinal ligament. These findings may be helpful in the differential diagnosis of vertebral body metastases with epidural infiltration in contrast to intraspinal processes which proceed with the destruction of the vertebral body. (orig.) [de

Stent assisted coil embolization of a dissecting aneurysm of the vertebral artery: a case involving a patient with hypoplasia of the contralateral vertebral artery

International Nuclear Information System (INIS)

Kim, Hyun Jin; Jeong, Hae Woong; Cho, Jae Kwoeng; Park, Jeong Hoon; Koo, Yong Woon; Baik, Seung Kug

2002-01-01

A dissecting aneurysm of the vertebral artery may be treated conservatively, surgically, or using an endovascular approach. Proximal clipping, wrapping or trapping are surgical treatment methods, and endovascular treatment with coils and balloons is performed where a dissecting aneurysm is located near the midline or the appropriate surgical manipulation is difficult. As the contralateral vertebral artery of this patient was hypoplastic, the stent-assisted coil embolization technique was employed to preserve the ipsilateral vertebral artery. We describe a clinical case of dissecting aneurysm of the vertebral artery occurring in a patient in whom a hypoplastic contralateral vertebral artery was successfully treated

Symptomatic intracranial vertebral artery atherosclerotic stenosis (≥70%) with concurrent contralateral vertebral atherosclerotic diseases in 88 patients treated with the intracranial stenting

Energy Technology Data Exchange (ETDEWEB)

Wang, Zi-Liang [Stroke Center, Henan Provincial People’s Hospital, Zhengzhou University (China); Gao, Bu-Lang [Department of Medical Research Shijiazhuang First Hospital, Hebei Medical University (China); Li, Tian-Xiao, E-mail: litianxiaod@163.com [Stroke Center, Henan Provincial People’s Hospital, Zhengzhou University (China); Cai, Dong-Yang; Zhu, Liang-Fu; Bai, Wei-Xing; Xue, Jiang-Yu; Li, Zhao-Shuo [Stroke Center, Henan Provincial People’s Hospital, Zhengzhou University (China)

2015-09-15

Highlights: • Symptomatic vertebral artery stenosis can be treated with intracranial stenting. • Stenting for intracranial vertebral artery stenosis is safe and effective. • Stenting for intracranial vertebral artery stenosis can prevent long-term stroke. - Abstract: Purpose: To investigate the safety, effect and instent restenosis rate of Wingspan stenting in treating patients with intracranial vertebral artery atherosclerotic stenosis (70–99%) concurrent with contralateral vertebral artery atherosclerotic diseases. Materials and methods: Eighty-eight patients with severe symptomatic intracranial vertebral artery atherosclerotic stenosis (≥70%) combined with contralateral vertebral artery atherosclerotic diseases were treated with the Wingpsan stent. All the baseline, cerebral angiography, success rate, perioperative complications, clinical and imaging follow-up data were prospectively analyzed. Results: The success rate of stenting was 100%, and the mean stenotic rate was reduced from prestenting (84.9 ± 6.8)% to poststenting (17.2 ± 5.9)%. The perioperative stroke rate was 1.1%. Among eighty patients (90.9%) with clinical follow-up 8-62 months (mean 29.3 ± 17.2) poststenting, five (6.3%) had posterior circulation TIA only, three (3.8%) had mild stroke in the posterior circulation but recovered completely, and another five patients greater than 70 years old died of non-ischemic stroke. Imaging follow-up in 46 patients (52.3%) 5–54 months (mean 9.9 ± 9.9) following stenting revealed instent restenosis in 12 patients (26.1%) including 7 (58.3%) symptomatic restenosis. Age and residual stenosis were the two factors to significantly (P < 0.05) affect instent restenosis. Conclusion: Wingspan stenting in the intracranial vertebral artery atherosclerotic stenosis combined with contralateral vertebral artery atherosclerotic diseases has a low perioperative stroke rate and a good preventive effect on long-term ischemic stroke, but the instent restenosis

Congenital abnormalities of the vertebral column in ferrets.

Science.gov (United States)

Proks, Pavel; Stehlik, Ladislav; Paninarova, Michaela; Irova, Katarina; Hauptman, Karel; Jekl, Vladimir

2015-01-01

Vertebral column pathologies requiring surgical intervention have been described in pet ferrets, however little information is available on the normal vertebral formula and congenital variants in this species. The purpose of this retrospective study was to describe vertebral formulas and prevalence of congenital vertebral anomalies in a sample of pet ferrets. Radiographs of 172 pet ferrets (96 males and 76 females) were included in this retrospective study. In 143 ferrets (83.14%), five different formulas of the vertebral column were recorded with normal morphology of vertebrae (rib attachment included) but with a variable number of thoracic (Th), lumbar (L), and sacral (S) vertebrae. The number of cervical (C) vertebrae was constant in all examined animals. Observed vertebral formulas were C7/Th14/L6/S3 (51.74%), C7/Th14/L6/S4 (22.10%), C7/Th14/L7/S3 (6.98%), C7/Th15/L6/S3 (1.74%), and C7/Th15/L6/S4 (0.58%). Formula C7/Th14/L6/S4 was significantly more common in males than in females (P < 0.05). Congenital spinal abnormalities were found in 29 ferrets (16.86%), mostly localized in the thoracolumbar and lumbosacral regions. The cervical region was affected in only one case. Transitional vertebrae represented the most common congenital abnormalities (26 ferrets) in the thoracolumbar (13 ferrets) and lumbosacral regions (10 ferrets) or simultaneously in both regions (three ferrets). Other vertebral anomalies included block (two ferrets) and wedge vertebra (one ferret). Spina bifida was not detected. Findings from the current study indicated that vertebral formulas may vary in ferrets and congenital abnormalities are common. This should be taken into consideration for surgical planning. © 2014 American College of Veterinary Radiology.

Kyphoplasty for vertebral augmentation in the elderly with osteoporotic vertebral compression fractures: scenarios and review of recent studies.

Science.gov (United States)

Bednar, Timothy; Heyde, Christoph E; Bednar, Grace; Nguyen, David; Volpi, Elena; Przkora, Rene

2013-11-01

Vertebral compression fractures caused by osteoporosis are among the most common fractures in the elderly. The treatment focuses on pain control, maintenance of independence, and management of the osteoporosis. Elderly patients often encounter adverse effects to pain medications, do not tolerate bed rest, and are not ideal candidates for invasive spinal reconstructive surgery. Percutaneous vertebral augmentation (vertebroplasty or kyphoplasty) has become popular as a less-invasive alternative. However, studies have questioned the effectiveness of these procedures. The authors conducted a MEDLINE search using relevant search terms including osteoporosis, osteoporotic vertebral compression fracture, elderly, kyphoplasty and vertebroplasty. Two elderly patients presented with a fracture of their third and first lumbar vertebral body, respectively. One patient progressed well with conservative treatment, whereas the other patient was hospitalized secondary to pain after conservative measures failed to offer improvement. The hospitalized patient subsequently opted for a kyphoplasty and was able to resume his normal daily activities after the procedure. Selecting patients on an individual case-by-case basis can optimize the effectiveness and outcomes of a vertebral augmentation. This process includes the documentation of an osteoporotic vertebral compression fracture with the aide of imaging studies, including the acuity of the fracture as well as the correlation with the physical examination findings. Patients who are functional and improving under a conservative regimen are not candidates for kyphoplasty. However, if the conservative management is not successful after 4 to 6 weeks and the patient is at risk to become bedridden, an augmentation should be considered. A kyphoplasty procedure may be preferred over vertebroplasty, given the lower risk profile and better outcomes regarding spinal alignment. Published by Elsevier HS Journals, Inc.

Non-contiguous multifocal vertebral osteomyelitis caused by Serratia marcescens.

Science.gov (United States)

Lau, Jen Xin; Li, Jordan Yuanzhi; Yong, Tuck Yean

2015-03-01

Serratia marcescens is a common nosocomial infection but a rare cause of osteomyelitis and more so of vertebral osteomyelitis. Vertebral osteomyelitis caused by this organism has been reported in few studies. We report a case of S. marcescens vertebral discitis and osteomyelitis affecting multiple non-contiguous vertebras. Although Staphylococcus aureus is the most common cause of vertebral osteomyelitis, rare causes, such as S. marcescens, need to be considered, especially when risk factors such as intravenous heroin use, post-spinal surgery and immunosuppression are present. Therefore, blood culture and where necessary biopsy of the infected region should be undertaken to establish the causative organism and determine appropriate antibiotic susceptibility. Prompt diagnosis of S. marcescens vertebral osteomyelitis followed by the appropriate treatment can achieve successful outcomes.

Handed behavior in hagfish--an ancient vertebrate lineage--and a survey of lateralized behaviors in other invertebrate chordates and elongate vertebrates.

Science.gov (United States)

Miyashita, Tetsuto; Palmer, A Richard

2014-04-01

Hagfish represent an ancient lineage of boneless and jawless vertebrates. Among several curious behaviors they exhibit, solitary individuals in one dominant genus of hagfish (Eptatretus spp.) regularly rest in a tightly coiled posture. We present the first systematic treatment of this distinctive behavior. Individual northeastern Pacific hagfish (E. stoutii) exhibited significant handedness (preferred orientation of coiling). However, right-coiling and left-coiling individuals were equally common in the population. Individual hagfish likely develop a preference for one direction by repeating the preceding coiling direction. We also revisit classical accounts of chordate natural history and compare the coiling behavior of Eptatretus with other handed or lateralized behaviors in non-vertebrate chordates, lampreys, and derived vertebrates with elongate bodies. Handed behaviors occur in many of these groups, but they likely evolved independently. In contrast to vertebrates, morphological asymmetries may bias lateralized larval behaviors toward one side in cephalochordates and tunicates. As a consequence, no known handed behavior can be inferred to have existed in the common ancestor of vertebrates.

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

Caudal lumbar vertebral fractures in California Quarter Horse and Thoroughbred racehorses.

Science.gov (United States)

Collar, E M; Zavodovskaya, R; Spriet, M; Hitchens, P L; Wisner, T; Uzal, F A; Stover, S M

2015-09-01

To gain insight into the pathophysiology of equine lumbar vertebral fractures in racehorses. To characterise equine lumbar vertebral fractures in California racehorses. Retrospective case series and prospective case-control study. Racehorse post mortem reports and jockey injury reports were retrospectively reviewed. Vertebral specimens from 6 racehorses affected with lumbar vertebral fractures and 4 control racehorses subjected to euthanasia for nonspinal fracture were assessed using visual, radiographic, computed tomography and histological examinations. Lumbar vertebral fractures occurred in 38 Quarter Horse and 29 Thoroughbred racehorses over a 22 year period, primarily involving the 5th and/or 6th lumbar vertebrae (L5-L6; 87% of Quarter Horses and 48% of Thoroughbreds). Lumbar vertebral fractures were the third most common musculoskeletal cause of death in Quarter Horses and frequently involved a jockey injury. Lumbar vertebral specimens contained anatomical variations in the number of vertebrae, dorsal spinous processes and intertransverse articulations. Lumbar vertebral fractures examined in 6 racehorse specimens (5 Quarter Horses and one Thoroughbred) coursed obliquely in a cranioventral to caudodorsal direction across the adjacent L5-L6 vertebral endplates and intervertebral disc, although one case involved only one endplate. All cases had evidence of abnormalities on the ventral aspect of the vertebral bodies consistent with pre-existing, maladaptive pathology. Lumbar vertebral fractures occur in racehorses with pre-existing pathology at the L5-L6 vertebral junction that is likely predisposes horses to catastrophic fracture. Knowledge of these findings should encourage assessment of the lumbar vertebrae, therefore increasing detection of mild vertebral injuries and preventing catastrophic racehorse and associated jockey injuries. © 2014 EVJ Ltd.

Reintroduction of locally extinct vertebrates impacts arid soil fungal communities.

Science.gov (United States)

Clarke, Laurence J; Weyrich, Laura S; Cooper, Alan

2015-06-01

Introduced species have contributed to extinction of native vertebrates in many parts of the world. Changes to vertebrate assemblages are also likely to alter microbial communities through coextinction of some taxa and the introduction of others. Many attempts to restore degraded habitats involve removal of exotic vertebrates (livestock and feral animals) and reintroduction of locally extinct species, but the impact of such reintroductions on microbial communities is largely unknown. We used high-throughput DNA sequencing of the fungal internal transcribed spacer I (ITS1) region to examine whether replacing exotic vertebrates with reintroduced native vertebrates led to changes in soil fungal communities at a reserve in arid central Australia. Soil fungal diversity was significantly different between dune and swale (interdune) habitats. Fungal communities also differed significantly between sites with exotic or reintroduced native vertebrates after controlling for the effect of habitat. Several fungal operational taxonomic units (OTUs) found exclusively inside the reserve were present in scats from reintroduced native vertebrates, providing a direct link between the vertebrate assemblage and soil microbial communities. Our results show that changes to vertebrate assemblages through local extinctions and the invasion of exotic species can alter soil fungal communities. If local extinction of one or several species results in the coextinction of microbial taxa, the full complement of ecological interactions may never be restored. © 2015 John Wiley & Sons Ltd.

Balloon kyphoplasty for aged osteoporotic vertebral compressive fractures using domestic instruments

International Nuclear Information System (INIS)

Sun Gang; Jin Peng; Yi Yuhai; Xie Zhiyong; Zhang Xuping; Zhang Kangli

2006-01-01

Objective: To evaluate the efficacy and safety of balloon kyphoplasty in the treatment of painful osteoporosis vertebral compressive fractures using instruments made in China. Methods: 10 cases of painful osteoporotic vertebral compressive fractures, involved 11 vertebrae. Under X-ray fluoroscopy monitoring, the inflatable balloon were inserted into the fractured vertebral body via transpedicular route bilaterally. The balloon was inflated with injected contrast agent to restore vertebral height and form a cavity within vertebral body. The cavity was then filled with bone cement in toothpaste state period. The postoperative symptoms and the radiographic findings of vertebral height recovery were observed. Results: Balloon kyphoplasty was successful in all 10 cases with dramatic pain relief within 48 hours after the procedure without clinical complications. The height restoration of vertebral body was satisfactory with correction of kyphosis up to 6 degree-24 degree. Leakage of a small quantity of bone cement occurred at only the anterior border of the vertebral body. Conclusions: Kyphoplasty using domestic instruments for painful osteoporotic vertebral compressive fractures was effective and safe. (authors)

Vertebrate richness and biogeography in the Big Thicket of Texas

Science.gov (United States)

Michael H MacRoberts; Barbara R. MacRoberts; D. Craig Rudolph

2010-01-01

The Big Thicket of Texas has been described as rich in species and a “crossroads:” a place where organisms from many different regions meet. We examine the species richness and regional affiliations of Big Thicket vertebrates. We found that the Big Thicket is neither exceptionally rich in vertebrates nor is it a crossroads for vertebrates. Its vertebrate fauna is...

Imperfect isolation: factors and filters shaping Madagascar's extant vertebrate fauna.

Science.gov (United States)

Samonds, Karen E; Godfrey, Laurie R; Ali, Jason R; Goodman, Steven M; Vences, Miguel; Sutherland, Michael R; Irwin, Mitchell T; Krause, David W

2013-01-01

Analyses of phylogenetic topology and estimates of divergence timing have facilitated a reconstruction of Madagascar's colonization events by vertebrate animals, but that information alone does not reveal the major factors shaping the island's biogeographic history. Here, we examine profiles of Malagasy vertebrate clades through time within the context of the island's paleogeographical evolution to determine how particular events influenced the arrival of the island's extant groups. First we compare vertebrate profiles on Madagascar before and after selected events; then we compare tetrapod profiles on Madagascar to contemporary tetrapod compositions globally. We show that changes from the Mesozoic to the Cenozoic in the proportions of Madagascar's tetrapod clades (particularly its increase in the representation of birds and mammals) are tied to changes in their relative proportions elsewhere on the globe. Differences in the representation of vertebrate classes from the Mesozoic to the Cenozoic reflect the effects of extinction (i.e., the non-random susceptibility of the different vertebrate clades to purported catastrophic global events 65 million years ago), and new evolutionary opportunities for a subset of vertebrates with the relatively high potential for transoceanic dispersal potential. In comparison, changes in vertebrate class representation during the Cenozoic are minor. Despite the fact that the island's isolation has resulted in high vertebrate endemism and a unique and taxonomically imbalanced extant vertebrate assemblage (both hailed as testimony to its long isolation), that isolation was never complete. Indeed, Madagascar's extant tetrapod fauna owes more to colonization during the Cenozoic than to earlier arrivals. Madagascar's unusual vertebrate assemblage needs to be understood with reference to the basal character of clades originating prior to the K-T extinction, as well as to the differential transoceanic dispersal advantage of other, more

A unified anatomy ontology of the vertebrate skeletal system.

Directory of Open Access Journals (Sweden)

Wasila M Dahdul

Full Text Available The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO, to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish and multispecies (teleost, amphibian vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages, and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO, Gene Ontology (GO, Uberon, and Cell Ontology (CL, and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity.

A unified anatomy ontology of the vertebrate skeletal system.

Science.gov (United States)

Dahdul, Wasila M; Balhoff, James P; Blackburn, David C; Diehl, Alexander D; Haendel, Melissa A; Hall, Brian K; Lapp, Hilmar; Lundberg, John G; Mungall, Christopher J; Ringwald, Martin; Segerdell, Erik; Van Slyke, Ceri E; Vickaryous, Matthew K; Westerfield, Monte; Mabee, Paula M

2012-01-01

The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO), to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish) and multispecies (teleost, amphibian) vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages), and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO), Gene Ontology (GO), Uberon, and Cell Ontology (CL), and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity.

A Unified Anatomy Ontology of the Vertebrate Skeletal System

Science.gov (United States)

Dahdul, Wasila M.; Balhoff, James P.; Blackburn, David C.; Diehl, Alexander D.; Haendel, Melissa A.; Hall, Brian K.; Lapp, Hilmar; Lundberg, John G.; Mungall, Christopher J.; Ringwald, Martin; Segerdell, Erik; Van Slyke, Ceri E.; Vickaryous, Matthew K.; Westerfield, Monte; Mabee, Paula M.

2012-01-01

The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO), to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish) and multispecies (teleost, amphibian) vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages), and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO), Gene Ontology (GO), Uberon, and Cell Ontology (CL), and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity. PMID:23251424

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.

50 CFR 17.84 - Special rules-vertebrates.

Science.gov (United States)

2010-10-01

... 50 Wildlife and Fisheries 2 2010-10-01 2010-10-01 false Special rules-vertebrates. 17.84 Section 17.84 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR....84 Special rules—vertebrates. (a) Delmarva Peninsula fox squirrel (Sciurus niger cinereus). (1) The...

Vertebral column regionalisation in Chinook salmon, Oncorhynchus tshawytscha.

Science.gov (United States)

De Clercq, A; Perrott, M R; Davie, P S; Preece, M A; Wybourne, B; Ruff, N; Huysseune, A; Witten, P E

2017-10-01

Teleost vertebral centra are often similar in size and shape, but vertebral-associated elements, i.e. neural arches, haemal arches and ribs, show regional differences. Here we examine how the presence, absence and specific anatomical and histological characters of vertebral centra-associated elements can be used to define vertebral column regions in juvenile Chinook salmon (Oncorhynchus tshawytscha). To investigate if the presence of regions within the vertebral column is independent of temperature, animals raised at 8 and 12 °C were studied at 1400 and 1530 degreedays, in the freshwater phase of the life cycle. Anatomy and composition of the skeletal tissues of the vertebral column were analysed using Alizarin red S whole-mount staining and histological sections. Six regions, termed I-VI, are recognised in the vertebral column of specimens of both temperature groups. Postcranial vertebrae (region I) carry neural arches and parapophyses but lack ribs. Abdominal vertebrae (region II) carry neural arches and ribs that articulate with parapophyses. Elastic- and fibrohyaline cartilage and Sharpey's fibres connect the bone of the parapophyses to the bone of the ribs. In the transitional region (III) vertebrae carry neural arches and parapophyses change stepwise into haemal arches. Ribs decrease in size, anterior to posterior. Vestigial ribs remain attached to the haemal arches with Sharpey's fibres. Caudal vertebrae (region IV) carry neural and haemal arches and spines. Basidorsals and basiventrals are small and surrounded by cancellous bone. Preural vertebrae (region V) carry neural and haemal arches with modified neural and haemal spines to support the caudal fin. Ural vertebrae (region VI) carry hypurals and epurals that represent modified haemal and neural arches and spines, respectively. The postcranial and transitional vertebrae and their respective characters are usually recognised, but should be considered as regions within the vertebral column of teleosts

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.

Transoral vertebral augmentation with polymethylmethacrylate in the treatment of a patient with a dens fracture nonunion and subarticular vertebral body fracture of C2

International Nuclear Information System (INIS)

Beall, Douglas P.; Martin, Hal D.; Stapp, Annette M.; Stanfield, Matthew

2007-01-01

The injection of polymethylmethacrylate (PMMA) is a minimally invasive, image-guided procedure used to treat vertebral fractures due to osteoporosis, metastatic lesions, multiple myeloma, and benign but destabilizing bone tumors. The injection of PMMA into the C2 vertebral body using the transoral technique has been reported in three separate patients for treatment of benign tumors (a vertebral hemangioma and an aneurysmal bone cyst) and for multiple myeloma in the third patient. Although the injection of PMMA into the vertebral body is most commonly performed to treat benign vertebral compression fractures, a transoral C2 approach has not been reported in the English literature as a treatment for a benign fracture of C2. We report the treatment of a fracture and nonunion of the base of the dens and a subarticular fracture of the vertebral body of C2 using a bilateral transoral approach. (orig.)

Vertebral Fractures After Discontinuation of Denosumab

DEFF Research Database (Denmark)

Cummings, Steven R; Ferrari, Serge; Eastell, Richard

2018-01-01

. We analyzed the risk of new or worsening vertebral fractures, especially multiple vertebral fractures, in participants who discontinued denosumab during the FREEDOM study or its Extension. Participants received ≥2 doses of denosumab or placebo Q6M, discontinued treatment, and stayed in the study ≥7...... months after the last dose. Of 1001 participants who discontinued denosumab during FREEDOM or Extension, the vertebral fracture rate increased from 1.2 per 100 participant-years during the on-treatment period to 7.1, similar to participants who received and then discontinued placebo (n = 470; 8.5 per 100....... Therefore, patients who discontinue denosumab should rapidly transition to an alternative antiresorptive treatment. Clinicaltrails.gov: NCT00089791 (FREEDOM) and NCT00523341 (Extension). © 2017 American Society for Bone and Mineral Research....

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.

The characteristic of rBMD distribution in lumbar vertebral body

International Nuclear Information System (INIS)

Wang Chenguang; Xiao Xiangsheng; Chen Xingrong; Shen Tianzhen; Liu Guanghua; Hong Qingjian; Ji Rongming; Zhou Weiming

1998-01-01

Purpose: To determine the distribution and variation of rBMD in human lumbar vertebral body. Methods: The BMD and rBMD of 28 samples of lumbar body were measured with QCT. The rBMD was measured in the regions of anterior, anterolateral, posterolateral and central, superior-level, middle-level and inferior-level of the vertebral bodies. The relationship between BMD and rBMD were statistically analysed with multiple regression. Results: The rBMD of the inferior vertebral body was higher than that of the superior and middle portions (P<0.05); the central and posterolateral higher than the anterior and anterolateral (P<0.05). The rBMD of posterioinferior vertebral body was the highest. The multiple regression showed that the standard partial regression coefficient of inferior was larger than the superior and middle; the anterior and central were larger than the other regions of the vertebra. Variations of the BMD of vertebral body were mostly related to the rBMD of anterior and central parts. Conclusion: The distribution of BMD are heterogeneous in vertebral body. The anterior and central part of vertebral body are most sensitive to bone loss in osteoporosis. It is emphasized that the rBMD of anterior and central part of vertebral body should be measured for following the osteoporosis

Differential preservation of vertebrates in Southeast Asian caves

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Julien Louys

2017-09-01

Full Text Available Caves have been an important source of vertebrate fossils for much of Southeast Asia, particularly for the Quaternary. Despite this importance, the mechanisms by which vertebrate remains accumulate and preserve in Southeast Asian caves has never been systematically reviewed or examined. Here, we present the results of three years of cave surveys in Indonesia and Timor-Leste, describing cave systems and their attendant vertebrate accumulations in diverse geological, biogeographical, and environmental settings. While each cave system is unique, we find that the accumulation and preservation of vertebrate remains are highly dependent on local geology and environment. These factors notwithstanding, we find the dominant factor responsible for faunal deposition is the presence or absence of biological accumulating agents, a factor directly dictated by biogeographical history. In small, isolated, volcanic islands, the only significant accumulation occurs in archaeological settings, thereby limiting our understanding of the palaeontology of those islands prior to human arrival. In karstic landscapes on both oceanic and continental islands, our understanding of the long-term preservation of vertebrates is still in its infancy. The formation processes of vertebrate-bearing breccias, their taphonomic histories, and the criteria used to determine whether these represent syngenetic or multiple deposits remain critically understudied. The latter in particular has important implications for arguments on how breccia deposits from the region should be analysed and interpreted when reconstructing palaeoenvironments.

Vertebral deformity arising from an accelerated "creep" mechanism.

Science.gov (United States)

Luo, Jin; Pollintine, Phillip; Gomm, Edward; Dolan, Patricia; Adams, Michael A

2012-09-01

Vertebral deformities often occur in patients who recall no trauma, and display no evident fracture on radiographs. We hypothesise that vertebral deformity can occur by a gradual creep mechanism which is accelerated following minor damage. "Creep" is continuous deformation under constant load. Forty-five thoracolumbar spine motion segments were tested from cadavers aged 42-92 years. Vertebral body areal BMD was measured using DXA. Specimens were compressed at 1 kN for 30 min, while creep in each vertebral body was measured using an optical MacReflex system. After 30 min recovery, each specimen was subjected to a controlled overload event which caused minor damage to one of its vertebrae. The creep test was then repeated. Vertebral body creep was measurable in specimens with BMD Creep was greater anteriorly than posteriorly (p creep by 800 % (anteriorly), 1,000 % (centrally) and 600 % (posteriorly). In 34 vertebrae with complete before-and-after data, anterior wedging occurring during the 1st creep test averaged 0.07° (STD 0.17°), and in the 2nd test (after minor damage) it averaged 0.79° (STD 1.03°). The increase was highly significant (P creep test was proportional to the severity of damage, as quantified by specimen height loss during the overload event (r (2) = 0.51, p creep to such an extent that it makes a substantial contribution to vertebral deformity.

Worldwide prevalence and incidence of osteoporotic vertebral fractures.

Science.gov (United States)

Ballane, G; Cauley, J A; Luckey, M M; El-Hajj Fuleihan, G

2017-05-01

We investigated the prevalence and incidence of vertebral fractures worldwide. We used a systematic Medline search current to 2015 and updated as per authors' libraries. A total of 62 articles of fair to good quality and comparable methods for vertebral fracture identification were considered. The prevalence of morphometric vertebral fractures in European women is highest in Scandinavia (26%) and lowest in Eastern Europe (18%). Prevalence rates in North America (NA) for White women ≥50 are 20-24%, with a White/Black ratio of 1.6. Rates in women ≥50 years in Latin America are overall lower than Europe and NA (11-19%). In Asia, rates in women above ≥65 are highest in Japan (24%), lowest in Indonesia (9%), and in the Middle East, Lebanon, rates are 20%. The highest-lowest ratio between countries, within and across continents, varied from 1.4-2.6. Incidence data is less abundant and more heterogeneous. Age-standardized rates in studies combining hospitalized and ambulatory vertebral fractures are highest in South Korea, USA, and Hong Kong and lowest in the UK. Neither a North-South gradient nor a relation to urbanization is evident. Conversely, the incidence of hospitalized vertebral fractures in European patients ≥50 shows a North-South gradient with 3-3.7-fold variability. In the USA, rates in Whites are approximately 4-fold higher than in Blacks. Vertebral fractures variation worldwide is lower than observed with hip fractures, and some of highest rates are unexpectedly from Asia. Better quality representative studies are needed. We investigate the occurrence of vertebral fractures, worldwide, using published data current until the present. Worldwide, the variation in vertebral fractures is lower than observed for hip fractures. Some of the highest rates are from North America and unexpectedly Asia. The highest-lowest ratio between countries, within and across continents, varied from 1.4-2.6. Better quality representative data is needed.

Clinical application of multislice spiral CT angiography in evaluation of anomalous vertebral artery

International Nuclear Information System (INIS)

Hua Rui; Liu Jun; Zhang Yu

2008-01-01

Objective: To evaluate the diagnostic value of 16-slice spiral computed tomography angiography (MSCTA) in evaluation of anomalous vertebral artery. Methods: MSCTA data from 32 patients with anomalous vertebral artery were retrospectively analyzed. Results: 22 cases had vertebral artery course variation (bended into the C 5 , C 4 or C 3 foramen transversarium), 7 cases had variation in the prevertebral segments of vertebral arteries, 15 patients had unilateral vertebral congenital stenosis, 1 case had double vertebral artery branch, 1 case had vertebral arterial fenestration, and 2 cases had vertebral artery in one side that did not converged upon basilar artery and unilateral vertebral artery formed basilar artery. Conclusion: MSCTA is a useful noninvasive imaging tool for the diagnosis of vertebral artery variations. (authors)

Clinical and radiological evaluation in vertebral artery dissections

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Murat Çabalar

2013-04-01

Full Text Available In recent years, vertebral artery dissection (VAD is reported more frequently as a cause of young cerebrovascular accidents. It can occur spontaneously or following a neck manipulation and trauma. The patients were 3 females (mean age: 35±26 years and 7 males (mean age: 37.71±4.96 years. Only 2 patients described neck trauma. Cerebellar findings were prominent in all cases. On radiological investigation, vascular changes of vertebral arteries were detected bilaterally in 2 cases, right in 5 and left in 3 cases. All the cases were treated with anticoagulant therapy and cured but 1 with sequela. Prognosis of vertebral artery dissection is generally good by early diagnosis and treatment. In this article, we reported clinical and radiological properties of 10 vertebral artery dissection cases.

An invertebrate stomach's view on vertebrate ecology: certain invertebrates could be used as "vertebrate samplers" and deliver DNA-based information on many aspects of vertebrate ecology.

Science.gov (United States)

Calvignac-Spencer, Sébastien; Leendertz, Fabian H; Gilbert, M Thomas P; Schubert, Grit

2013-11-01

Recent studies suggest that vertebrate genetic material ingested by invertebrates (iDNA) can be used to investigate vertebrate ecology. Given the ubiquity of invertebrates that feed on vertebrates across the globe, iDNA might qualify as a very powerful tool for 21st century population and conservation biologists. Here, we identify some invertebrate characteristics that will likely influence iDNA retrieval and elaborate on the potential uses of invertebrate-derived information. We hypothesize that beyond inventorying local faunal diversity, iDNA should allow for more profound insights into wildlife population density, size, mortality, and infectious agents. Based on the similarities of iDNA with other low-quality sources of DNA, a general technical framework for iDNA analyses is proposed. As it is likely that no such thing as a single ideal iDNA sampler exists, forthcoming research efforts should aim at cataloguing invertebrate properties relevant to iDNA retrieval so as to guide future usage of the invertebrate tool box. © 2013 WILEY Periodicals, Inc.

Use of cervical vertebral dimensions for assessment of children growth.

Science.gov (United States)

Caldas, Maria de Paula; Ambrosano, Gláucia Maria Bovi; Haiter-Neto, Francisco

2007-04-01

The purpose of this study was to investigate whether skeletal maturation using cephalometric radiographs could be used in a Brazilian population. The study population was selected from the files of the Oral Radiological Clinic of the Dental School of Piracicaba, Brazil and consisted of 128 girls and 110 boys (7.0 to 15.9 years old) who had cephalometric and hand-wrist radiographs taken on the same day. Cervical vertebral bone age was evaluated using the method described by Mito and colleagues in 2002. Bone age was assessed by the Tanner-Whitehouse (TW3) method and was used as a gold standard to determine the reliability of cervical vertebral bone age. An analysis of variance and Tukey's post-hoc test were used to compare cervical vertebral bone age, bone age and chronological age at 5% significance level. The analysis of the Brazilian female children data showed that there was a statistically significant difference (pcervical vertebral bone age and chronological age and between bone age and chronological age. However no statistically significant difference (p>0.05) was found between cervical vertebral bone age and bone age. Differently, the analysis of the male children data revealed a statistically significant difference (pcervical vertebral bone age and bone age and between cervical vertebral bone age and chronological age (pmaturation on cephalometric radiographs by determination of vertebral bone age can be applied to Brazilian females only. The development of a new method to objectively evaluate cervical vertebral bone age in males is needed.

The origin of vertebrate limbs.

Science.gov (United States)

Coates, M I

1994-01-01

The earliest tetrapod limbs are polydactylous, morphologically varied and do not conform to an archetypal pattern. These discoveries, combined with the unravelling of limb developmental morphogenetic and regulatory mechanisms, have prompted a re-examination of vertebrate limb evolution. The rich fossil record of vertebrate fins/limbs, although restricted to skeletal tissues, exceeds the morphological diversity of the extant biota, and a systematic approach to limb evolution produces an informative picture of evolutionary change. A composite framework of several phylogenetic hypotheses is presented incorporating living and fossil taxa, including the first report of an acanthodian metapterygium and a new reconstruction of the axial skeleton and caudal fin of Acanthostega gunnari. Although significant nodes in vertebrate phylogeny remain poorly resolved, clear patterns of morphogenetic evolution emerge: median fin origination and elaboration initially precedes that of paired fins; pectoral fins initially precede pelvic fin development; evolving patterns of fin distribution, skeletal tissue diversity and structural complexity become decoupled with increased taxonomic divergence. Transformational sequences apparent from the fish-tetrapod transition are reiterated among extant lungfishes, indicating further directions for comparative experimental research. The evolutionary diversification of vertebrate fin and limb patterns challenges a simple linkage between Hox gene conservation, expression and morphology. A phylogenetic framework is necessary in order to distinguish shared from derived characters in experimental model regulatory systems. Hox and related genomic evolution may include convergent patterns underlying functional and morphological diversification. Brachydanio is suggested as an example where tail-drive patterning demands may have converged with the regulation of highly differentiated limbs in tetrapods.

Preoperative MRI evaluation of vertebral hemangiomas treated with percutaneous vertebroplasty

International Nuclear Information System (INIS)

Liu Xiaoping; Wu Chungen; Li Minghua; Li Yuehua; Gu Yifeng; Cheng Yongde

2012-01-01

Objective: To discuss the clinical value of preoperative magnetic resonance imaging examination in guiding the treatment of vertebral hemangiomas with percutaneous vertebroplasty (PVP). Methods: A total of 286 patients with vertebral hemangiomas detected on spine MRI in authors' Department were enrolled in this study. The patient's age, the lesion's size and location, the clinical symptoms, MRI findings, etc. were retrospectively analyzed. Results: A total of 336 vertebral bodies were affected in 286 patients. The lesions were mainly located at the lumbar spine (43.15%) and the thoracic spine (37.80%). The highest incidence of disease was seen in 50-59 years old patients (34.62%). The mean diameter of the lesions was 14.56 mm. Solitary lesion was seen in 85.66% of patients, while two vertebral bodies involved were seen in 10.14% of patients. Twelve cases (4.20%) simply presented as back pain at the related vertebral bodies. Two patients showed signs due to spinal cord compression. All aggressive vertebral hemangiomas were manifested as iso-lower signal on T1-weighted images and higher signal on T2-weighted images. Simple PVP was performed in 4 cases, and subtotal tumor excision together with PVP was carried out in two patients with aggressive vertebral hemangiomas. Conclusion: Evaluation of vertebral hemangiomas with MRI performed prior to percutaneous vertebroplasty is very helpful in guiding the selection of therapeutic scheme. (authors)

Multiple chromosomal rearrangements structured the ancestral vertebrate Hox-bearing protochromosomes.

Directory of Open Access Journals (Sweden)

Vincent J Lynch

2009-01-01

Full Text Available While the proposal that large-scale genome expansions occurred early in vertebrate evolution is widely accepted, the exact mechanisms of the expansion--such as a single or multiple rounds of whole genome duplication, bloc chromosome duplications, large-scale individual gene duplications, or some combination of these--is unclear. Gene families with a single invertebrate member but four vertebrate members, such as the Hox clusters, provided early support for Ohno's hypothesis that two rounds of genome duplication (the 2R-model occurred in the stem lineage of extant vertebrates. However, despite extensive study, the duplication history of the Hox clusters has remained unclear, calling into question its usefulness in resolving the role of large-scale gene or genome duplications in early vertebrates. Here, we present a phylogenetic analysis of the vertebrate Hox clusters and several linked genes (the Hox "paralogon" and show that different phylogenies are obtained for Dlx and Col genes than for Hox and ErbB genes. We show that these results are robust to errors in phylogenetic inference and suggest that these competing phylogenies can be resolved if two chromosomal crossover events occurred in the ancestral vertebrate. These results resolve conflicting data on the order of Hox gene duplications and the role of genome duplication in vertebrate evolution and suggest that a period of genome reorganization occurred after genome duplications in early vertebrates.

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...

MRI-based anatomical landmarks for the identification of thoracic vertebral levels

International Nuclear Information System (INIS)

Connor, S.E.J.; Shah, A.; Latifoltojar, H.; Lung, P.

2013-01-01

Aim: To identify soft-tissue and bony anatomical landmarks on dedicated thoracic spine magnetic resonance imaging (MRI), and to assess their detectability, reproducibility, and accuracy in predicting specific thoracic vertebral levels. Materials and methods: One hundred dedicated thoracic MRI studies were retrospectively analysed by two radiologists independently. Ten bone and soft-tissue landmarks were localized to the adjacent vertebral level. The true numerical thoracic vertebral level was subsequently determined and recorded by cross referencing with a sagittal cervico-thoracic “counting scan”. Results: Six landmarks were defined in ≥98% cases; however, there was a low interobserver percentage agreement for the defined vertebral levels (>70% for only one landmark). The most useful landmark for defining a specific vertebral level was the most superior rib (98% detection, 95% interobserver agreement, 98% at a single vertebral level, 0.07 SD). Eight landmarks localized to a specific thoracic segment in only 16–44% of cases, with a standard deviation of >0.5 vertebral levels and with a range which was greater than four vertebral levels. Conclusion: The C2 vertebra must be identified and cross referenced to the dedicated thoracic spine MRI, as other MRI-based anatomical landmarks are unreliable in determining the correct thoracic vertebral level

Molecular Mechanism of Somite Development

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Gulfidan Coskun

2013-06-01

Full Text Available From third week of gestation, notochord and the neural folds begin to gather at the center of the embryo to form the paraxial mesoderm. Paraxial mesoderm separates into blocks of cells called somitomers at the lateral sides of the neural tube of the head region. At the beginning of the third week somitomeres take ring shapes and form blocks of somites from occipital region to caudal region. Although somites are transient structures, they are extremely important in organizing the segmental pattern of vertebrate embryos. Somites give rise to the cells that form the vertebrae and ribs, the dermis of the dorsal skin, the skeletal muscles of the back, and the skeletal muscles of the body wall and limbs. Somitogenesis are formed by a genetic mechanism that is regulated by cyclical expression of genes in the Notch, Wnt and fibroblast growth factor signaling pathways. The prevailing model of the mechanism governing somitogenesis is the “clock and wave front”. Somitogenesis has components of periodicity, separation, epithelialization and axial specification. According to this model, the clock causes cells to undergo repeated oscillations, with a particular phase of each oscillation defining the competency of cells in the presomitic mesoderm to form a somite. Any disruption in this mechanism can be cause of severe segmentation defects of the vertebrae and congenital anomalies. In this review, we discuss the molecular mechanisms underlying the somitogenesis which is an important part of morphogenesis. [Archives Medical Review Journal 2013; 22(3.000: 362-376

Vascular complications of prosthetic inter-vertebral discs.

Science.gov (United States)

Daly, Kevin J; Ross, E Raymond S; Norris, Heather; McCollum, Charles N

2006-10-01

Five consecutive cases of prosthetic inter-vertebral disc displacement with severe vascular complications on revisional surgery are described. The objective of this case report is to warn spinal surgeons that major vascular complications are likely with anterior displacement of inter-vertebral discs. We have not been able to find a previous report on vascular complications associated with anterior displacement of prosthetic inter-vertebral discs. In all five patients the prosthetic disc had eroded into the bifurcation of the inferior vena cava and the left common iliac vein. In three cases the aortic bifurcation was also involved. The fibrosis was so severe that dissecting out the arteries and veins to provide access to the relevant disc proved impossible. Formal division of the left common iliac vein and artery with subsequent repair was our solution. Anterior inter-vertebral disc displacement was associated with severe vascular injury. Preventing anterior disc displacement is essential in disc design. In the event of anterior displacement, disc removal should be planned with a Vascular Surgeon.

Evolution of the vertebrate phototransduction cascade activation steps.

Science.gov (United States)

Lamb, Trevor D; Hunt, David M

2017-11-01

We examine the molecular phylogeny of the proteins underlying the activation steps of vertebrate phototransduction, for both agnathan and jawed vertebrate taxa. We expand the number of taxa analysed and we update the alignment and tree building methodology from a previous analysis. For each of the four primary components (the G-protein transducin alpha subunit, Gα T , the cyclic GMP phosphodiesterase, PDE6, and the alpha and beta subunits of the cGMP-gated ion channel, CNGC), the phylogenies appear consistent with expansion from an ancestral proto-vertebrate cascade during two rounds of whole-genome duplication followed by divergence of the agnathan and jawed vertebrate lineages. In each case, we consider possible scenarios for the underlying gene duplications and losses, and we apply relevant constraints to the tree construction. From tests of the topology of the resulting trees, we obtain a scenario for the expansion of each component during 2R that accurately fits the observations. Similar analysis of the visual opsins indicates that the only expansion to have occurred during 2R was the formation of Rh1 and Rh2. Finally, we propose a hypothetical scenario for the conversion of an ancestral chordate cascade into the proto-vertebrate phototransduction cascade, prior to whole-genome duplication. Together, our models provide a plausible account for the origin and expansion of the vertebrate phototransduction cascade. Copyright © 2017 Elsevier Inc. All rights reserved.

iDNA screening: Disease vectors as vertebrate samplers.

Science.gov (United States)

Kocher, Arthur; de Thoisy, Benoit; Catzeflis, François; Valière, Sophie; Bañuls, Anne-Laure; Murienne, Jérôme

2017-11-01

In the current context of global change and human-induced biodiversity decline, there is an urgent need for developing sampling approaches able to accurately describe the state of biodiversity. Traditional surveys of vertebrate fauna involve time-consuming and skill-demanding field methods. Recently, the use of DNA derived from invertebrate parasites (leeches and blowflies) was suggested as a new tool for vertebrate diversity assessment. Bloodmeal analyses of arthropod disease vectors have long been performed to describe their feeding behaviour, for epidemiological purposes. On the other hand, this existing expertise has not yet been applied to investigate vertebrate fauna per se. Here, we evaluate the usefulness of hematophagous dipterans as vertebrate samplers. Blood-fed sand flies and mosquitoes were collected in Amazonian forest sites and analysed using high-throughput sequencing of short mitochondrial markers. Bloodmeal identifications highlighted contrasting ecological features and feeding behaviour among dipteran species, which allowed unveiling arboreal and terrestrial mammals of various body size, as well as birds, lizards and amphibians. Additionally, lower vertebrate diversity was found in sites undergoing higher levels of human-induced perturbation. These results suggest that, in addition to providing precious information on disease vector host use, dipteran bloodmeal analyses may represent a useful tool in the study of vertebrate communities. Although further effort is required to validate the approach and consider its application to large-scale studies, this first work opens up promising perspectives for biodiversity monitoring and eco-epidemiology. © 2017 John Wiley & Sons Ltd.

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.

Evolution of vertebrate sex chromosomes and dosage compensation.

Science.gov (United States)

Graves, Jennifer A Marshall

2016-01-01

Differentiated sex chromosomes in mammals and other vertebrates evolved independently but in strikingly similar ways. Vertebrates with differentiated sex chromosomes share the problems of the unequal expression of the genes borne on sex chromosomes, both between the sexes and with respect to autosomes. Dosage compensation of genes on sex chromosomes is surprisingly variable - and can even be absent - in different vertebrate groups. Systems that compensate for different gene dosages include a wide range of global, regional and gene-by-gene processes that differ in their extent and their molecular mechanisms. However, many elements of these control systems are similar across distant phylogenetic divisions and show parallels to other gene silencing systems. These dosage systems cannot be identical by descent but were probably constructed from elements of ancient silencing mechanisms that are ubiquitous among vertebrates and shared throughout eukaryotes.

Distal vertebral artery reconstruction when managing vertebrobasilar insufficiency

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D. M. Galaktionov

2017-11-01

Full Text Available This article presents a literature review devoted to the reconstruction of the distal vertebral artery and a clinical case of successful surgical treatment of a patient suffering from vertebrobasilar insufficiency caused by occlusion of the vertebral artery in a proximal segment. The external carotid artery-distal vertebral artery bypass was performed by using the radial artery.Received 27 February 2017. Revised 25 July 2017. Accepted 3 August 2017.Funding: The study did not have sponsorship.Conflict of interest: The authors declare no conflict of interest. 

Ancient duplications and functional divergence in the interferon regulatory factors of vertebrates provide insights into the evolution of vertebrate immune systems.

Science.gov (United States)

Du, Kang; Zhong, Zaixuan; Fang, Chengchi; Dai, Wei; Shen, Yanjun; Gan, Xiaoni; He, Shunping

2018-04-01

Interferon regulatory factors (IRFs) were first discovered as transcription factors that regulate the transcription of human interferon (IFN)-β. Increasing evidence shows that they might be important players involved in Adaptive immune system (AIS) evolution. Although numbers of IRFs have been identified in chordates, the evolutionary history and functional diversity of this gene family during the early evolution of vertebrates have remained obscure. Using IRF HMM profile and HMMER searches, we identified 148 IRFs in 11 vertebrates and 4 protochordates. For them, we reconstructed the phylogenetic relationships, determined the synteny conservation, investigated the profile of natural selection, and analyzed the expression patterns in four "living fossil" vertebrates: lamprey, elephant shark, coelacanth and bichir. The results from phylogeny and synteny analysis imply that vertebrate IRFs evolved from three predecessors, instead of four as suggested in a previous study, as results from an ancient duplication followed by special expansions and lost during the vertebrate evolution. The profile of natural selection and expression reveals functional dynamics during the process. Together, they suggest that the 2nd whole-genome duplication (2WGD) provided raw materials for innovation in the IRF family, and that the birth of type-I IFN might be an important factor inducing the establishment of IRF-mediated immune networks. As a member involved in the AIS evolution, IRF provide insights into the process and mechanism involved in the complexity and novelties of vertebrate immune systems. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Combined endovascular and surgical treatment in vertebral arteriovenous fistula

International Nuclear Information System (INIS)

Nakstad, P.H.; Haakonsen, M.; Magnaes, B.; Hetland, S.

1997-01-01

A 7-year-old girl with a right-sided congenital arteriovenous fistula in the neck was admitted with signs of cardial incompensation. Her fistula was fed from the right vertebral artery in antegrade as well as retrograde directions. A steal from the intracranial arteries was established. In addition, smaller feeding arteries from the neck were found. She was operated on with ligation of the right vertebral artery proximal to the fistula but the attempted ligation of the artery cranially to the fistula was unsuccessful. She was therefore embolized by the formation of a plug of platinum fiber coils in the upper right vertebral artery. Catheterization was performed from the left vertebral artery via the basilar artery. Persisting minor feeders to the fistula from cervical arteries were embolized in a second session. Finally, surgical extirpation of the fistula was performed together with the operative ligation of a crossover feeding artery from the left vertebral artery. Her heart size, heart rate and blood pressure were successively normalized. (orig.)

Evolutionary growth process of highly conserved sequences in vertebrate genomes.

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Ishibashi, Minaka; Noda, Akiko Ogura; Sakate, Ryuichi; Imanishi, Tadashi

2012-08-01

Genome sequence comparison between evolutionarily distant species revealed ultraconserved elements (UCEs) among mammals under strong purifying selection. Most of them were also conserved among vertebrates. Because they tend to be located in the flanking regions of developmental genes, they would have fundamental roles in creating vertebrate body plans. However, the evolutionary origin and selection mechanism of these UCEs remain unclear. Here we report that UCEs arose in primitive vertebrates, and gradually grew in vertebrate evolution. We searched for UCEs in two teleost fishes, Tetraodon nigroviridis and Oryzias latipes, and found 554 UCEs with 100% identity over 100 bps. Comparison of teleost and mammalian UCEs revealed 43 pairs of common, jawed-vertebrate UCEs (jUCE) with high sequence identities, ranging from 83.1% to 99.2%. Ten of them retain lower similarities to the Petromyzon marinus genome, and the substitution rates of four non-exonic jUCEs were reduced after the teleost-mammal divergence, suggesting that robust conservation had been acquired in the jawed vertebrate lineage. Our results indicate that prototypical UCEs originated before the divergence of jawed and jawless vertebrates and have been frozen as perfect conserved sequences in the jawed vertebrate lineage. In addition, our comparative sequence analyses of UCEs and neighboring regions resulted in a discovery of lineage-specific conserved sequences. They were added progressively to prototypical UCEs, suggesting step-wise acquisition of novel regulatory roles. Our results indicate that conserved non-coding elements (CNEs) consist of blocks with distinct evolutionary history, each having been frozen since different evolutionary era along the vertebrate lineage. Copyright © 2012 Elsevier B.V. All rights reserved.

Microgravity simulation activates Cdc42 via Rap1GDS1 to promote vascular branch morphogenesis during vasculogenesis

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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.

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

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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.

Closure of the vertebral canal in human embryos and fetuses

NARCIS (Netherlands)

Mekonen, Hayelom K.; Hikspoors, Jill P. J. M.; Mommen, Greet; Kruepunga, Nutmethee; Köhler, S. Eleonore; Lamers, Wouter H.

2017-01-01

The vertebral column is the paradigm of the metameric architecture of the vertebrate body. Because the number of somites is a convenient parameter to stage early human embryos, we explored whether the closure of the vertebral canal could be used similarly for staging embryos between 7 and 10weeks of

Gout and the Risk of Non-vertebral Fracture.

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Kim, Seoyoung C; Paik, Julie M; Liu, Jun; Curhan, Gary C; Solomon, Daniel H

2017-02-01

Prior studies suggest an association between osteoporosis, systemic inflammation, and pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6. Conflicting findings exist on the association between hyperuricemia and osteoporosis. Furthermore, it remains unknown whether gout, a common inflammatory arthritis, affects fracture risk. Using data from a US commercial health plan (2004-2013), we evaluated the risk of non-vertebral fracture (ie, forearm, wrist, hip, and pelvis) in patients with gout versus those without. Gout patients were identified with ≥2 diagnosis codes and ≥1 dispensing for a gout-related drug. Non-gout patients, identified with ≥2 visits coded for any diagnosis and ≥1 dispensing for any prescription drugs, were free of gout diagnosis and received no gout-related drugs. Hip fracture was the secondary outcome. Fractures were identified with a combination of diagnosis and procedure codes. Cox proportional hazards models compared the risk of non-vertebral fracture in gout patients versus non-gout, adjusting for more than 40 risk factors for osteoporotic fracture. Among gout patients with baseline serum uric acid (sUA) measurements available, we assessed the risk of non-vertebral fracture associated with sUA. We identified 73,202 gout and 219,606 non-gout patients, matched on age, sex, and the date of study entry. The mean age was 60 years and 82% were men. Over the mean 2-year follow-up, the incidence rate of non-vertebral fracture per 1,000 person-years was 2.92 in gout and 2.66 in non-gout. The adjusted hazard ratio (HR) was 0.98 (95% confidence interval [CI] 0.85-1.12) for non-vertebral fracture and 0.83 (95% CI 0.65-1.07) for hip fracture in gout versus non-gout. Subgroup analysis (n = 15,079) showed no association between baseline sUA and non-vertebral fracture (HR = 1.03, 95% CI 0.93-1.15), adjusted for age, sex, comorbidity score, and number of any prescription drugs. Gout was not associated with a risk of non-vertebral

Built for speed: strain in the cartilaginous vertebral columns of sharks.

Science.gov (United States)

Porter, M E; Diaz, Candido; Sturm, Joshua J; Grotmol, Sindre; Summers, A P; Long, John H

2014-02-01

In most bony fishes vertebral column strain during locomotion is almost exclusively in the intervertebral joints, and when these joints move there is the potential to store and release strain energy. Since cartilaginous fishes have poorly mineralized vertebral centra, we tested whether the vertebral bodies undergo substantial strain and thus may be sites of energy storage during locomotion. We measured axial strains of the intervertebral joints and vertebrae in vivo and ex vivo to characterize the dynamic behavior of the vertebral column. We used sonomicrometry to directly measure in vivo and in situ strains of intervertebral joints and vertebrae of Squalus acanthias swimming in a flume. For ex vivo measurements, we used a materials testing system to dynamically bend segments of vertebral column at frequencies ranging from 0.25 to 1.00 Hz and a range of physiologically relevant curvatures, which were determined using a kinematic analysis. The vertebral centra of S. acanthias undergo strain during in vivo volitional movements as well as in situ passive movements. Moreover, when isolated segments of vertebral column were tested during mechanical bending, we measured the same magnitudes of strain. These data support our hypothesis that vertebral column strain in lateral bending is not limited to the intervertebral joints. In histological sections, we found that the vertebral column of S. acanthias has an intracentral canal that is open and covered with a velum layer. An open intracentral canal may indicate that the centra are acting as tunics around some sections of a hydrostat, effectively stiffening the vertebral column. These data suggest that the entire vertebral column of sharks, both joints and centra, is mechanically engaged as a dynamic spring during locomotion. Copyright © 2013 Elsevier GmbH. All rights reserved.

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

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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

TMEM45A Is Dispensable for Epidermal Morphogenesis, Keratinization and Barrier Formation.

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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.

Vertebral split fractures: Technical feasibility of percutaneous vertebroplasty

Energy Technology Data Exchange (ETDEWEB)

Huwart, Laurent, E-mail: huwart.laurent@wanadoo.fr [Department of Radiology, Hôpital Archet 2, Centre Hospitalo-Universitaire de Nice, Nice (France); Foti, Pauline, E-mail: pfoti@hotmail.fr [Department of Biostatistics, Hôpital Archet 2, Centre Hospitalo-Universitaire de Nice, Nice (France); Andreani, Olivier, E-mail: andreani.olivier@gmail.com [Department of Radiology, Hôpital Archet 2, Centre Hospitalo-Universitaire de Nice, Nice (France); Hauger, Olivier, E-mail: olivier.hauger@chubordeaux.fr [Department of Radiology, Hôpital Pellegrin, Centre Hospitalo-Universitaire de Bordeaux, Bordeaux (France); Cervantes, Elodie, E-mail: elodie.cervantes@live.fr [Department of Radiology, Hôpital Archet 2, Centre Hospitalo-Universitaire de Nice, Nice (France); Brunner, Philippe, E-mail: pbrunner@chpg.mc [Department of Radiology, Hôpital Princesse Grasse de Monaco (Monaco); Boileau, Pascal, E-mail: boileau.p@chu-nice.fr [Department of Orthopedic Surgery, Hôpital Archet 2, Centre Hospitalo-Universitaire de Nice, Nice (France); Amoretti, Nicolas, E-mail: amorettinicolas@yahoo.fr [Department of Radiology, Hôpital Archet 2, Centre Hospitalo-Universitaire de Nice, Nice (France)

2014-01-15

Objective: The treatment of vertebral split fractures remains controversial, consisting of either corset or internal fixation. The aim of this study was to evaluate the technical feasibility of CT- and fluoroscopy-guided percutaneous vertebroplasty in the treatment of vertebral split fractures. Materials and methods: Institutional review board approval and informed consent were obtained for this study. Sixty-two consecutive adult patients who had post-traumatic vertebral split fractures (A2 according to the AO classification) without neurological symptoms were prospectively treated by percutaneous vertebroplasty. All these procedures were performed by an interventional radiologist under computed tomography (CT) and fluoroscopy guidance by using only local anaesthesia. Postoperative outcome was assessed using the visual analogue scale (VAS) and Oswestry disability index (ODI) scores. Results: Vertebroplasty was performed on thoracic and lumbar vertebrae, creating a cement bridge between the displaced fragment and the rest of the vertebral body. Seven discal cement leakages (11%) were observed, without occurrence of adjacent vertebral compression fractures. The mean VAS measurements ± standard deviation (SD) significantly decreased from 7.9 ± 1.5 preoperatively to 3.3 ± 2.1 at 1 day, 2.2 ± 2.0 at 1 month, and 1.8 ± 1.4 at 6 months (P < 0.001). The mean ODI scores ± SD had also a significant improvement: 62.3 ± 17.2 preoperatively and 15.1 ± 6.0 at the 6-month follow-up (P < 0.001). Conclusion: This study suggests that type A2 vertebral fractures could be successfully treated by CT- and fluoroscopy-guided percutaneous vertebroplasty.

Vertebral split fractures: Technical feasibility of percutaneous vertebroplasty

International Nuclear Information System (INIS)

Huwart, Laurent; Foti, Pauline; Andreani, Olivier; Hauger, Olivier; Cervantes, Elodie; Brunner, Philippe; Boileau, Pascal; Amoretti, Nicolas

2014-01-01

Objective: The treatment of vertebral split fractures remains controversial, consisting of either corset or internal fixation. The aim of this study was to evaluate the technical feasibility of CT- and fluoroscopy-guided percutaneous vertebroplasty in the treatment of vertebral split fractures. Materials and methods: Institutional review board approval and informed consent were obtained for this study. Sixty-two consecutive adult patients who had post-traumatic vertebral split fractures (A2 according to the AO classification) without neurological symptoms were prospectively treated by percutaneous vertebroplasty. All these procedures were performed by an interventional radiologist under computed tomography (CT) and fluoroscopy guidance by using only local anaesthesia. Postoperative outcome was assessed using the visual analogue scale (VAS) and Oswestry disability index (ODI) scores. Results: Vertebroplasty was performed on thoracic and lumbar vertebrae, creating a cement bridge between the displaced fragment and the rest of the vertebral body. Seven discal cement leakages (11%) were observed, without occurrence of adjacent vertebral compression fractures. The mean VAS measurements ± standard deviation (SD) significantly decreased from 7.9 ± 1.5 preoperatively to 3.3 ± 2.1 at 1 day, 2.2 ± 2.0 at 1 month, and 1.8 ± 1.4 at 6 months (P < 0.001). The mean ODI scores ± SD had also a significant improvement: 62.3 ± 17.2 preoperatively and 15.1 ± 6.0 at the 6-month follow-up (P < 0.001). Conclusion: This study suggests that type A2 vertebral fractures could be successfully treated by CT- and fluoroscopy-guided percutaneous vertebroplasty

Contaminant exposure in terrestrial vertebrates

International Nuclear Information System (INIS)

Smith, Philip N.; Cobb, George P.; Godard-Codding, Celine; Hoff, Dale; McMurry, Scott T.; Rainwater, Thomas R.; Reynolds, Kevin D.

2007-01-01

Here we review mechanisms and factors influencing contaminant exposure among terrestrial vertebrate wildlife. There exists a complex mixture of biotic and abiotic factors that dictate potential for contaminant exposure among terrestrial and semi-terrestrial vertebrates. Chemical fate and transport in the environment determine contaminant bioaccessibility. Species-specific natural history characteristics and behavioral traits then play significant roles in the likelihood that exposure pathways, from source to receptor, are complete. Detailed knowledge of natural history traits of receptors considered in conjunction with the knowledge of contaminant behavior and distribution on a site are critical when assessing and quantifying exposure. We review limitations in our understanding of elements of exposure and the unique aspects of exposure associated with terrestrial and semi-terrestrial taxa. We provide insight on taxa-specific traits that contribute, or limit exposure to, transport phenomenon that influence exposure throughout terrestrial systems, novel contaminants, bioavailability, exposure data analysis, and uncertainty associated with exposure in wildlife risk assessments. Lastly, we identify areas related to exposure among terrestrial and semi-terrestrial organisms that warrant additional research. - Both biotic and abiotic factors determine chemical exposure for terrestrial vertebrates

Programmed Cell-to-Cell Variability in Ras Activity Triggers Emergent Behaviors during Mammary Epithelial Morphogenesis

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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.

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

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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.

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....

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

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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

Use of cervical vertebral dimensions for assessment of children growth

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Maria de Paula Caldas

2007-04-01

Full Text Available OBJECTIVE: The purpose of this study was to investigate whether skeletal maturation using cephalometric radiographs could be used in a Brazilian population. MATERIAL AND METHODS: The study population was selected from the files of the Oral Radiological Clinic of the Dental School of Piracicaba, Brazil and consisted of 128 girls and 110 boys (7.0 to 15.9 years old who had cephalometric and hand-wrist radiographs taken on the same day. Cervical vertebral bone age was evaluated using the method described by Mito and colleagues in 2002. Bone age was assessed by the Tanner-Whitehouse (TW3 method and was used as a gold standard to determine the reliability of cervical vertebral bone age. An analysis of variance and Tukey's post-hoc test were used to compare cervical vertebral bone age, bone age and chronological age at 5% significance level. RESULTS: The analysis of the Brazilian female children data showed that there was a statistically significant difference (p0.05 was found between cervical vertebral bone age and bone age. Differently, the analysis of the male children data revealed a statistically significant difference (p<0.05 between cervical vertebral bone age and bone age and between cervical vertebral bone age and chronological age (p<0.05. CONCLUSIONS: The findings of the present study suggest that the method for objectively evaluating skeletal maturation on cephalometric radiographs by determination of vertebral bone age can be applied to Brazilian females only. The development of a new method to objectively evaluate cervical vertebral bone age in males is needed.

Allergenicity of vertebrate tropomyosins: Challenging an immunological dogma.

Science.gov (United States)

González-Fernández, J; Daschner, A; Cuéllar, C

With the exception of tilapia tropomyosin, other anecdotic reports of tropomyosin recognition of vertebrate origin are generally not accompanied by clinical significance and a dogmatic idea is generally accepted about the inexistence of allergenicity of vertebrate tropomyosins, based mainly on sequence similarity evaluations with human tropomyosins. Recently, a specific work-up of a tropomyosin sensitised patient with seafood allergy, demonstrated that the IgE-recognition of tropomyosin from different fish species can be clinically relevant. We hypothesise that some vertebrate tropomyosins could be relevant allergens. The hypothesis is based on the molecular evolution of the proteins and it was tested by in silico methods. Fish, which are primitive vertebrates, could have tropomyosins similar to those of invertebrates. If the hypothesis is confirmed, tropomyosin should be included in different allergy diagnosis tools to improve the medical protocols and management of patients with digestive or cutaneous symptoms after fish intake. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Cervical vertebral and dental maturity in Turkish subjects.

Science.gov (United States)

Başaran, Güvenç; Ozer, Törün; Hamamci, Nihal

2007-04-01

The aim of this study was to investigate the relationships between the stages of calcification of teeth and the cervical vertebral maturity stages in Turkish subjects. A retrospective cross-sectional study was designed. The final study population consisted of 590 Turkish subjects. Statistical analysis of the data was performed with computer software. Spearman rank order correlation coefficients were used to assess the relationship between cervical vertebral and dental maturation. For a better understanding of the relationship between cervical vertebral maturation indexes and dental age, percentage distributions of the studied teeth were also calculated. Strict correlations were found between dental and cervical vertebral maturation of Turkish subjects. For males, the sequence from lowest to the highest was third molar, central incisor, canine, first premolar, second premolar, first molar, and second molar. For females, the sequence from lowest to the highest was third molar, canine, second premolar, first premolar, central incisor, first molar, and second molar. Dental maturation stages can be used as a reliable indicator of facial growth.

Corticotropin-releasing hormone: Mediator of vertebrate life stage transitions?

Science.gov (United States)

Watanabe, Yugo; Grommen, Sylvia V H; De Groef, Bert

2016-03-01

Hormones, particularly thyroid hormones and corticosteroids, play critical roles in vertebrate life stage transitions such as amphibian metamorphosis, hatching in precocial birds, and smoltification in salmonids. Since they synergistically regulate several metabolic and developmental processes that accompany vertebrate life stage transitions, the existence of extensive cross-communication between the adrenal/interrenal and thyroidal axes is not surprising. Synergies of corticosteroids and thyroid hormones are based on effects at the level of tissue hormone sensitivity and gene regulation. In addition, in representative nonmammalian vertebrates, corticotropin-releasing hormone (CRH) stimulates hypophyseal thyrotropin secretion, and thus functions as a common regulator of both the adrenal/interrenal and thyroidal axes to release corticosteroids and thyroid hormones. The dual function of CRH has been speculated to control or affect the timing of vertebrate life history transitions across taxa. After a brief overview of recent insights in the molecular mechanisms behind the synergic actions of thyroid hormones and corticosteroids during life stage transitions, this review examines the evidence for a possible role of CRH in controlling vertebrate life stage transitions. Copyright © 2016 Elsevier Inc. All rights reserved.

Cause analysis of missing diagnosis for vertebral fracture on lateral chest radiography

International Nuclear Information System (INIS)

Yu Wei; Yao Jinpeng; Lin Qiang; Mu Wenbin

2010-01-01

Objective: To analyze the cause of missing diagnosis for vertebral fracture on lateral chest radiography. Methods: Lateral chest radiographies of 1638 hospitalized patients (871 males and 767 females) were retrospectively reviewed for identifying vertebral fractures. Their ages ranged from 50 to 91 years with the mean of 63.5 years. Complains and application for chest radiography in all patients were not related to osteoporosis and vertebral fracture. Vertebral fracture and fracture severity were evaluated using Genant's semiquantitative visual method, taking approximately a 20%-25% vertebral height reduction as mild grade, 26%--40% as moderate grade and 41% or greater as severe grade. Evaluation results of the vertebral fracture, original X-ray reports, as well as medical records were compared for further analysis. Results: Eighty-four in 1638 patients showed vertebral fractures on the lateral chest radiographies. Of them, vertebral fractures were reported in 30 cases and 54 patients were not reported on their original X-ray reports. There were 63 vertebral fractures in 54 un-reported patients, most of which were single fracture (75% or 47/63). Grade I fracture accounted for 54% (34/63), Grade II fracture 33% (21/63), while 13% presented grade III fracture (8/63). In all 84 patients with vertebral fractures, only 5 cases (6%) underwent dual energy X-ray absorptiometry (DXA) measurement, 5 cases (6%) were recorded to have vertebral fractures on the medical papers, as well as 15 cases (18%) were prescribed drugs related to the osteoporosis when discharged from hospital. All drugs prescribed for the 15 patients were limited only to calcium. Conclusions: More attention should be paid to osteoporosis by doctors including radiologists. Vertebral fracture on lateral chest radiography should be completely diagnosed, which is helpful for both prevention and treatment. (authors)

Under-reporting of osteoporotic vertebral fractures on computed tomography

International Nuclear Information System (INIS)

Williams, Alexandra L.; Al-Busaidi, Aisha; Sparrow, Patrick J.; Adams, Judith E.; Whitehouse, Richard W.

2009-01-01

Purpose: Osteoporotic vertebral fractures are frequently asymptomatic. They are often not diagnosed clinically or radiologically. Despite this, prevalent osteoporotic vertebral fractures predict future osteoporotic fractures and are associated with increased mortality and morbidity. Appropriate management of osteoporosis can reduce future fracture risk. Fractures on lateral chest radiographs taken for other conditions are frequently overlooked by radiologists. Our aim was to assess the value of computed tomography (CT) in the diagnosis of vertebral fracture and identify the frequency with which significant fractures are missed. Materials and methods: The thoracic CT scans of 100 consecutive male and 100 consecutive female patients over 55 years were reviewed. CT images were acquired on General Electric Lightspeed multi-detector (MD) CT scanners (16 or 32 row) using 1.25 mm slice thickness. Midline sagittal images were reconstructed from the 3D volume images. The presence of moderate (25-40% height loss) or severe (>40% height loss) vertebral fractures between T1 and L1 was determined using an established semi-quantitative method and confirmed by morphological measurement. Results were compared with the formal CT report. Results: Scans of 192 patients were analysed (95 female; 97 male); mean age 70.1 years. Thirty-eight (19.8%) patients had one or more moderate to severe vertebral fractures. Only 5 (13%) were correctly reported as having osteoporotic fractures in the official report. The sensitivity of axial CT images to vertebral fracture was 0.35. Conclusion: Incidental osteoporotic vertebral fractures are under-reported on CT. The sensitivity of axial images in detecting these fractures is poor. Sagittal reformations are strongly recommended to improve the detection rate

Cochlear vertebral entrapment syndrome: a case report

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Liu Chinghsiung; Lin Shinnkuang E-mail: sk1943@adm.cgmh.org.tw; Chang Yeujhy

2001-11-01

The authors describe a patient with isolated involvement of vestibulocochlear nerve by a huge vascular loop from vertebral dolichoectasia. No other neurological deficit was found except for unilateral hearing loss. Abnormal brainstem auditory evoked potential study indicated a retrocochlear lesion. The brain computed tomography (CT) and magnetic resonance imaging (MRI) studies demonstrated an abnormally enhanced vascular lesion impinged on the left porus acusticus with a displacement of the brainstem to the right. There was no infarction in the brainstem. A cerebral angiography demonstrated a megadolichoectatic horizontal loop at the intracranial portion of the left vertebral artery. There was no thrombus or atherosclerosis in the vertebrobasilar system. A mechanical compression by a vascular loop is the only possible pathogenesis for hearing loss. The authors diagnose this condition as cochlear vertebral entrapment syndrome.

Imperfect Isolation: Factors and Filters Shaping Madagascar’s Extant Vertebrate Fauna

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Samonds, Karen E.; Godfrey, Laurie R.; Ali, Jason R.; Goodman, Steven M.; Vences, Miguel; Sutherland, Michael R.; Irwin, Mitchell T.; Krause, David W.

2013-01-01

Analyses of phylogenetic topology and estimates of divergence timing have facilitated a reconstruction of Madagascar’s colonization events by vertebrate animals, but that information alone does not reveal the major factors shaping the island’s biogeographic history. Here, we examine profiles of Malagasy vertebrate clades through time within the context of the island’s paleogeographical evolution to determine how particular events influenced the arrival of the island’s extant groups. First we compare vertebrate profiles on Madagascar before and after selected events; then we compare tetrapod profiles on Madagascar to contemporary tetrapod compositions globally. We show that changes from the Mesozoic to the Cenozoic in the proportions of Madagascar’s tetrapod clades (particularly its increase in the representation of birds and mammals) are tied to changes in their relative proportions elsewhere on the globe. Differences in the representation of vertebrate classes from the Mesozoic to the Cenozoic reflect the effects of extinction (i.e., the non-random susceptibility of the different vertebrate clades to purported catastrophic global events 65 million years ago), and new evolutionary opportunities for a subset of vertebrates with the relatively high potential for transoceanic dispersal potential. In comparison, changes in vertebrate class representation during the Cenozoic are minor. Despite the fact that the island’s isolation has resulted in high vertebrate endemism and a unique and taxonomically imbalanced extant vertebrate assemblage (both hailed as testimony to its long isolation), that isolation was never complete. Indeed, Madagascar’s extant tetrapod fauna owes more to colonization during the Cenozoic than to earlier arrivals. Madagascar’s unusual vertebrate assemblage needs to be understood with reference to the basal character of clades originating prior to the K-T extinction, as well as to the differential transoceanic dispersal advantage of

Association between vertebral cross-sectional area and lumbar lordosis angle in adolescents.

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Tishya A L Wren

Full Text Available Lumbar lordosis (LL is more prominent in women than in men, but the mechanisms responsible for this discrepancy are poorly defined. A recent study indicates that newborn girls have smaller vertebral cross-sectional area (CSA when compared to boys-a difference that persists throughout life and is independent of body size. We determined the relations between vertebral cross-sectional area (CSA and LL angle and whether sex differences in lumbar lordosis are related to sex differences in vertebral CSA. Using multi-planar magnetic resonance imaging (MRI, we measured vertebral cross-sectional area (CSA and vertebral height of the spine of 40 healthy boys and 40 girls, ages 9-13 years. Measures of the CSA of the lumbar vertebrae significantly differed between sexes (9.38 ± 1.46 vs. 7.93 ± 0.69 in boys and girls, respectively; P < 0.0001, while the degree of LL was significantly greater in girls than in boys (23.7 ± 6.1 vs. 27.6 ± 8.0 in boys and girls, respectively; P = 0.02. When all subjects were analyzed together, values for LL angle were negatively correlated to vertebral CSA (r = -0.47; P < 0.0001; this was also true when boys and girls were analyzed separately. Multivariate regression analysis indicated that vertebral CSA was independently associated with LL, even after accounting for sex, age, height or vertebral height, and weight. Similar negative relations were present when thoracic vertebrae were analyzed (Model P < 0.0001, R2 = 0.37, thoracic vertebral CSA slope P < 0.0001, suggesting that deficient vertebral cross-sectional dimensions are not merely the consequence of the anterior lumbar curvature. We conclude that vertebral CSA is negatively associated with LL, and that the greater degree of LL in females could, at least in part, be due to smaller vertebral cross-sectional dimensions. Studies are needed to examine the potential relations between vertebral CSA and spinal conditions known to be associated with increased LL, such as

Association between vertebral cross-sectional area and lumbar lordosis angle in adolescents.

Science.gov (United States)

Wren, Tishya A L; Aggabao, Patricia C; Poorghasamians, Ervin; Chavez, Thomas A; Ponrartana, Skorn; Gilsanz, Vicente

2017-01-01

Lumbar lordosis (LL) is more prominent in women than in men, but the mechanisms responsible for this discrepancy are poorly defined. A recent study indicates that newborn girls have smaller vertebral cross-sectional area (CSA) when compared to boys-a difference that persists throughout life and is independent of body size. We determined the relations between vertebral cross-sectional area (CSA) and LL angle and whether sex differences in lumbar lordosis are related to sex differences in vertebral CSA. Using multi-planar magnetic resonance imaging (MRI), we measured vertebral cross-sectional area (CSA) and vertebral height of the spine of 40 healthy boys and 40 girls, ages 9-13 years. Measures of the CSA of the lumbar vertebrae significantly differed between sexes (9.38 ± 1.46 vs. 7.93 ± 0.69 in boys and girls, respectively; P < 0.0001), while the degree of LL was significantly greater in girls than in boys (23.7 ± 6.1 vs. 27.6 ± 8.0 in boys and girls, respectively; P = 0.02). When all subjects were analyzed together, values for LL angle were negatively correlated to vertebral CSA (r = -0.47; P < 0.0001); this was also true when boys and girls were analyzed separately. Multivariate regression analysis indicated that vertebral CSA was independently associated with LL, even after accounting for sex, age, height or vertebral height, and weight. Similar negative relations were present when thoracic vertebrae were analyzed (Model P < 0.0001, R2 = 0.37, thoracic vertebral CSA slope P < 0.0001), suggesting that deficient vertebral cross-sectional dimensions are not merely the consequence of the anterior lumbar curvature. We conclude that vertebral CSA is negatively associated with LL, and that the greater degree of LL in females could, at least in part, be due to smaller vertebral cross-sectional dimensions. Studies are needed to examine the potential relations between vertebral CSA and spinal conditions known to be associated with increased LL, such as spondylolysis

Pleistocene vertebrates of the Yukon Territory

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Harington, C. R.

2011-08-01

Unglaciated parts of the Yukon constitute one of the most important areas in North America for yielding Pleistocene vertebrate fossils. Nearly 30 vertebrate faunal localities are reviewed spanning a period of about 1.6 Ma (million years ago) to the close of the Pleistocene some 10 000 BP (radiocarbon years before present, taken as 1950). The vertebrate fossils represent at least 8 species of fishes, 1 amphibian, 41 species of birds and 83 species of mammals. Dominant among the large mammals are: steppe bison ( Bison priscus), horse ( Equus sp.), woolly mammoth ( Mammuthus primigenius), and caribou ( Rangifer tarandus) - signature species of the Mammoth Steppe fauna ( Fig. 1), which was widespread from the British Isles, through northern Europe, and Siberia to Alaska, Yukon and adjacent Northwest Territories. The Yukon faunas extend from Herschel Island in the north to Revenue Creek in the south and from the Alaskan border in the west to Ketza River in the east. The Yukon holds evidence of the earliest-known people in North America. Artifacts made from bison, mammoth and caribou bones from Bluefish Caves, Old Crow Basin and Dawson City areas show that people had a substantial knowledge of making and using bone tools at least by 25 000 BP, and possibly as early as 40 000 BP. A suggested chronological sequence of Yukon Pleistocene vertebrates ( Table 1) facilitates comparison of selected faunas and indicates the known duration of various taxa.

Collective cell migration drives morphogenesis of the kidney nephron.

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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.

Distinct subsets of Eve-positive pericardial cells stabilise cardiac outflow and contribute to Hox gene-triggered heart morphogenesis in Drosophila.