WorldWideScience

Sample records for mesoderm

  1. Mesoderm layer formation in Xenopus and Drosophila gastrulation

    International Nuclear Information System (INIS)

    Winklbauer, Rudolf; Müller, H-Arno J

    2011-01-01

    During gastrulation, the mesoderm spreads out between ectoderm and endoderm to form a mesenchymal cell layer. Surprisingly the underlying principles of mesoderm layer formation are very similar in evolutionarily distant species like the fruit fly, Drosophila melanogaster, and the frog, Xenopus laevis, in which the molecular and the cellular basis of mesoderm layer formation have been extensively studied. Complementary expression of growth factors in the ectoderm and their receptors in the mesoderm act to orient cellular protrusive activities and direct cell movement, leading to radial cell intercalation and the spreading of the mesoderm layer. This mechanism is contrasted with generic physical mechanisms of tissue spreading that consider the adhesive and physical properties of the cells and tissues. Both mechanisms need to be integrated to orchestrate mesenchymal morphogenesis

  2. Insights from diploblasts; the evolution of mesoderm and muscle.

    Science.gov (United States)

    Burton, Patrick Michael

    2008-01-15

    The origin of both mesoderm and muscle are central questions in metazoan evolution. The majority of metazoan phyla are triploblasts, possessing three discrete germ layers. Attention has therefore been focused on two outgroups to triploblasts, Cnidaria and Ctenophora. Modern texts describe these taxa as diploblasts, lacking a mesodermal germ layer. However, some members of Medusozoa, one of two subphyla within Cnidaria, possess tissue independent of either the ectoderm or endoderm referred to as the entocodon. Furthermore, members of both Cnidaria and Ctenophora have been described as possessing striated muscle, a mesodermal derivative. While it is widely accepted that the ancestor of Eumetazoa was diploblastic, homology of the entocodon and mesoderm as well as striated muscle within Eumetazoa has been suggested. This implies a potential triploblastic ancestor of Eumetazoa possessing striated muscle. In the following review, I examine the evidence for homology of both muscle and mesoderm. Current data support a diploblastic ancestor of cnidarians, ctenophores, and triploblasts lacking striated muscle.

  3. Analysis of a Caenorhabditis elegans Twist homolog identifies conserved and divergent aspects of mesodermal patterning

    OpenAIRE

    Harfe, Brian D.; Gomes, Ana Vaz; Kenyon, Cynthia; Liu, Jun; Krause, Michael; Fire, Andrew

    1998-01-01

    Mesodermal development is a multistep process in which cells become increasingly specialized to form specific tissue types. In Drosophila and mammals, proper segregation and patterning of the mesoderm involves the bHLH factor Twist. We investigated the activity of a Twist-related factor, CeTwist, during Caenorhabditis elegans mesoderm development. Embryonic mesoderm in C. elegans derives from a number of distinct founder cells that are specified during the early lineages; in contrast, a singl...

  4. File list: Oth.Emb.05.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.05.AllAg.Pre-somitic_mesoderm mm9 TFs and others Embryo Pre-somitic mesoder...m http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.05.AllAg.Pre-somitic_mesoderm.bed ...

  5. File list: Pol.Emb.20.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.20.AllAg.Pre-somitic_mesoderm mm9 RNA polymerase Embryo Pre-somitic mesoder...m http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.20.AllAg.Pre-somitic_mesoderm.bed ...

  6. File list: Unc.Emb.20.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Emb.20.AllAg.Pre-somitic_mesoderm mm9 Unclassified Embryo Pre-somitic mesoderm ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Emb.20.AllAg.Pre-somitic_mesoderm.bed ...

  7. File list: Unc.Emb.10.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Emb.10.AllAg.Pre-somitic_mesoderm mm9 Unclassified Embryo Pre-somitic mesoderm ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Emb.10.AllAg.Pre-somitic_mesoderm.bed ...

  8. File list: ALL.Emb.10.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.10.AllAg.Pre-somitic_mesoderm mm9 All antigens Embryo Pre-somitic mesoderm ...SRX474258,SRX474259 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.10.AllAg.Pre-somitic_mesoderm.bed ...

  9. File list: His.Emb.50.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Emb.50.AllAg.Pre-somitic_mesoderm mm9 Histone Embryo Pre-somitic mesoderm SRX47...4258,SRX474259 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Emb.50.AllAg.Pre-somitic_mesoderm.bed ...

  10. File list: DNS.Emb.20.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Emb.20.AllAg.Pre-somitic_mesoderm mm9 DNase-seq Embryo Pre-somitic mesoderm htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Emb.20.AllAg.Pre-somitic_mesoderm.bed ...

  11. File list: Pol.Emb.10.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.10.AllAg.Pre-somitic_mesoderm mm9 RNA polymerase Embryo Pre-somitic mesoder...m http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.10.AllAg.Pre-somitic_mesoderm.bed ...

  12. File list: Unc.Emb.50.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Emb.50.AllAg.Pre-somitic_mesoderm mm9 Unclassified Embryo Pre-somitic mesoderm ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Emb.50.AllAg.Pre-somitic_mesoderm.bed ...

  13. File list: DNS.Emb.50.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Emb.50.AllAg.Pre-somitic_mesoderm mm9 DNase-seq Embryo Pre-somitic mesoderm htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Emb.50.AllAg.Pre-somitic_mesoderm.bed ...

  14. File list: Unc.Emb.05.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Emb.05.AllAg.Pre-somitic_mesoderm mm9 Unclassified Embryo Pre-somitic mesoderm ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Emb.05.AllAg.Pre-somitic_mesoderm.bed ...

  15. File list: Pol.Emb.05.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.05.AllAg.Pre-somitic_mesoderm mm9 RNA polymerase Embryo Pre-somitic mesoder...m http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.05.AllAg.Pre-somitic_mesoderm.bed ...

  16. File list: His.Emb.05.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Emb.05.AllAg.Pre-somitic_mesoderm mm9 Histone Embryo Pre-somitic mesoderm SRX47...4258,SRX474259 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Emb.05.AllAg.Pre-somitic_mesoderm.bed ...

  17. File list: Oth.Emb.50.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.50.AllAg.Pre-somitic_mesoderm mm9 TFs and others Embryo Pre-somitic mesoder...m http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.50.AllAg.Pre-somitic_mesoderm.bed ...

  18. File list: Oth.Emb.20.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.20.AllAg.Pre-somitic_mesoderm mm9 TFs and others Embryo Pre-somitic mesoder...m http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.20.AllAg.Pre-somitic_mesoderm.bed ...

  19. File list: ALL.Emb.20.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.20.AllAg.Pre-somitic_mesoderm mm9 All antigens Embryo Pre-somitic mesoderm ...SRX474258,SRX474259 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.20.AllAg.Pre-somitic_mesoderm.bed ...

  20. File list: His.Emb.20.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Emb.20.AllAg.Pre-somitic_mesoderm mm9 Histone Embryo Pre-somitic mesoderm SRX47...4258,SRX474259 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Emb.20.AllAg.Pre-somitic_mesoderm.bed ...

  1. File list: Oth.Emb.10.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.10.AllAg.Pre-somitic_mesoderm mm9 TFs and others Embryo Pre-somitic mesoder...m http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.10.AllAg.Pre-somitic_mesoderm.bed ...

  2. File list: ALL.Emb.50.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.50.AllAg.Pre-somitic_mesoderm mm9 All antigens Embryo Pre-somitic mesoderm ...SRX474258,SRX474259 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.50.AllAg.Pre-somitic_mesoderm.bed ...

  3. File list: His.Emb.10.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Emb.10.AllAg.Pre-somitic_mesoderm mm9 Histone Embryo Pre-somitic mesoderm SRX47...4258,SRX474259 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Emb.10.AllAg.Pre-somitic_mesoderm.bed ...

  4. File list: Pol.Emb.50.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.50.AllAg.Pre-somitic_mesoderm mm9 RNA polymerase Embryo Pre-somitic mesoder...m http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.50.AllAg.Pre-somitic_mesoderm.bed ...

  5. File list: DNS.Emb.10.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Emb.10.AllAg.Pre-somitic_mesoderm mm9 DNase-seq Embryo Pre-somitic mesoderm htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Emb.10.AllAg.Pre-somitic_mesoderm.bed ...

  6. File list: DNS.Emb.05.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Emb.05.AllAg.Pre-somitic_mesoderm mm9 DNase-seq Embryo Pre-somitic mesoderm htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Emb.05.AllAg.Pre-somitic_mesoderm.bed ...

  7. File list: ALL.Emb.05.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.05.AllAg.Pre-somitic_mesoderm mm9 All antigens Embryo Pre-somitic mesoderm ...SRX474258,SRX474259 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.05.AllAg.Pre-somitic_mesoderm.bed ...

  8. File list: NoD.PSC.05.AllAg.mESC_derived_mesodermal_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.PSC.05.AllAg.mESC_derived_mesodermal_cells mm9 No description Pluripotent stem cell mESC derived meso...dermal cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.PSC.05.AllAg.mESC_derived_mesodermal_cells.bed ...

  9. File list: NoD.PSC.10.AllAg.mESC_derived_mesodermal_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.PSC.10.AllAg.mESC_derived_mesodermal_cells mm9 No description Pluripotent stem cell mESC derived meso...dermal cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.PSC.10.AllAg.mESC_derived_mesodermal_cells.bed ...

  10. File list: Pol.PSC.20.AllAg.mESC_derived_mesodermal_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.PSC.20.AllAg.mESC_derived_mesodermal_cells mm9 RNA polymerase Pluripotent stem cell mESC derived meso...dermal cells SRX305931,SRX305930 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.PSC.20.AllAg.mESC_derived_mesodermal_cells.bed ...

  11. File list: Pol.PSC.05.AllAg.mESC_derived_mesodermal_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.PSC.05.AllAg.mESC_derived_mesodermal_cells mm9 RNA polymerase Pluripotent stem cell mESC derived meso...dermal cells SRX305930,SRX305931 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.PSC.05.AllAg.mESC_derived_mesodermal_cells.bed ...

  12. File list: NoD.PSC.20.AllAg.mESC_derived_mesodermal_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.PSC.20.AllAg.mESC_derived_mesodermal_cells mm9 No description Pluripotent stem cell mESC derived meso...dermal cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.PSC.20.AllAg.mESC_derived_mesodermal_cells.bed ...

  13. File list: Pol.PSC.10.AllAg.mESC_derived_mesodermal_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.PSC.10.AllAg.mESC_derived_mesodermal_cells mm9 RNA polymerase Pluripotent stem cell mESC derived meso...dermal cells SRX305931,SRX305930 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.PSC.10.AllAg.mESC_derived_mesodermal_cells.bed ...

  14. File list: Pol.PSC.50.AllAg.mESC_derived_mesodermal_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.PSC.50.AllAg.mESC_derived_mesodermal_cells mm9 RNA polymerase Pluripotent stem cell mESC derived meso...dermal cells SRX305931,SRX305930 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.PSC.50.AllAg.mESC_derived_mesodermal_cells.bed ...

  15. File list: DNS.PSC.10.AllAg.mESC_derived_mesodermal_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.PSC.10.AllAg.mESC_derived_mesodermal_cells mm9 DNase-seq Pluripotent stem cell mESC derived meso...dermal cells SRX404483,SRX404484 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.PSC.10.AllAg.mESC_derived_mesodermal_cells.bed ...

  16. File list: NoD.PSC.50.AllAg.mESC_derived_mesodermal_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.PSC.50.AllAg.mESC_derived_mesodermal_cells mm9 No description Pluripotent stem cell mESC derived meso...dermal cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.PSC.50.AllAg.mESC_derived_mesodermal_cells.bed ...

  17. File list: DNS.PSC.20.AllAg.mESC_derived_mesodermal_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.PSC.20.AllAg.mESC_derived_mesodermal_cells mm9 DNase-seq Pluripotent stem cell mESC derived meso...dermal cells SRX404483,SRX404484 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.PSC.20.AllAg.mESC_derived_mesodermal_cells.bed ...

  18. File list: DNS.PSC.05.AllAg.mESC_derived_mesodermal_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.PSC.05.AllAg.mESC_derived_mesodermal_cells mm9 DNase-seq Pluripotent stem cell mESC derived meso...dermal cells SRX404483,SRX404484 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.PSC.05.AllAg.mESC_derived_mesodermal_cells.bed ...

  19. File list: NoD.Emb.10.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.10.AllAg.Pre-somitic_mesoderm mm9 No description Embryo Pre-somitic mesoder...m http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.10.AllAg.Pre-somitic_mesoderm.bed ...

  20. File list: NoD.Emb.20.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.20.AllAg.Pre-somitic_mesoderm mm9 No description Embryo Pre-somitic mesoder...m http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.20.AllAg.Pre-somitic_mesoderm.bed ...

  1. File list: InP.Emb.20.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.20.AllAg.Pre-somitic_mesoderm mm9 Input control Embryo Pre-somitic mesoderm... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.20.AllAg.Pre-somitic_mesoderm.bed ...

  2. File list: InP.Emb.10.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.10.AllAg.Pre-somitic_mesoderm mm9 Input control Embryo Pre-somitic mesoderm... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.10.AllAg.Pre-somitic_mesoderm.bed ...

  3. File list: NoD.Emb.50.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.50.AllAg.Pre-somitic_mesoderm mm9 No description Embryo Pre-somitic mesoder...m http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.50.AllAg.Pre-somitic_mesoderm.bed ...

  4. File list: InP.Emb.50.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.50.AllAg.Pre-somitic_mesoderm mm9 Input control Embryo Pre-somitic mesoderm... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.50.AllAg.Pre-somitic_mesoderm.bed ...

  5. File list: InP.Emb.05.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.05.AllAg.Pre-somitic_mesoderm mm9 Input control Embryo Pre-somitic mesoderm... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.05.AllAg.Pre-somitic_mesoderm.bed ...

  6. Growth factors and early mesoderm morphogenesis: insights from the sea urchin embryo.

    Science.gov (United States)

    Adomako-Ankomah, Ashrifia; Ettensohn, Charles A

    2014-03-01

    The early morphogenesis of the mesoderm is critically important in establishing the body plan of the embryo. Recent research has led to a better understanding of the mechanisms that underlie this process, and growth factor signaling pathways have emerged as key regulators of the directional movements of mesoderm cells during gastrulation. In this review, we undertake a comparative analysis of the various essential functions of growth factor signaling pathways in regulating early mesoderm morphogenesis, with an emphasis on recent advances in the sea urchin embryo. We focus on the roles of the vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) pathways in the migration of primary mesenchyme cells and the formation of the embryonic endoskeleton. We compare the functions of VEGF and FGF in sea urchins with the roles that these and other growth factors play in regulating mesoderm migration during gastrulation in Drosophila and vertebrates. Copyright © 2014 Wiley Periodicals, Inc.

  7. The mesenchymal architecture of the cranial mesoderm of mouse embryos is disrupted by the loss of Twist1 function.

    Science.gov (United States)

    Bildsoe, Heidi; Loebel, David A F; Jones, Vanessa J; Hor, Angelyn C C; Braithwaite, Antony W; Chen, You-Tzung; Behringer, Richard R; Tam, Patrick P L

    2013-02-15

    The basic helix-loop-helix transcription factor Twist1 is a key regulator of craniofacial development. Twist1-null mouse embryos exhibit failure of cephalic neural tube closure and abnormal head development and die at E11.0. To dissect the function of Twist1 in the cranial mesoderm beyond mid-gestation, we used Mesp1-Cre to delete Twist1 in the anterior mesoderm, which includes the progenitors of the cranial mesoderm. Deletion of Twist1 in mesoderm cells resulted in loss and malformations of the cranial mesoderm-derived skeleton. Loss of Twist1 in the mesoderm also resulted in a failure to fully segregate the mesoderm and the neural crest cells, and the malformation of some cranial neural crest-derived tissues. The development of extraocular muscles was compromised whereas the differentiation of branchial arch muscles was not affected, indicating a differential requirement for Twist1 in these two types of craniofacial muscle. A striking effect of the loss of Twist1 was the inability of the mesodermal cells to maintain their mesenchymal characteristics, and the acquisition of an epithelial-like morphology. Our findings point to a role of Twist1 in maintaining the mesenchyme architecture and the progenitor state of the mesoderm, as well as mediating mesoderm-neural crest interactions in craniofacial development. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis.

    Science.gov (United States)

    Harel, Itamar; Maezawa, Yoshiro; Avraham, Roi; Rinon, Ariel; Ma, Hsiao-Yen; Cross, Joe W; Leviatan, Noam; Hegesh, Julius; Roy, Achira; Jacob-Hirsch, Jasmine; Rechavi, Gideon; Carvajal, Jaime; Tole, Shubha; Kioussi, Chrissa; Quaggin, Susan; Tzahor, Eldad

    2012-11-13

    The search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory network of a set of transcription factors expressed in the PM that initiates heart and craniofacial organogenesis. Genetic perturbation of this network in mice resulted in heart and craniofacial muscle defects, revealing robust cross-regulation between its members. We identified Lhx2 as a previously undescribed player during cardiac and pharyngeal muscle development. Lhx2 and Tcf21 genetically interact with Tbx1, the major determinant in the etiology of DiGeorge/velo-cardio-facial/22q11.2 deletion syndrome. Furthermore, knockout of these genes in the mouse recapitulates specific cardiac features of this syndrome. We suggest that PM-derived cardiogenesis and myogenesis are network properties rather than properties specific to individual PM members. These findings shed new light on the developmental underpinnings of congenital defects.

  9. The Mesodermal Expression of rolling stone (rost) Is Essential for Myoblast Fusion in Drosophila and Encodes a Potential Transmembrane Protein

    OpenAIRE

    Paululat, Achim; Goubeaud, Anette; Damm, Christine; Knirr, Stefan; Burchard, Susanne; Renkawitz-Pohl, Renate

    1997-01-01

    In homozygous rolling stone embryos, the fusion of myoblasts to syncytial myotubes is diminished. Nevertheless, the visceral mesoderm, the heart mesoderm, and few somatic muscles are properly formed. Thus, we postulate a central role of rolling stone for the fusion process within the somatic mesoderm. We have cloned the rolling stone gene, and the deduced protein sequence is in accordance with a transmembrane protein, which agrees with the enrichment of Rost in the membrane fraction of Drosop...

  10. Wingless effects mesoderm patterning and ectoderm segmentation events via induction of its downstream target sloppy paired.

    Science.gov (United States)

    Lee, H H; Frasch, M

    2000-12-01

    Inactivation of either the secreted protein Wingless (Wg) or the forkhead domain transcription factor Sloppy Paired (Slp) has been shown to produce similar effects in the developing Drosophila embryo. In the ectoderm, both gene products are required for the formation of the segmental portions marked by naked cuticle. In the mesoderm, Wg and Slp activities are crucial for the suppression of bagpipe (bap), and hence visceral mesoderm formation, and the promotion of somatic muscle and heart formation within the anterior portion of each parasegment. In this report, we show that, during these developmental processes, wg and slp act in a common pathway in which slp serves as a direct target of Wg signals that mediates Wg effects in both germ layers. We present evidence that the induction of slp by Wg involves binding of the Wg effector Pangolin (Drosophila Lef-1/TCF) to multiple binding sites within a Wg-responsive enhancer that is located in 5' flanking regions of the slp1 gene. Based upon our genetic and molecular analysis, we conclude that Wg signaling induces striped expression of Slp in the mesoderm. Mesodermal Slp is then sufficient to abrogate the induction of bagpipe by Dpp/Tinman, which explains the periodic arrangement of trunk visceral mesoderm primordia in wild type embryos. Conversely, mesodermal Slp is positively required, although not sufficient, for the specification of somatic muscle and heart progenitors. We propose that Wg-induced slp provides striped mesodermal domains with the competence to respond to subsequent slp-independent Wg signals that induce somatic muscle and heart progenitors. We also propose that in wg-expressing ectodermal cells, slp is an integral component in an autocrine feedback loop of Wg signaling.

  11. FGF signal interpretation is directed by Sprouty and Spred proteins during mesoderm formation.

    Science.gov (United States)

    Sivak, Jeremy M; Petersen, Lars F; Amaya, Enrique

    2005-05-01

    Vertebrate gastrulation requires coordination of mesoderm specification with morphogenetic movements. While both of these processes require FGF signaling, it is not known how mesoderm specification and cell movements are coordinated during gastrulation. The related Sprouty and Spred protein families are recently discovered regulators of receptor tyrosine kinase signaling. We identified two genes for each family in Xenopus tropicalis: Xtsprouty1, Xtsprouty2, Xtspred1, and Xtspred2. In gain- and loss-of-function experiments we show that XtSprouty and XtSpred proteins modulate different signaling pathways downstream of the FGF receptor (FGFR), and consequently different developmental processes. Notably, XtSproutys inhibit morphogenesis and Ca(2+) and PKCdelta signaling, leaving MAPK activation and mesoderm specification intact. In contrast, XtSpreds inhibit MAPK activation and mesoderm specification, with little effect on Ca(2+) or PKCdelta signaling. These differences, combined with the timing of their developmental expression, suggest a mechanism to switch FGFR signal interpretation to coordinate mesoderm formation and cell movements during gastrulation.

  12. Alk3 controls nephron number and androgen production via lineage-specific effects in intermediate mesoderm.

    Science.gov (United States)

    Di Giovanni, Valeria; Alday, Adrian; Chi, Lijun; Mishina, Yuji; Rosenblum, Norman D

    2011-07-01

    The mammalian kidney and male reproductive system are both derived from the intermediate mesoderm. The spatial and temporal expression of bone morphogenetic protein (BMP) 2 and BMP4 and their cognate receptor, activin like kinase 3 (ALK3), suggests a functional role for BMP-ALK3 signaling during formation of intermediate mesoderm-derivative organs. Here, we define cell autonomous functions for Alk3 in the kidney and male gonad in mice with CRE-mediated Alk3 inactivation targeted to intermediate mesoderm progenitors (Alk3(IMP null)). Alk3-deficient mice exhibit simple renal hypoplasia characterized by decreases in both kidney size and nephron number but normal tissue architecture. These defects are preceded by a decreased contribution of Alk3-deleted cells to the metanephric blastema and reduced expression of Osr1 and SIX2, which mark nephron progenitor cells. Mutant mice are also characterized by defects in intermediate mesoderm-derived genital tissues with fewer mesonephric tubules and testicular Leydig cells, epithelial vacuolization in the postnatal corpus epididymis, and decreased serum testosterone levels and reduced fertility. Analysis of ALK3-dependent signaling effectors revealed lineage-specific reduction of phospho-p38 MAPK in metanephric mesenchyme and phospho-SMAD1/5/8 in the testis. Together, these results demonstrate a requirement for Alk3 in distinct progenitor cell populations derived from the intermediate mesoderm.

  13. Traffic jam in the primitive streak: the role of defective mesoderm migration in birth defects.

    Science.gov (United States)

    Herion, Nils J; Salbaum, J Michael; Kappen, Claudia

    2014-08-01

    Gastrulation is the process in which the three germ layers are formed that contribute to the formation of all major tissues in the developing embryo. We here review mouse genetic models in which defective gastrulation leads to mesoderm insufficiencies in the embryo. Depending on severity of the abnormalities, the outcomes range from incompatible with embryonic survival to structural birth defects, such as heart defects, spina bifida, or caudal dysgenesis. The combined evidence from the mutant models supports the notion that these congenital anomalies can originate from perturbations of mesoderm specification, epithelial-mesenchymal transition, and mesodermal cell migration. Knowledge about the molecular pathways involved may help to improve strategies for the prevention of major structural birth defects. © 2014 Wiley Periodicals, Inc.

  14. A Gene Regulatory Network Balances Neural and Mesoderm Specification during Vertebrate Trunk Development.

    Science.gov (United States)

    Gouti, Mina; Delile, Julien; Stamataki, Despina; Wymeersch, Filip J; Huang, Yali; Kleinjung, Jens; Wilson, Valerie; Briscoe, James

    2017-05-08

    Transcriptional networks, regulated by extracellular signals, control cell fate decisions and determine the size and composition of developing tissues. One example is the network controlling bipotent neuromesodermal progenitors (NMPs) that fuel embryo elongation by generating spinal cord and trunk mesoderm tissue. Here, we use single-cell transcriptomics to identify the molecular signature of NMPs and reverse engineer the mechanism that regulates their differentiation. Together with genetic perturbations, this reveals a transcriptional network that integrates opposing retinoic acid (RA) and Wnt signals to determine the rate at which cells enter and exit the NMP state. RA, produced by newly generated mesodermal cells, provides feedback that initiates NMP generation and induces neural differentiation, thereby coordinating the production of neural and mesodermal tissue. Together, the data define a regulatory network architecture that balances the generation of different cell types from bipotential progenitors in order to facilitate orderly axis elongation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. Identification of novel genes affecting mesoderm formation and morphogenesis through an enhanced large scale functional screen in Xenopus.

    Science.gov (United States)

    Chen, Jun-An; Voigt, Jana; Gilchrist, Mike; Papalopulu, Nancy; Amaya, Enrique

    2005-03-01

    The formation of mesoderm is an important developmental process of vertebrate embryos, which can be broken down into several steps; mesoderm induction, patterning, morphogenesis and differentiation. Although mesoderm formation in Xenopus has been intensively studied, much remains to be learned about the molecular events responsible for each of these steps. Furthermore, the interplay between mesoderm induction, patterning and morphogenesis remains obscure. Here, we describe an enhanced functional screen in Xenopus designed for large-scale identification of genes controlling mesoderm formation. In order to improve the efficiency of the screen, we used a Xenopus tropicalis unique set of cDNAs, highly enriched in full-length clones. The screening strategy incorporates two mesodermal markers, Xbra and Xmyf-5, to assay for cell fate specification and patterning, respectively. In addition we looked for phenotypes that would suggest effects in morphogenesis, such as gastrulation defects and shortened anterior-posterior axis. Out of 1728 full-length clones we isolated 82 for their ability to alter the phenotype of tadpoles and/or the expression of Xbra and Xmyf-5. Many of the clones gave rise to similar misexpression phenotypes (synphenotypes) and many of the genes within each synphenotype group appeared to be involved in similar pathways. We determined the expression pattern of the 82 genes and found that most of the genes were regionalized and expressed in mesoderm. We expect that many of the genes identified in this screen will be important in mesoderm formation.

  16. File list: InP.PSC.50.AllAg.mESC_derived_mesodermal_cells [Chip-atlas[Archive

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  1. File list: InP.PSC.20.AllAg.mESC_derived_mesodermal_cells [Chip-atlas[Archive

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  15. File list: His.PSC.20.AllAg.mESC_derived_mesodermal_cells [Chip-atlas[Archive

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  16. Transcriptional targets of TWIST1 in the cranial mesoderm regulate cell-matrix interactions and mesenchyme maintenance

    NARCIS (Netherlands)

    Bildsoe, Heidi; Fan, Xiaochen; Wilkie, Emilie E.; Ashoti, Ator; Jones, Vanessa J.; Power, Melinda; Qin, Jing; Wang, Junwen; Tam, Patrick P L; Loebel, David A F

    2016-01-01

    TWIST1, a basic helix-loop-helix transcription factor is essential for the development of cranial mesoderm and cranial neural crest-derived craniofacial structures. We have previously shown that, in the absence of TWIST1, cells within the cranial mesoderm adopt an abnormal epithelial configuration

  17. Reciprocal endoderm-mesoderm interactions mediated by fgf24 and fgf10 govern pancreas development.

    Science.gov (United States)

    Manfroid, Isabelle; Delporte, François; Baudhuin, Ariane; Motte, Patrick; Neumann, Carl J; Voz, Marianne L; Martial, Joseph A; Peers, Bernard

    2007-11-01

    In amniotes, the pancreatic mesenchyme plays a crucial role in pancreatic epithelium growth, notably through the secretion of fibroblast growth factors. However, the factors involved in the formation of the pancreatic mesenchyme are still largely unknown. In this study, we characterize, in zebrafish embryos, the pancreatic lateral plate mesoderm, which is located adjacent to the ventral pancreatic bud and is essential for its specification and growth. We firstly show that the endoderm, by expressing the fgf24 gene at early stages, triggers the patterning of the pancreatic lateral plate mesoderm. Based on the expression of isl1, fgf10 and meis genes, this tissue is analogous to the murine pancreatic mesenchyme. Secondly, Fgf10 acts redundantly with Fgf24 in the pancreatic lateral plate mesoderm and they are both required to specify the ventral pancreas. Our results unveil sequential signaling between the endoderm and mesoderm that is critical for the specification and growth of the ventral pancreas, and explain why the zebrafish ventral pancreatic bud generates the whole exocrine tissue.

  18. Changes in glycosaminoglycan structure on differentiation of human embryonic stem cells towards mesoderm and endoderm lineages.

    Science.gov (United States)

    Gasimli, Leyla; Hickey, Anne Marie; Yang, Bo; Li, Guoyun; dela Rosa, Mitche; Nairn, Alison V; Kulik, Michael J; Dordick, Jonathan S; Moremen, Kelley W; Dalton, Stephen; Linhardt, Robert J

    2014-06-01

    Proteoglycans are found on the cell surface and in the extracellular matrix, and serve as prime sites for interaction with signaling molecules. Proteoglycans help regulate pathways that control stem cell fate, and therefore represent an excellent tool to manipulate these pathways. Despite their importance, there is a dearth of data linking glycosaminoglycan structure within proteoglycans with stem cell differentiation. Human embryonic stem cell line WA09 (H9) was differentiated into early mesoderm and endoderm lineages, and the glycosaminoglycanomic changes accompanying these transitions were studied using transcript analysis, immunoblotting, immunofluorescence and disaccharide analysis. Pluripotent H9 cell lumican had no glycosaminoglycan chains whereas in splanchnic mesoderm lumican was glycosaminoglycanated. H9 cells have primarily non-sulfated heparan sulfate chains. On differentiation towards splanchnic mesoderm and hepatic lineages N-sulfo group content increases. Differences in transcript expression of NDST1, HS6ST2 and HS6ST3, three heparan sulfate biosynthetic enzymes, within splanchnic mesoderm cells compared to H9 cells correlate to changes in glycosaminoglycan structure. Differentiation of embryonic stem cells markedly changes the proteoglycanome. The glycosaminoglycan biosynthetic pathway is complex and highly regulated, and therefore, understanding the details of this pathway should enable better control with the aim of directing stem cell differentiation. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Mesodermal origin of median fin mesenchyme and tail muscle in amphibian larvae.

    Science.gov (United States)

    Taniguchi, Yuka; Kurth, Thomas; Medeiros, Daniel Meulemans; Tazaki, Akira; Ramm, Robert; Epperlein, Hans-Henning

    2015-06-18

    Mesenchyme is an embryonic precursor tissue that generates a range of structures in vertebrates including cartilage, bone, muscle, kidney, and the erythropoietic system. Mesenchyme originates from both mesoderm and the neural crest, an ectodermal cell population, via an epithelial to mesenchymal transition (EMT). Because ectodermal and mesodermal mesenchyme can form in close proximity and give rise to similar derivatives, the embryonic origin of many mesenchyme-derived tissues is still unclear. Recent work using genetic lineage tracing methods have upended classical ideas about the contributions of mesodermal mesenchyme and neural crest to particular structures. Using similar strategies in the Mexican axolotl (Ambystoma mexicanum), and the South African clawed toad (Xenopus laevis), we traced the origins of fin mesenchyme and tail muscle in amphibians. Here we present evidence that fin mesenchyme and striated tail muscle in both animals are derived solely from mesoderm and not from neural crest. In the context of recent work in zebrafish, our experiments suggest that trunk neural crest cells in the last common ancestor of tetrapods and ray-finned fish lacked the ability to form ectomesenchyme and its derivatives.

  20. Mapping the Pairwise Choices Leading from Pluripotency to Human Bone, Heart, and Other Mesoderm Cell Types.

    Science.gov (United States)

    Loh, Kyle M; Chen, Angela; Koh, Pang Wei; Deng, Tianda Z; Sinha, Rahul; Tsai, Jonathan M; Barkal, Amira A; Shen, Kimberle Y; Jain, Rajan; Morganti, Rachel M; Shyh-Chang, Ng; Fernhoff, Nathaniel B; George, Benson M; Wernig, Gerlinde; Salomon, Rachel E A; Chen, Zhenghao; Vogel, Hannes; Epstein, Jonathan A; Kundaje, Anshul; Talbot, William S; Beachy, Philip A; Ang, Lay Teng; Weissman, Irving L

    2016-07-14

    Stem-cell differentiation to desired lineages requires navigating alternating developmental paths that often lead to unwanted cell types. Hence, comprehensive developmental roadmaps are crucial to channel stem-cell differentiation toward desired fates. To this end, here, we map bifurcating lineage choices leading from pluripotency to 12 human mesodermal lineages, including bone, muscle, and heart. We defined the extrinsic signals controlling each binary lineage decision, enabling us to logically block differentiation toward unwanted fates and rapidly steer pluripotent stem cells toward 80%-99% pure human mesodermal lineages at most branchpoints. This strategy enabled the generation of human bone and heart progenitors that could engraft in respective in vivo models. Mapping stepwise chromatin and single-cell gene expression changes in mesoderm development uncovered somite segmentation, a previously unobservable human embryonic event transiently marked by HOPX expression. Collectively, this roadmap enables navigation of mesodermal development to produce transplantable human tissue progenitors and uncover developmental processes. VIDEO ABSTRACT. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Boundaries and functional domains in the animal/vegetal axis of Xenopus gastrula mesoderm.

    Science.gov (United States)

    Kumano, G; Ezal, C; Smith, W C

    2001-08-15

    Patterning of the Xenopus gastrula marginal zone in the axis running equatorially from the Spemann organizer-the so--called "dorsal/ventral axis"--has been extensively studied. It is now evident that patterning in the animal/vegetal axis also needs to be taken into consideration. We have shown that an animal/vegetal pattern is apparent in the marginal zone by midgastrulation in the polarized expression domains of Xenopus brachyury (Xbra) and Xenopus nodal-related factor 2 (Xnr2). In this report, we have followed cells expressing Xbra in the presumptive trunk and tail at the gastrula stage, and find that they fate to presumptive somite, but not to ventrolateral mesoderm of the tailbud embryo. From this, we speculate that the boundary between the Xbra- and Xnr2-expressing cells at gastrula corresponds to a future tissue boundary. In further experiments, we show that the level of mitogen-activated protein kinase (MAPK) activation is polarized along the animal/vegetal axis, with the Xnr2-expressing cells in the vegetal marginal zone having no detectable activated MAPK. We show that inhibition of MAPK activation in Xenopus animal caps results in the conversion of Xnr2 from a dorsal mesoderm inducer to a ventral mesoderm inducer, supporting a role for Xnr2 in induction of ventral mesoderm. Copyright 2001 Academic Press.

  2. STRIP1, a core component of STRIPAK complexes, is essential for normal mesoderm migration in the mouse embryo.

    Science.gov (United States)

    Bazzi, Hisham; Soroka, Ekaterina; Alcorn, Heather L; Anderson, Kathryn V

    2017-12-19

    Regulated mesoderm migration is necessary for the proper morphogenesis and organ formation during embryonic development. Cell migration and its dependence on the cytoskeleton and signaling machines have been studied extensively in cultured cells; in contrast, remarkably little is known about the mechanisms that regulate mesoderm cell migration in vivo. Here, we report the identification and characterization of a mouse mutation in striatin-interacting protein 1 ( Strip1 ) that disrupts migration of the mesoderm after the gastrulation epithelial-to-mesenchymal transition (EMT). STRIP1 is a core component of the biochemically defined mammalian striatin-interacting phosphatases and kinase (STRIPAK) complexes that appear to act through regulation of protein phosphatase 2A (PP2A), but their functions in mammals in vivo have not been examined. Strip1 -null mutants arrest development at midgestation with profound disruptions in the organization of the mesoderm and its derivatives, including a complete failure of the anterior extension of axial mesoderm. Analysis of cultured mesoderm explants and mouse embryonic fibroblasts from null mutants shows that the mesoderm migration defect is correlated with decreased cell spreading, abnormal focal adhesions, changes in the organization of the actin cytoskeleton, and decreased velocity of cell migration. The results show that STRIPAK complexes are essential for cell migration and tissue morphogenesis in vivo. Copyright © 2017 the Author(s). Published by PNAS.

  3. Progenitors of secondary crest myofibroblasts are developmentally committed in early lung mesoderm.

    Science.gov (United States)

    Li, Changgong; Li, Min; Li, Sha; Xing, Yiming; Yang, Chang-Yo; Li, Aimin; Borok, Zea; De Langhe, Stijn; Minoo, Parviz

    2015-03-01

    Development of the mammalian lung is predicated on cross-communications between two highly interactive tissues, the endodermally derived epithelium and the mesodermally derived pulmonary mesenchyme. While much attention has been paid for the lung epithelium, the pulmonary mesenchyme, partly due to lack of specific tractable markers remains under-investigated. The lung mesenchyme is derived from the lateral plate mesoderm and is the principal recipient of Hedgehog (Hh) signaling, a morphogenetic network that regulates multiple aspects of embryonic development. Using the Hh-responsive Gli1-cre(ERT2) mouse line, we identified the mesodermal targets of Hh signaling at various time points during embryonic and postnatal lung development. Cell lineage analysis showed these cells serve as progenitors to contribute to multiple lineages of mesodermally derived differentiated cell types that include parenchymal or interstitial myofibroblasts, peribronchial and perivascular smooth muscle as well as rare populations of cells within the mesothelium. Most importantly, Gli1-cre(ERT2) identified the progenitors of secondary crest myofibroblasts, a hitherto intractable cell type that plays a key role in alveolar formation, a vital process about which little is currently known. Transcriptome analysis of Hh-targeted progenitor cells transitioning from the pseudoglandular to the saccular phase of lung development revealed important modulations of key signaling pathways. Among these, there was significant downregulation of canonical WNT signaling. Ectopic stabilization of β-catenin via inactivation of Apc by Gli1-cre(ERT2) expanded the Hh-targeted progenitor pools, which caused the formation of fibroblastic masses within the lung parenchyma. The Gli1-cre(ERT2) mouse line represents a novel tool in the analysis of mesenchymal cell biology and alveolar formation during lung development. © 2014 AlphaMed Press.

  4. The mesodermal expression of rolling stone (rost) is essential for myoblast fusion in Drosophila and encodes a potential transmembrane protein.

    Science.gov (United States)

    Paululat, A; Goubeaud, A; Damm, C; Knirr, S; Burchard, S; Renkawitz-Pohl, R

    1997-07-28

    In homozygous rolling stone embryos, the fusion of myoblasts to syncytial myotubes is diminished. Nevertheless, the visceral mesoderm, the heart mesoderm, and few somatic muscles are properly formed. Thus, we postulate a central role of rolling stone for the fusion process within the somatic mesoderm. We have cloned the rolling stone gene, and the deduced protein sequence is in accordance with a transmembrane protein, which agrees with the enrichment of Rost in the membrane fraction of Drosophila embryos. No homologous genes have been described so far. rolling stone is expressed in the embryonic nervous system and cells of the somatic mesoderm, most notable in muscle founder cells. To elucidate the function of rolling stone for myoblast fusion, we applied a knock-out strategy. The expression of an antisense rolling stone transcript specifically within the mesoderm of wild-type embryos results in fusion defects of myoblasts, proving that the rolling stone expression in the mesoderm is responsible for the rolling stone phenotype. We suggest that rolling stone is a member of a group of genes that are necessary for the fusion process during myogenesis.

  5. Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm

    Directory of Open Access Journals (Sweden)

    Avinash Waghray

    2015-07-01

    Full Text Available Tbx3, a member of the T-box family, plays important roles in development, stem cells, nuclear reprogramming, and cancer. Loss of Tbx3 induces differentiation in mouse embryonic stem cells (mESCs. However, we show that mESCs exist in an alternate stable pluripotent state in the absence of Tbx3. In-depth transcriptome analysis of this mESC state reveals Dppa3 as a direct downstream target of Tbx3. Also, Tbx3 facilitates the cell fate transition from pluripotent cells to mesoderm progenitors by directly repressing Wnt pathway members required for differentiation. Wnt signaling regulates differentiation of mESCs into mesoderm progenitors and helps to maintain a naive pluripotent state. We show that Tbx3, a downstream target of Wnt signaling, fine tunes these divergent roles of Wnt signaling in mESCs. In conclusion, we identify a signaling-TF axis that controls the exit of mESCs from a self-renewing pluripotent state toward mesoderm differentiation.

  6. Stochastic specification of primordial germ cells from mesoderm precursors in axolotl embryos.

    Science.gov (United States)

    Chatfield, Jodie; O'Reilly, Marie-Anne; Bachvarova, Rosemary F; Ferjentsik, Zoltan; Redwood, Catherine; Walmsley, Maggie; Patient, Roger; Loose, Mathew; Johnson, Andrew D

    2014-06-01

    A common feature of development in most vertebrate models is the early segregation of the germ line from the soma. For example, in Xenopus and zebrafish embryos primordial germ cells (PGCs) are specified by germ plasm that is inherited from the egg; in mice, Blimp1 expression in the epiblast mediates the commitment of cells to the germ line. How these disparate mechanisms of PGC specification evolved is unknown. Here, in order to identify the ancestral mechanism of PGC specification in vertebrates, we studied PGC specification in embryos from the axolotl (Mexican salamander), a model for the tetrapod ancestor. In the axolotl, PGCs develop within mesoderm, and classic studies have reported their induction from primitive ectoderm (animal cap). We used an axolotl animal cap system to demonstrate that signalling through FGF and BMP4 induces PGCs. The role of FGF was then confirmed in vivo. We also showed PGC induction by Brachyury, in the presence of BMP4. These conditions induced pluripotent mesodermal precursors that give rise to a variety of somatic cell types, in addition to PGCs. Irreversible restriction of the germ line did not occur until the mid-tailbud stage, days after the somatic germ layers are established. Before this, germline potential was maintained by MAP kinase signalling. We propose that this stochastic mechanism of PGC specification, from mesodermal precursors, is conserved in vertebrates. © 2014. Published by The Company of Biologists Ltd.

  7. Specification of Drosophila corpora cardiaca neuroendocrine cells from mesoderm is regulated by Notch signaling.

    Directory of Open Access Journals (Sweden)

    Sangbin Park

    2011-08-01

    Full Text Available Drosophila neuroendocrine cells comprising the corpora cardiaca (CC are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells. Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland, the genetic regulation of CC development is poorly understood. From a genetic screen, we identified multiple novel regulators of CC development, including Notch signaling factors. Our studies demonstrate that the disruption of Notch signaling can lead to the expansion of CC cells. Live imaging demonstrates localized emergence of extra precursor cells as the basis of CC expansion in Notch mutants. Contrary to a recent report, we unexpectedly found that CC cells originate from head mesoderm. We show that Tinman expression in head mesoderm is regulated by Notch signaling and that the combination of Daughterless and Tinman is sufficient for ectopic CC specification in mesoderm. Understanding the cellular, genetic, signaling, and transcriptional basis of CC cell specification and expansion should accelerate discovery of molecular mechanisms regulating ontogeny of organs that control metabolism.

  8. Mesoderm Lineage 3D Tissue Constructs Are Produced at Large-Scale in a 3D Stem Cell Bioprocess.

    Science.gov (United States)

    Cha, Jae Min; Mantalaris, Athanasios; Jung, Sunyoung; Ji, Yurim; Bang, Oh Young; Bae, Hojae

    2017-09-01

    Various studies have presented different approaches to direct pluripotent stem cell differentiation such as applying defined sets of exogenous biochemical signals and genetic/epigenetic modifications. Although differentiation to target lineages can be successfully regulated, such conventional methods are often complicated, laborious, and not cost-effective to be employed to the large-scale production of 3D stem cell-based tissue constructs. A 3D-culture platform that could realize the large-scale production of mesoderm lineage tissue constructs from embryonic stem cells (ESCs) is developed. ESCs are cultured using our previously established 3D-bioprocess platform which is amenable to mass-production of 3D ESC-based tissue constructs. Hepatocarcinoma cell line conditioned medium is introduced to the large-scale 3D culture to provide a specific biomolecular microenvironment to mimic in vivo mesoderm formation process. After 5 days of spontaneous differentiation period, the resulting 3D tissue constructs are composed of multipotent mesodermal progenitor cells verified by gene and molecular expression profiles. Subsequently the optimal time points to trigger terminal differentiation towards cardiomyogenesis or osteogenesis from the mesodermal tissue constructs is found. A simple and affordable 3D ESC-bioprocess that can reach the scalable production of mesoderm origin tissues with significantly improved correspondent tissue properties is demonstrated. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm

    Science.gov (United States)

    Rossi, Jennifer M.; Dunn, N. Ray; Hogan, Brigid L.M.; Zaret, Kenneth S.

    2001-01-01

    Mesodermal signaling is critical for patterning the embryonic endoderm into different tissue domains. Classical tissue transplant experiments in the chick and recent studies in the mouse indicated that interactions with the cardiogenic mesoderm are necessary and sufficient to induce the liver in the ventral foregut endoderm. Using molecular markers and functional assays, we now show that septum transversum mesenchyme cells, a distinct mesoderm cell type, are closely apposed to the ventral endoderm and contribute to hepatic induction. Specifically, using a mouse Bmp4 null mutation and an inhibitor of BMPs, we find that BMP signaling from the septum transversum mesenchyme is necessary to induce liver genes in the endoderm and to exclude a pancreatic fate. BMPs apparently function, in part, by affecting the levels of the GATA4 transcription factor, and work in parallel to FGF signaling from the cardiac mesoderm. BMP signaling also appears critical for morphogenetic growth of the hepatic endoderm into a liver bud. Thus, the endodermal domain for the liver is specified by simultaneous signaling from distinct mesodermal sources. PMID:11485993

  10. TET2 deficiency inhibits mesoderm and hematopoietic differentiation in human embryonic stem cells

    DEFF Research Database (Denmark)

    Langlois, Thierry; da Costa Reis Monte Mor, Barbara; Lenglet, Gaëlle

    2014-01-01

    . Here, we show that TET2 expression is low in human embryonic stem (ES) cell lines and increases during hematopoietic differentiation. ShRNA-mediated TET2 knockdown had no effect on the pluripotency of various ES cells. However, it skewed their differentiation into neuroectoderm at the expense...... profile, including abnormal expression of neuronal genes. Intriguingly, when TET2 was knockdown in hematopoietic cells, it increased hematopoietic development. In conclusion, our work suggests that TET2 is involved in different stages of human embryonic development, including induction of the mesoderm...... and hematopoietic differentiation. Stem Cells 2014....

  11. Transcriptional targets of TWIST1 in the cranial mesoderm regulate cell-matrix interactions and mesenchyme maintenance.

    Science.gov (United States)

    Bildsoe, Heidi; Fan, Xiaochen; Wilkie, Emilie E; Ashoti, Ator; Jones, Vanessa J; Power, Melinda; Qin, Jing; Wang, Junwen; Tam, Patrick P L; Loebel, David A F

    2016-10-01

    TWIST1, a basic helix-loop-helix transcription factor is essential for the development of cranial mesoderm and cranial neural crest-derived craniofacial structures. We have previously shown that, in the absence of TWIST1, cells within the cranial mesoderm adopt an abnormal epithelial configuration via a process reminiscent of a mesenchymal to epithelial transition (MET). Here, we show by gene expression analysis that loss of TWIST1 in the cranial mesoderm is accompanied by a reduction in the expression of genes that are associated with cell-extracellular matrix interactions and the acquisition of mesenchymal characteristics. By comparing the transcriptional profiles of cranial mesoderm-specific Twist1 loss-of-function mutant and control mouse embryos, we identified a set of genes that are both TWIST1-dependent and predominantly expressed in the mesoderm. ChIP-seq was used to identify TWIST1-binding sites in an in vitro model of a TWIST1-dependent mesenchymal cell state, and the data were combined with the transcriptome data to identify potential target genes. Three direct transcriptional targets of TWIST1 (Ddr2, Pcolce and Tgfbi) were validated by ChIP-PCR using mouse embryonic tissues and by luciferase assays. Our findings reveal that the mesenchymal properties of the cranial mesoderm are likely to be regulated by a network of TWIST1 targets that influences the extracellular matrix and cell-matrix interactions, and collectively they are required for the morphogenesis of the craniofacial structures. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. A study of mesoderm patterning through the analysis of the regulation of Xmyf-5 expression.

    Science.gov (United States)

    Polli, Matthew; Amaya, Enrique

    2002-06-01

    Xenopus laevis has been a particularly useful model organism for identifying factors involved in the induction and patterning of the mesoderm, however, much remains to be learned about how these factors interact. The myogenic transcription factor Xmyf-5 is the earliest known gene to be expressed specifically in the dorsolateral mesoderm of the gastrula, a domain that is established by the interaction of dorsal and ventral signals. For this reason, we have begun to investigate how the expression of Xmyf-5 is regulated. We have identified a 7.28 kb Xenopus tropicalis Xmyf-5 (Xtmyf-5) genomic DNA fragment that accurately recapitulates the expression of the endogenous gene. Deletion and mutational analysis has identified HBX2, an essential element, approximately 1.2 kb upstream from the start of transcription, which is necessary for both activation and repression of Xtmyf-5 expression, implying that positional information is integrated at this site. Electrophoretic mobility shift assays demonstrate that HBX2 specifically interacts with gastrula stage embryonic extracts and that in vitro translated Xvent-1 protein binds to one of its functional motifs. Combined with gain- and loss-of-function experiments, the promoter analysis described here suggests that Xvent-1 functions to repress Xmyf-5 expression in the ventral domain of the marginal zone. Furthermore, the identification of HBX2 provides a tool with which to identify other molecules involved in the regulation of Xmyf-5 expression during gastrulation.

  13. Xenopus Sprouty2 inhibits FGF-mediated gastrulation movements but does not affect mesoderm induction and patterning

    Science.gov (United States)

    Nutt, Stephen L.; Dingwell, Kevin S.; Holt, Christine E.; Amaya, Enrique

    2001-01-01

    Signal transduction through the FGF receptor is essential for the specification of the vertebrate body plan. Blocking the FGF pathway in early Xenopus embryos inhibits mesoderm induction and results in truncation of the anterior–posterior axis. The Drosophila gene sprouty encodes an antagonist of FGF signaling, which is transcriptionally induced by the pathway, but whose molecular functions are poorly characterized. We have cloned Xenopus sprouty2 and show that it is expressed in a similar pattern to known FGFs and is dependent on the FGF/Ras/MAPK pathway for its expression. Overexpression of Xsprouty2 in both embryos and explant assays results in the inhibition of the cell movements of convergent extension. Although blocking FGF/Ras/MAPK signaling leads to an inhibition of mesodermal gene expression, these markers are unaffected by Xsprouty2, indicating that mesoderm induction and patterning occurs normally in these embryos. Finally, using Xenopus oocytes we show that Xsprouty2 is an intracellular antagonist of FGF-dependent calcium signaling. These results provide evidence for at least two distinct FGF-dependent signal transduction pathways: a Sprouty-insensitive Ras/MAPK pathway required for the transcription of most mesodermal genes, and a Sprouty-sensitive pathway required for coordination of cellular morphogenesis. PMID:11331610

  14. Genetic ablation of FLRT3 reveals a novel morphogenetic function for the anterior visceral endoderm in suppressing mesoderm differentiation.

    Science.gov (United States)

    Egea, Joaquim; Erlacher, Christian; Montanez, Eloi; Burtscher, Ingo; Yamagishi, Satoru; Hess, Martin; Hampel, Falko; Sanchez, Rodrigo; Rodriguez-Manzaneque, Maria Teresa; Bösl, Michael R; Fässler, Reinhard; Lickert, Heiko; Klein, Rüdiger

    2008-12-01

    During early mouse development, the anterior visceral endoderm (AVE) secretes inhibitor and activator signals that are essential for establishing the anterior-posterior (AP) axis of the embryo and for restricting mesoderm formation to the posterior epiblast in the primitive streak (PS) region. Here we show that AVE cells have an additional morphogenetic function. These cells express the transmembrane protein FLRT3. Genetic ablation of FLRT3 did not affect the signaling functions of the AVE according to the normal expression pattern of Nodal and Wnt and the establishment of a proper AP patterning in the epiblast. However, FLRT3(-/-) embryos showed a highly disorganized basement membrane (BM) in the AVE region. Subsequently, adjacent anterior epiblast cells displayed an epithelial-to-mesenchymal transition (EMT)-like process characterized by the loss of cell polarity, cell ingression, and the up-regulation of the EMT and the mesodermal marker genes Eomes, Brachyury/T, and FGF8. These results suggest that the AVE acts as a morphogenetic boundary to prevent EMT and mesoderm induction in the anterior epiblast by maintaining the integrity of the BM. We propose that this novel function cooperates with the signaling activities of the AVE to restrict EMT and mesoderm induction to the posterior epiblast.

  15. POS-1 promotes endo-mesoderm development by inhibiting the cytoplasmic polyadenylation of neg-1 mRNA

    Science.gov (United States)

    Elewa, Ahmed; Shirayama, Masaki; Kaymak, Ebru; Harrison, Paul F.; Powell, David R.; Du, Zhuo; Chute, Christopher D.; Woolf, Hannah; Yi, Dongni; Ishidate, Takao; Srinivasan, Jagan; Bao, Zhirong; Beilharz, Traude H.; Ryder, Sean; Mello, Craig C.

    2015-01-01

    SUMMARY The regulation of mRNA translation is of fundamental importance in biological mechanisms ranging from embryonic axis specification to formation of long-term memory. POS-1 is one of several CCCH zinc-finger RNA-binding proteins that regulate cell-fate specification during C. elegans embryogenesis. Paradoxically, pos-1 mutants exhibit striking defects in endo-mesoderm development, but have wildtype distributions of SKN-1, a key determinant of endo-mesoderm fates. RNAi screens for pos-1 suppressors identified genes encoding the cytoplasmic poly(A)-polymerase homolog GLD-2, the Bicaudal-C homolog GLD-3, and the protein NEG-1. We show that NEG-1 localizes in anterior nuclei where it negatively regulates endo-mesoderm fates. In posterior cells, POS-1 binds the neg-1 3′UTR to oppose GLD-2 and GLD-3 activities that promote NEG-1 expression and cytoplasmic lengthening of the neg-1 mRNA poly(A) tail. Our findings uncover an intricate series of post-transcriptional regulatory interactions that together achieve precise spatial expression of endo-mesoderm fates in C. elegans embryos. PMID:26096734

  16. p38 mitogen activated protein kinase controls two successive-steps during the early mesodermal commitment of embryonic stem cells.

    Science.gov (United States)

    Barruet, Emilie; Hadadeh, Ola; Peiretti, Franck; Renault, Valérie M; Hadjal, Yasmine; Bernot, Denis; Tournaire, Roselyne; Negre, Didier; Juhan-Vague, Irène; Alessi, Marie-Christine; Binétruy, Bernard

    2011-07-01

    Embryonic stem (ES) cells differentiate in vitro into all cell lineages. We previously found that the p38 mitogen activated kinase (p38MAPK) pathway controls the commitment of ES cells toward either cardiomyogenesis (p38 on) or neurogenesis (p38 off ). In this study, we show that p38α knock-out ES cells do not differentiate into cardiac, endothelial, smooth muscle, and skeletal muscle lineages. Reexpression of p38MAPK in these cells partially rescues their mesodermal differentiation defects and corrects the high level of spontaneous neurogenesis of knock-out cells. Wild-type ES cells were treated with a p38MAPK-specific inhibitor during the differentiation process. These experiments allowed us to identify 2 early independent successive p38MAPK functions in the formation of mesodermal lineages. Further, the first one correlates with the regulation of the expression of Brachyury, an essential mesodermal-specific transcription factor, by p38MAPK. In conclusion, by genetic and biochemical approaches, we demonstrate that p38MAPK activity is essential for the commitment of ES cell into cardiac, endothelial, smooth muscle, and skeletal muscle mesodermal lineages.

  17. The nodal target gene Xmenf is a component of an FGF-independent pathway of ventral mesoderm induction in Xenopus.

    Science.gov (United States)

    Kumano, Gaku; Smith, William C

    2002-10-01

    The interplay of fibroblast growth factor (FGF) and nodal signaling in the Xenopus gastrula marginal zone specifies distinct populations of presumptive mesodermal cells. Cells in the vegetal marginal zone, making up the presumptive leading edge mesoderm, are exposed to nodal signaling, as evidenced by SMAD2 activation, but do not appear to be exposed to FGF signaling, as evidenced by the lack of MAP kinase (MAPK) activation. However, in the animal marginal zone, activation of both SMAD2 and MAPK occurs. The differential activation of these two signaling pathways in the marginal zone results in the vegetal and animal marginal zones expressing different genes at gastrulation, and subsequently having different fates, with the vegetal marginal zone contributing to ventral mesoderm (e.g. ventral blood island) and the animal marginal zone giving rise to dorsal fates (e.g. notochord and somite). We report here the cloning of a cDNA encoding a novel nuclear protein, Xmenf, that is expressed in the vegetal marginal zone. The expression of Xmenf is induced by nodal signaling and negatively regulated by FGF signaling. Results from animal cap studies indicate that Xmenf plays a role in the pathway of ventral mesoderm induction in the vegetal marginal zone.

  18. The chick somitogenesis oscillator is arrested before all paraxial mesoderm is segmented into somites

    Directory of Open Access Journals (Sweden)

    McGrew Michael J

    2010-02-01

    Full Text Available Abstract Background Somitogenesis is the earliest sign of segmentation in the developing vertebrate embryo. This process starts very early, soon after gastrulation has initiated and proceeds in an anterior-to-posterior direction during body axis elongation. It is widely accepted that somitogenesis is controlled by a molecular oscillator with the same periodicity as somite formation. This periodic mechanism is repeated a specific number of times until the embryo acquires a defined specie-specific final number of somites at the end of the process of axis elongation. This final number of somites varies widely between vertebrate species. How termination of the process of somitogenesis is determined is still unknown. Results Here we show that during development there is an imbalance between the speed of somite formation and growth of the presomitic mesoderm (PSM/tail bud. This decrease in the PSM size of the chick embryo is not due to an acceleration of the speed of somite formation because it remains constant until the last stages of somitogenesis, when it slows down. When the chick embryo reaches its final number of somites at stage HH 24-25 there is still some remaining unsegmented PSM in which expression of components of the somitogenesis oscillator is no longer dynamic. Finally, we identify a change in expression of retinoic acid regulating factors in the tail bud at late stages of somitogenesis, such that in the chick embryo there is a pronounced onset of Raldh2 expression while in the mouse embryo the expression of the RA inhibitor Cyp26A1 is downregulated. Conclusions Our results show that the chick somitogenesis oscillator is arrested before all paraxial mesoderm is segmented into somites. In addition, endogenous retinoic acid is probably also involved in the termination of the process of segmentation, and in tail growth in general.

  19. Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.

    Science.gov (United States)

    Lojewski, Xenia; Srimasorn, Sumitra; Rauh, Juliane; Francke, Silvan; Wobus, Manja; Taylor, Verdon; Araúzo-Bravo, Marcos J; Hallmeyer-Elgner, Susanne; Kirsch, Matthias; Schwarz, Sigrid; Schwarz, Johannes; Storch, Alexander; Hermann, Andreas

    2015-10-01

    Brain perivascular cells have recently been identified as a novel mesodermal cell type in the human brain. These cells reside in the perivascular niche and were shown to have mesodermal and, to a lesser extent, tissue-specific differentiation potential. Mesenchymal stem cells (MSCs) are widely proposed for use in cell therapy in many neurological disorders; therefore, it is of importance to better understand the "intrinsic" MSC population of the human brain. We systematically characterized adult human brain-derived pericytes during in vitro expansion and differentiation and compared these cells with fetal and adult human brain-derived neural stem cells (NSCs) and adult human bone marrow-derived MSCs. We found that adult human brain pericytes, which can be isolated from the hippocampus and from subcortical white matter, are-in contrast to adult human NSCs-easily expandable in monolayer cultures and show many similarities to human bone marrow-derived MSCs both regarding both surface marker expression and after whole transcriptome profile. Human brain pericytes showed a negligible propensity for neuroectodermal differentiation under various differentiation conditions but efficiently generated mesodermal progeny. Consequently, human brain pericytes resemble bone marrow-derived MSCs and might be very interesting for possible autologous and endogenous stem cell-based treatment strategies and cell therapeutic approaches for treating neurological diseases. Perivascular mesenchymal stem cells (MSCs) recently gained significant interest because of their appearance in many tissues including the human brain. MSCs were often reported as being beneficial after transplantation in the central nervous system in different neurological diseases; therefore, adult brain perivascular cells derived from human neural tissue were systematically characterized concerning neural stem cell and MSC marker expression, transcriptomics, and mesodermal and inherent neuroectodermal differentiation

  20. Knockout of the PKN Family of Rho Effector Kinases Reveals a Non-redundant Role for PKN2 in Developmental Mesoderm Expansion

    Directory of Open Access Journals (Sweden)

    Ivan Quétier

    2016-01-01

    Full Text Available In animals, the protein kinase C (PKC family has expanded into diversely regulated subgroups, including the Rho family-responsive PKN kinases. Here, we describe knockouts of all three mouse PKN isoforms and reveal that PKN2 loss results in lethality at embryonic day 10 (E10, with associated cardiovascular and morphogenetic defects. The cardiovascular phenotype was not recapitulated by conditional deletion of PKN2 in endothelial cells or the developing heart. In contrast, inducible systemic deletion of PKN2 after E7 provoked collapse of the embryonic mesoderm. Furthermore, mouse embryonic fibroblasts, which arise from the embryonic mesoderm, depend on PKN2 for proliferation and motility. These cellular defects are reflected in vivo as dependence on PKN2 for mesoderm proliferation and neural crest migration. We conclude that failure of the mesoderm to expand in the absence of PKN2 compromises cardiovascular integrity and development, resulting in lethality.

  1. Development of the lateral plate mesoderm in medaka Oryzias latipes and Nile tilapia Oreochromis niloticus: insight into the diversification of pelvic fin position

    Science.gov (United States)

    Kaneko, Hiroki; Nakatani, Yuki; Fujimura, Koji; Tanaka, Mikiko

    2014-01-01

    The position of the pelvic fins among teleost fishes has tended to shift rostrally during evolution. This positional shift seems to have led to the diversification of feeding behavior and allowed adaptation to new environments. To understand the developmental basis of this shift in pelvic fin position among teleosts, we investigated the embryonic development of the lateral plate mesoderm, which gives rise to the pelvic fins, at histological levels in the medaka Oryzias latipes (abdominal pelvic fins) and Nile tilapia Oreochromis niloticus (thoracic pelvic fins). Our histological analyses revealed that the lateral plate mesodermal cells expand not only ventrally but also rostrally to cover the yolk during embryogenesis of both medaka and Nile tilapia. In medaka, we also found that the lateral plate mesoderm completely covered the yolk prior to the initiation of the pelvic fin buds, whereas in Nile tilapia the pelvic fin buds appeared in the body wall from the lateral plate mesoderm at the thoracic level when the lateral plate mesodermal cells only covered one-third of the yolk. We discuss the relevance of such differences in the rate of the lateral plate mesoderm expansion on the yolk surface and the position of the pelvic fins. PMID:25345789

  2. FGF and canonical Wnt signaling cooperate to induce paraxial mesoderm from tailbud neuromesodermal progenitors through regulation of a two-step epithelial to mesenchymal transition.

    Science.gov (United States)

    Goto, Hana; Kimmey, Samuel C; Row, Richard H; Matus, David Q; Martin, Benjamin L

    2017-04-15

    Mesoderm induction begins during gastrulation. Recent evidence from several vertebrate species indicates that mesoderm induction continues after gastrulation in neuromesodermal progenitors (NMPs) within the posteriormost embryonic structure, the tailbud. It is unclear to what extent the molecular mechanisms of mesoderm induction are conserved between gastrula and post-gastrula stages of development. Fibroblast growth factor (FGF) signaling is required for mesoderm induction during gastrulation through positive transcriptional regulation of the T-box transcription factor brachyury We find in zebrafish that FGF is continuously required for paraxial mesoderm (PM) induction in post-gastrula NMPs. FGF signaling represses the NMP markers brachyury ( ntla ) and sox2 through regulation of tbx16 and msgn1 , thereby committing cells to a PM fate. FGF-mediated PM induction in NMPs functions in tight coordination with canonical Wnt signaling during the epithelial to mesenchymal transition (EMT) from NMP to mesodermal progenitor. Wnt signaling initiates EMT, whereas FGF signaling terminates this event. Our results indicate that germ layer induction in the zebrafish tailbud is not a simple continuation of gastrulation events. © 2017. Published by The Company of Biologists Ltd.

  3. NSrp70 is significant for embryonic growth and development, being a crucial factor for gastrulation and mesoderm induction.

    Science.gov (United States)

    Lee, Soo-Ho; Kim, Chowon; Lee, Hyun-Kyung; Kim, Yoo-Kyung; Ismail, Tayaba; Jeong, Youngeun; Park, Kyungyeon; Park, Mae-Ja; Park, Do-Sim; Lee, Hyun-Shik

    2016-10-14

    NSrp70 (nuclear speckle-related protein 70), a recently discovered protein and it belongs to the serine/arginine (SR) rich related protein family. NSrp70 is recognized as an important splicing factor comprising RNA recognition motif (RRM) and arginine/serine (RS)-like regions at the N- and C-terminus respectively, along with two coiled coil domains at each terminus. However, other functions of NSrp70 remain unelucidated. In this study, we investigated the role of NSrp70 in Xenopus embryogenesis and found that its maternal expression plays a critical role in embryonic development. Knockdown of NSrp70 resulted in dramatic reduction in the length of developing tadpoles and mild to severe malformation in Xenopus embryos. In addition, knockdown of NSrp70 resulted in an extremely short axis by blocking gastrulation and convergent extension. Further, animal cap assays along with activin A treatment revealed that NSrp70 is an essential factor for dorsal mesoderm induction as knockdown of NSrp70 caused a dramatic down-regulation of dorsal mesoderm specific genes and its loss significantly shortened the elongation region of animal caps. In conclusion, NSrp70 is crucial for early embryonic development, influencing gastrulation and mesoderm induction. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Delayed Mesoderm and Erythroid Differentiation of Murine Embryonic Stem Cells in the Absence of the Transcriptional Regulator FUBP1

    Directory of Open Access Journals (Sweden)

    Josephine Wesely

    2017-01-01

    Full Text Available The transcriptional regulator far upstream binding protein 1 (FUBP1 is essential for fetal and adult hematopoietic stem cell (HSC self-renewal, and the constitutive absence of FUBP1 activity during early development leads to embryonic lethality in homozygous mutant mice. To investigate the role of FUBP1 in murine embryonic stem cells (ESCs and in particular during differentiation into hematopoietic lineages, we generated Fubp1 knockout (KO ESC clones using CRISPR/Cas9 technology. Although FUBP1 is expressed in undifferentiated ESCs and during spontaneous differentiation following aggregation into embryoid bodies (EBs, absence of FUBP1 did not affect ESC maintenance. Interestingly, we observed a delayed differentiation of FUBP1-deficient ESCs into the mesoderm germ layer, as indicated by impaired expression of several mesoderm markers including Brachyury at an early time point of ESC differentiation upon aggregation to EBs. Coculture experiments with OP9 cells in the presence of erythropoietin revealed a diminished differentiation capacity of Fubp1 KO ESCs into the erythroid lineage. Our data showed that FUBP1 is important for the onset of mesoderm differentiation and maturation of hematopoietic progenitor cells into the erythroid lineage, a finding that is supported by the phenotype of FUBP1-deficient mice.

  5. Mesodermal iPSC–derived progenitor cells functionally regenerate cardiac and skeletal muscle

    Science.gov (United States)

    Quattrocelli, Mattia; Swinnen, Melissa; Giacomazzi, Giorgia; Camps, Jordi; Barthélemy, Ines; Ceccarelli, Gabriele; Caluwé, Ellen; Grosemans, Hanne; Thorrez, Lieven; Pelizzo, Gloria; Muijtjens, Manja; Verfaillie, Catherine M.; Blot, Stephane; Janssens, Stefan; Sampaolesi, Maurilio

    2015-01-01

    Conditions such as muscular dystrophies (MDs) that affect both cardiac and skeletal muscles would benefit from therapeutic strategies that enable regeneration of both of these striated muscle types. Protocols have been developed to promote induced pluripotent stem cells (iPSCs) to differentiate toward cardiac or skeletal muscle; however, there are currently no strategies to simultaneously target both muscle types. Tissues exhibit specific epigenetic alterations; therefore, source-related lineage biases have the potential to improve iPSC-driven multilineage differentiation. Here, we determined that differential myogenic propensity influences the commitment of isogenic iPSCs and a specifically isolated pool of mesodermal iPSC-derived progenitors (MiPs) toward the striated muscle lineages. Differential myogenic propensity did not influence pluripotency, but did selectively enhance chimerism of MiP-derived tissue in both fetal and adult skeletal muscle. When injected into dystrophic mice, MiPs engrafted and repaired both skeletal and cardiac muscle, reducing functional defects. Similarly, engraftment into dystrophic mice of canine MiPs from dystrophic dogs that had undergone TALEN-mediated correction of the MD-associated mutation also resulted in functional striatal muscle regeneration. Moreover, human MiPs exhibited the same capacity for the dual differentiation observed in murine and canine MiPs. The findings of this study suggest that MiPs should be further explored for combined therapy of cardiac and skeletal muscles. PMID:26571398

  6. Mesogenin 1 is a master regulator of paraxial presomitic mesoderm differentiation

    Science.gov (United States)

    Chalamalasetty, Ravindra B.; Garriock, Robert J.; Dunty, William C.; Kennedy, Mark W.; Jailwala, Parthav; Si, Han; Yamaguchi, Terry P.

    2014-01-01

    Neuromesodermal (NM) stem cells generate neural and paraxial presomitic mesoderm (PSM) cells, which are the respective progenitors of the spinal cord and musculoskeleton of the trunk and tail. The Wnt-regulated basic helix-loop-helix (bHLH) transcription factor mesogenin 1 (Msgn1) has been implicated as a cooperative regulator working in concert with T-box genes to control PSM formation in zebrafish, although the mechanism is unknown. We show here that, in mice, Msgn1 alone controls PSM differentiation by directly activating the transcriptional programs that define PSM identity, epithelial-mesenchymal transition, motility and segmentation. Forced expression of Msgn1 in NM stem cells in vivo reduced the contribution of their progeny to the neural tube, and dramatically expanded the unsegmented mesenchymal PSM while blocking somitogenesis and notochord differentiation. Expression of Msgn1 was sufficient to partially rescue PSM differentiation in Wnt3a−/− embryos, demonstrating that Msgn1 functions downstream of Wnt3a as the master regulator of PSM differentiation. Our data provide new insights into how cell fate decisions are imposed by the expression of a single transcriptional regulator. PMID:25371364

  7. Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages

    International Nuclear Information System (INIS)

    Caiazzo, Massimiliano; Colucci-D'Amato, Luca; Esposito, Maria T.; Parisi, Silvia; Stifani, Stefano; Ramirez, Francesco; Porzio, Umberto di

    2010-01-01

    Previous gene targeting studies in mice have implicated the nuclear protein Krueppel-like factor 7 (KLF7) in nervous system development while cell culture assays have documented its involvement in cell cycle regulation. By employing short hairpin RNA (shRNA)-mediated gene silencing, here we demonstrate that murine Klf7 gene expression is required for in vitro differentiation of neuroectodermal and mesodermal cells. Specifically, we show a correlation of Klf7 silencing with down-regulation of the neuronal marker microtubule-associated protein 2 (Map2) and the nerve growth factor (NGF) tyrosine kinase receptor A (TrkA) using the PC12 neuronal cell line. Similarly, KLF7 inactivation in Klf7-null mice decreases the expression of the neurogenic marker brain lipid-binding protein/fatty acid-binding protein 7 (BLBP/FABP7) in neural stem cells (NSCs). We also report that Klf7 silencing is detrimental to neuronal and cardiomyocytic differentiation of embryonic stem cells (ESCs), in addition to altering the adipogenic and osteogenic potential of mouse embryonic fibroblasts (MEFs). Finally, our results suggest that genes that are key for self-renewal of undifferentiated ESCs repress Klf7 expression in ESCs. Together with previous findings, these results provide evidence that KLF7 has a broad spectrum of regulatory functions, which reflect the discrete cellular and molecular contexts in which this transcription factor operates.

  8. Circulation-Independent Differentiation Pathway from Extraembryonic Mesoderm toward Hematopoietic Stem Cells via Hemogenic Angioblasts

    Directory of Open Access Journals (Sweden)

    Yosuke Tanaka

    2014-07-01

    Full Text Available A large gap exists in our understanding of the course of differentiation from mesoderm to definitive hematopoietic stem cells (HSCs. Previously, we reported that Runx1+ cells in embryonic day 7.5 (E7.5 embryos contribute to the hemogenic endothelium in the E10.5 aorta-gonad-mesonephros (AGM region and HSCs in the adult bone marrow. Here, we show that two Runx1+ populations subdivided by Gata1 expression exist in E7.5 embryos. The hemogenic endothelium and the HSCs are derived only from the Runx1+Gata1− population. A subset of this population moves from the extra- to intraembryonic region during E7.5–E8.0, where it contributes to the hemogenic endothelium of the dorsal aorta (DA. Migration occurs before the heartbeat is initiated, and it is independent of circulation. This suggests a developmental trajectory from Runx1+ cells in the E7.5 extraembryonic region to definitive HSCs via the hemogenic endothelium.

  9. Visualizing late insect embryogenesis: extraembryonic and mesodermal enhancer trap expression in the beetle Tribolium castaneum.

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    Stefan Koelzer

    Full Text Available The beetle Tribolium castaneum has increasingly become a powerful model for comparative research on insect development. One recent resource is a collection of piggyBac transposon-based enhancer trap lines. Here, we provide a detailed analysis of three selected lines and demonstrate their value for investigations in the second half of embryogenesis, which has thus far lagged behind research on early stages. Two lines, G12424 and KT650, show enhanced green fluorescent protein (EGFP expression throughout the extraembryonic serosal tissue and in a few discrete embryonic domains. Intriguingly, both lines show for the first time a degree of regionalization within the mature serosa. However, their expression profiles illuminate distinct aspects of serosal biology: G12424 tracks the tissue's rapid maturation while KT650 expression likely reflects ongoing physiological processes. The third line, G04609, is stably expressed in mesodermal domains, including segmental muscles and the heart. Genomic mapping followed by in situ hybridization for genes near to the G04609 insertion site suggests that the transposon has trapped enhancer information for the Tribolium orthologue of midline (Tc-mid. Altogether, our analyses provide the first live imaging, long-term characterizations of enhancer traps from this collection. We show that EGFP expression is readily detected, including in heterozygote crosses that permit the simultaneous visualization of multiple tissue types. The tissue specificity provides live, endogenous marker gene expression at key developmental stages that are inaccessible for whole mount staining. Furthermore, the nonlocalized EGFP in these lines illuminates both the nucleus and cytoplasm, providing cellular resolution for morphogenesis research on processes such as dorsal closure and heart formation. In future work, identification of regulatory regions driving these enhancer traps will deepen our understanding of late developmental control

  10. Mesoderm/mesenchyme homeobox gene l promotes vascular smooth muscle cell phenotypic modulation and vascular remodeling.

    Science.gov (United States)

    Wu, Bing; Zhang, Lei; Zhu, Yun-He; Zhang, You-En; Zheng, Fei; Yang, Jian-Ye; Guo, Ling-Yun; Li, Xing-Yuan; Wang, Lu; Tang, Jun-Ming; Chen, Shi-You; Wang, Jia-Ning

    2018-01-15

    To investigate the role of mesoderm/mesenchyme homeobox gene l (Meox1) in vascular smooth muscle cells (SMCs) phenotypic modulation during vascular remodeling. By using immunostaining, Western blot, and histological analyses, we found that Meox1 was up-regulated in PDGF-BB-treated SMCs in vitro and balloon injury-induced arterial SMCs in vivo. Meox1 knockdown by shRNA restored the expression of contractile SMCs phenotype markers including smooth muscle α-actin (α-SMA) and calponin. In contrast, overexpression of Moex1 inhibited α-SMA and calponin expressions while inducing the expressions of synthetic SMCs phenotype markers such as matrix gla protein, osteopontin, and proliferating cell nuclear antigen. Mechanistically, Meox1 mediated the SMCs phenotypic modulation through FAK-ERK1/2 signaling, which appears to induce autophagy in SMCs. In vivo, knockdown of Meox1 attenuated injury-induced neointima formation and promoted SMCs contractile proteins expressions. Meox1 knockdown also reduced the number of proliferating SMCs, suggesting that Meox1 was important for SMCs proliferation in vivo. Moreover, knockdown of Meox1 attenuated ERK1/2 signaling and autophagy markers expressions, suggesting that Meox1 may promote SMCs phenotypic modulation via ERK1/2 signaling-autophagy in vivo. Our data indicated that Meox1 promotes SMCs phenotypic modulation and injury-induced vascular remodeling by regulating the FAK-ERK1/2-autophagy signaling cascade. Thus, targeting Meox1 may be an attractive approach for treating proliferating vascular diseases. Copyright © 2017. Published by Elsevier B.V.

  11. From dynamic expression patterns to boundary formation in the presomitic mesoderm.

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    Hendrik B Tiedemann

    Full Text Available The segmentation of the vertebrate body is laid down during early embryogenesis. The formation of signaling gradients, the periodic expression of genes of the Notch-, Fgf- and Wnt-pathways and their interplay in the unsegmented presomitic mesoderm (PSM precedes the rhythmic budding of nascent somites at its anterior end, which later develops into epithelialized structures, the somites. Although many in silico models describing partial aspects of somitogenesis already exist, simulations of a complete causal chain from gene expression in the growth zone via the interaction of multiple cells to segmentation are rare. Here, we present an enhanced gene regulatory network (GRN for mice in a simulation program that models the growing PSM by many virtual cells and integrates WNT3A and FGF8 gradient formation, periodic gene expression and Delta/Notch signaling. Assuming Hes7 as core of the somitogenesis clock and LFNG as modulator, we postulate a negative feedback of HES7 on Dll1 leading to an oscillating Dll1 expression as seen in vivo. Furthermore, we are able to simulate the experimentally observed wave of activated NOTCH (NICD as a result of the interactions in the GRN. We esteem our model as robust for a wide range of parameter values with the Hes7 mRNA and protein decays exerting a strong influence on the core oscillator. Moreover, our model predicts interference between Hes1 and HES7 oscillators when their intrinsic frequencies differ. In conclusion, we have built a comprehensive model of somitogenesis with HES7 as core oscillator that is able to reproduce many experimentally observed data in mice.

  12. Inactivation of Tsc2 in Mesoderm-Derived Cells Causes Polycystic Kidney Lesions and Impairs Lung Alveolarization.

    Science.gov (United States)

    Ren, Siying; Luo, Yongfeng; Chen, Hui; Warburton, David; Lam, Hilaire C; Wang, Larry L; Chen, Ping; Henske, Elizabeth P; Shi, Wei

    2016-12-01

    The tuberous sclerosis complex (TSC) proteins are critical negative regulators of the mammalian/mechanistic target of rapamycin complex 1 pathway. Germline mutations of TSC1 or TSC2 cause TSC, affecting multiple organs, including the kidney and lung, and causing substantial morbidity and mortality. The mechanisms of organ-specific disease in TSC remain incompletely understood, and the impact of TSC inactivation on mesenchymal lineage cells has not been specifically studied. We deleted Tsc2 specifically in mesoderm-derived mesenchymal cells of multiple organs in mice using the Dermo1-Cre driver. The Dermo1-Cre-driven Tsc2 conditional knockout mice had body growth retardation and died approximately 3 weeks after birth. Significant phenotypes were observed in the postnatal kidney and lung. Inactivation of Tsc2 in kidney mesenchyme caused polycystic lesions starting from the second week of age, with increased cell proliferation, tubular epithelial hyperplasia, and epithelial-mesenchymal transition. In contrast, Tsc2 deletion in lung mesenchyme led to decreased cell proliferation, reduced postnatal alveolarization, and decreased differentiation with reduced numbers of alveolar myofibroblast and type II alveolar epithelial cells. Two major findings thus result from this model: inactivation of Tsc2 in mesoderm-derived cells causes increased cell proliferation in the kidneys but reduced proliferation in the lungs, and inactivation of Tsc2 in mesoderm-derived cells causes epithelial-lined renal cysts. Therefore, Tsc2-mTOR signaling in mesenchyme is essential for the maintenance of renal structure and for lung alveolarization. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  13. Non-canonical Wnt5a/Ror2 signaling regulates kidney morphogenesis by controlling intermediate mesoderm extension.

    Science.gov (United States)

    Yun, Kangsun; Ajima, Rieko; Sharma, Nirmala; Costantini, Frank; Mackem, Susan; Lewandoski, Mark; Yamaguchi, Terry P; Perantoni, Alan O

    2014-12-20

    Congenital anomalies of the kidney and urinary tract (CAKUT) affect about 1 in 500 births and are a major cause of morbidity in infants. Duplex collecting systems rank among the most common abnormalities of CAKUT, but the molecular basis for this defect is poorly understood. In mice, conditional deletion of Wnt5a in mesoderm results in bilateral duplex kidney and ureter formation. The ureteric buds (UBs) in mutants emerge as doublets from the intermediate mesoderm (IM)-derived nephric duct (ND) without anterior expansion of the glial cell line-derived neurotrophic factor (Gdnf) expression domain in the surrounding mesenchyme. Wnt5a is normally expressed in a graded manner at the posterior end of the IM, but its expression is down-regulated prior to UB outgrowth at E10.5. Furthermore, ablation of Wnt5a in the mesoderm with an inducible Cre at E7.5 results in duplex UBs, whereas ablation at E8.5 yields normal UB outgrowth, demonstrating that Wnt5a functions in IM development well before the formation of the metanephros. In mutants, the posterior ND is duplicated and surrounding Pax2-positive mesenchymal cells persist in the nephric cord, suggesting that disruption of normal ND patterning prompts the formation of duplex ureters and kidneys. Ror2 homozygous mutants, which infrequently yield duplex collecting systems, show a dramatic increase in incidence with the additional deletion of one copy of Wnt5a, implicating this receptor in non-canonical Wnt5a signaling during IM development. This work provides the first evidence of a role of Wnt5a/Ror2 signaling in IM extension and offers new insights into the etiology of CAKUT and possible involvement of Wnt5a/Ror2 mutations. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  14. Gata4 expression in lateral mesoderm is downstream of BMP4 and isactivated directly by Forkhead and GATA transcription factors through adistal enhancer element

    Energy Technology Data Exchange (ETDEWEB)

    Rojas, Anabel; De Val, Sarah; Heidt, Analeah B.; Xu, Shan-Mei; Bristow, James; Black, Brian L.

    2005-05-20

    The GATA family of zinc-finger transcription factors plays key roles in the specification and differentiation of multiple cell types during development. GATA4 is an early regulator of gene expression during the development of endoderm and mesoderm, and genetic studies in mice have demonstrated that GATA4 is required for embryonic development.Despite the importance of GATA4 in tissue specification and differentiation, the mechanisms by which Gata4 expression is activated and the transcription factor pathways upstream of GATA4 remain largely undefined. To identify transcriptional regulators of Gata4 in the mouse,we screened conserved noncoding sequences from the mouse Gata4 gene for enhancer activity in transgenic embryos. Here, we define the regulation of a distal enhancer element from Gata4 that is sufficient to direct expression throughout the lateral mesoderm, beginning at 7.5 days of mouse embryonic development. The activity of this enhancer is initially broad but eventually becomes restricted to the mesenchyme surrounding the liver. We demonstrate that the function of this enhancer in transgenic embryos is dependent upon highly conserved Forkhead and GATA transcription factor binding sites, which are bound by FOXF1 and GATA4,respectively. Furthermore, the activity of the Gata4 lateral mesoderm enhancer is attenuated by the BMP antagonist Noggin, and the enhancer is not activated in Bmp4-null embryos. Thus, these studies establish that Gata4 is a direct transcriptional target of Forkhead and GATA transcription factors in the lateral mesoderm, and demonstrate that Gata4lateral mesoderm enhancer activation requires BMP4, supporting a model in which GATA4 serves as a downstream effector of BMP signaling in the lateral mesoderm.

  15. Simultaneous occurrence of a supra- and an infratentorial glioma in a patient with Ollier's disease : more evidence for non-mesodermal tumor predisposition in multiple enchondromatosis

    NARCIS (Netherlands)

    Heeg, M; Klein, JP; Krikke, AP

    1998-01-01

    A case is presented in which two neuro-ectodermal tumors, an infra- and a supratentorial glioma, developed in a young man with multiple enchondromatosis of Ollier's disease. This is the third such case of multifocal low-grade glioma in Ollier's disease, suggesting a predisposition for non-mesodermal

  16. Light and electron microscopic studies of the intestinal epithelium in Notoplana humilis (Platyhelminthes, Polycladida): the contribution of mesodermal/gastrodermal neoblasts to intestinal regeneration.

    Science.gov (United States)

    Okano, Daisuke; Ishida, Sachiko; Ishiguro, Sei-ichi; Kobayashi, Kazuya

    2015-12-01

    Some free-living flatworms in the phylum Platyhelminthes possess strong regenerative capability that depends on putative pluripotent stem cells known as neoblasts. These neoblasts are defined based on several criteria, including their proliferative capacity and the presence of cellular components known as chromatoid bodies. Polyclads, which are marine flatworms, have the potential to be a good model system for stem cell research, yet little information is available regarding neoblasts and regeneration. In this study, transmission electron microscopy and immunostaining analyses, using antibodies against phospho-histone H3 and BrdU, were used to identify two populations of neoblasts in the polyclad Notoplana humilis: mesodermal neoblasts (located in the mesenchymal space) and gastrodermal neoblasts (located within the intestine, where granular club cells and phagocytic cells are also located). Light and electron microscopic analyses also suggested that phagocytic cells and mesodermal/gastrodermal neoblasts, but not granular club cells, migrated into blastemas and remodeled the intestine during regeneration. Therefore, we suggest that, in polyclads, intestinal regeneration is accomplished by mechanisms underlying both morphallaxis (remodeling of pre-existing tissues) and epimorphosis (de novo tissue formation derived from mesodermal/gastrodermal neoblasts). Based on the assumption that gastrodermal neoblasts, which are derived from mesodermal neoblasts, are intestinal stem cells, we propose a model to study intestinal regeneration.

  17. Effect of angiotensin II on proliferation and differentiation of mouse induced pluripotent stem cells into mesodermal progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Ishizuka, Toshiaki, E-mail: tishizu@ndmc.ac.jp [Department of Pharmacology, National Defense Medical College, Tokorozawa, Saitama 359-8513 (Japan); Goshima, Hazuki; Ozawa, Ayako; Watanabe, Yasuhiro [Department of Pharmacology, National Defense Medical College, Tokorozawa, Saitama 359-8513 (Japan)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer Treatment with angiotensin II enhanced LIF-induced DNA synthesis of mouse iPS cells. Black-Right-Pointing-Pointer Angiotensin II may enhance the DNA synthesis via induction of superoxide. Black-Right-Pointing-Pointer Treatment with angiotensin II significantly increased JAK/STAT3 phosphorylation. Black-Right-Pointing-Pointer Angiotensin II enhanced differentiation into mesodermal progenitor cells. Black-Right-Pointing-Pointer Angiotensin II may enhance the differentiation via activation of p38 MAPK. -- Abstract: Previous studies suggest that angiotensin receptor stimulation may enhance not only proliferation but also differentiation of undifferentiated stem/progenitor cells. Therefore, in the present study, we determined the involvement of the angiotensin receptor in the proliferation and differentiation of mouse induced pluripotent stem (iPS) cells. Stimulation with angiotensin II (Ang II) significantly increased DNA synthesis in mouse iPS cells cultured in a medium with leukemia inhibitory factor (LIF). Pretreatment of the cells with either candesartan (a selective Ang II type 1 receptor [AT{sub 1}R] antagonist) or Tempol (a cell-permeable superoxide scavenger) significantly inhibited Ang II-induced DNA synthesis. Treatment with Ang II significantly increased JAK/STAT3 phosphorylation. Pretreatment with candesartan significantly inhibited Ang II- induced JAK/STAT3 phosphorylation. In contrast, induction of mouse iPS cell differentiation into Flk-1-positive mesodermal progenitor cells was performed in type IV collagen (Col IV)- coated dishes in a differentiation medium without LIF. When Col IV-exposed iPS cells were treated with Ang II for 5 days, the expression of Flk-1 was significantly increased compared with that in the cells treated with the vehicle alone. Pretreatment of the cells with both candesartan and SB203580 (a p38 MAPK inhibitor) significantly inhibited the Ang II- induced increase in Flk-1 expression

  18. Morphological comparison of the craniofacial phenotypes of mouse models expressing the Apert FGFR2 S252W mutation in neural crest- or mesoderm-derived tissues.

    Science.gov (United States)

    Heuzé, Yann; Singh, Nandini; Basilico, Claudio; Jabs, Ethylin Wang; Holmes, Greg; Richtsmeier, Joan T

    2014-06-01

    Bones of the craniofacial skeleton are derived from two distinct cell lineages, cranial neural crest and mesoderm, and articulate at sutures and synchondroses which represent major bone growth sites. Premature fusion of cranial suture(s) is associated with craniofacial dysmorphogenesis caused in part by alteration in the growth potential at sutures and can occur as an isolated birth defect or as part of a syndrome, such as Apert syndrome. Conditional expression of the Apert FGFR2 S252W mutation in cells derived from mesoderm was previously shown to be necessary and sufficient to cause coronal craniosynostosis. Here we used micro computed tomography images of mice expressing the Apert mutation constitutively in either mesoderm- or neural crest-derived cells to quantify craniofacial shape variation and suture fusion patterns, and to identify shape changes in craniofacial bones derived from the lineage not expressing the mutation, referred to here as secondary shape changes. Our results show that at postnatal day 0: (i) conditional expression of the FGFR2 S252W mutation in neural crest-derived tissues causes a more severe craniofacial phenotype than when expressed in mesoderm-derived tissues; and (ii) both mesoderm- and neural crest-specific mouse models display secondary shape changes. We also show that premature suture fusion is not necessarily dependent on the expression of the FGFR2 S252W mutation in the sutural mesenchyme. More specifically, it appears that suture fusion patterns in both mouse models are suture-specific resulting from a complex combination of the influence of primary abnormalities of biogenesis or signaling within the sutures, and timing. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Fli+ etsrp+ hemato-vascular progenitor cells proliferate at the lateral plate mesoderm during vasculogenesis in zebrafish.

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    Chang Zoon Chun

    2011-02-01

    Full Text Available Vasculogenesis, the de novo formation of blood vessels from precursor cells is critical for a developing embryo. However, the signals and events that dictate the formation of primary axial vessels remain poorly understood.In this study, we use ets-related protein-1 (etsrp, which is essential for vascular development, to analyze the early stages of vasculogenesis in zebrafish. We found etsrp(+ cells of the head, trunk and tail follow distinct developmental sequences. Using a combination of genetic, molecular and chemical approaches, we demonstrate that fli(+etsrp(+ hemato-vascular progenitors (FEVPs are proliferating at the lateral plate mesoderm (LPM. The Shh-VEGF-Notch-Hey2 signaling pathway controls the proliferation process, and experimental modulation of single components of this pathway alters etsrp(+ cell numbers at the LPM.This study for the first time defines factors controlling proliferation, and cell numbers of pre-migratory FEVPs in zebrafish.

  20. Loss of abdominal muscle in Pitx2 mutants associated with altered axial specification of lateral plate mesoderm.

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    Diana Eng

    Full Text Available Sequence specific transcription factors (SSTFs combinatorially define cell types during development by forming recursively linked network kernels. Pitx2 expression begins during gastrulation, together with Hox genes, and becomes localized to the abdominal lateral plate mesoderm (LPM before the onset of myogenesis in somites. The somatopleure of Pitx2 null embryos begins to grow abnormally outward before muscle regulatory factors (MRFs or Pitx2 begin expression in the dermomyotome/myotome. Abdominal somites become deformed and stunted as they elongate into the mutant body wall, but maintain normal MRF expression domains. Subsequent loss of abdominal muscles is therefore not due to defects in specification, determination, or commitment of the myogenic lineage. Microarray analysis was used to identify SSTF families whose expression levels change in E10.5 interlimb body wall biopsies. All Hox9-11 paralogs had lower RNA levels in mutants, whereas genes expressed selectively in the hypaxial dermomyotome/myotome and sclerotome had higher RNA levels in mutants. In situ hybridization analyses indicate that Hox gene expression was reduced in parts of the LPM and intermediate mesoderm of mutants. Chromatin occupancy studies conducted on E10.5 interlimb body wall biopsies showed that Pitx2 protein occupied chromatin sites containing conserved bicoid core motifs in the vicinity of Hox 9-11 and MRF genes. Taken together, the data indicate that Pitx2 protein in LPM cells acts, presumably in combination with other SSTFs, to repress gene expression, that are normally expressed in physically adjoining cell types. Pitx2 thereby prevents cells in the interlimb LPM from adopting the stable network kernels that define sclerotomal, dermomyotomal, or myotomal mesenchymal cell types. This mechanism may be viewed either as lineage restriction or specification.

  1. Loss of abdominal muscle in Pitx2 mutants associated with altered axial specification of lateral plate mesoderm.

    Science.gov (United States)

    Eng, Diana; Ma, Hsiao-Yen; Xu, Jun; Shih, Hung-Ping; Gross, Michael K; Kioussi, Chrissa; Kiouss, Chrissa

    2012-01-01

    Sequence specific transcription factors (SSTFs) combinatorially define cell types during development by forming recursively linked network kernels. Pitx2 expression begins during gastrulation, together with Hox genes, and becomes localized to the abdominal lateral plate mesoderm (LPM) before the onset of myogenesis in somites. The somatopleure of Pitx2 null embryos begins to grow abnormally outward before muscle regulatory factors (MRFs) or Pitx2 begin expression in the dermomyotome/myotome. Abdominal somites become deformed and stunted as they elongate into the mutant body wall, but maintain normal MRF expression domains. Subsequent loss of abdominal muscles is therefore not due to defects in specification, determination, or commitment of the myogenic lineage. Microarray analysis was used to identify SSTF families whose expression levels change in E10.5 interlimb body wall biopsies. All Hox9-11 paralogs had lower RNA levels in mutants, whereas genes expressed selectively in the hypaxial dermomyotome/myotome and sclerotome had higher RNA levels in mutants. In situ hybridization analyses indicate that Hox gene expression was reduced in parts of the LPM and intermediate mesoderm of mutants. Chromatin occupancy studies conducted on E10.5 interlimb body wall biopsies showed that Pitx2 protein occupied chromatin sites containing conserved bicoid core motifs in the vicinity of Hox 9-11 and MRF genes. Taken together, the data indicate that Pitx2 protein in LPM cells acts, presumably in combination with other SSTFs, to repress gene expression, that are normally expressed in physically adjoining cell types. Pitx2 thereby prevents cells in the interlimb LPM from adopting the stable network kernels that define sclerotomal, dermomyotomal, or myotomal mesenchymal cell types. This mechanism may be viewed either as lineage restriction or specification.

  2. A data analysis framework for biomedical big data: Application on mesoderm differentiation of human pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Benjamin Ulfenborg

    Full Text Available The development of high-throughput biomolecular technologies has resulted in generation of vast omics data at an unprecedented rate. This is transforming biomedical research into a big data discipline, where the main challenges relate to the analysis and interpretation of data into new biological knowledge. The aim of this study was to develop a framework for biomedical big data analytics, and apply it for analyzing transcriptomics time series data from early differentiation of human pluripotent stem cells towards the mesoderm and cardiac lineages. To this end, transcriptome profiling by microarray was performed on differentiating human pluripotent stem cells sampled at eleven consecutive days. The gene expression data was analyzed using the five-stage analysis framework proposed in this study, including data preparation, exploratory data analysis, confirmatory analysis, biological knowledge discovery, and visualization of the results. Clustering analysis revealed several distinct expression profiles during differentiation. Genes with an early transient response were strongly related to embryonic- and mesendoderm development, for example CER1 and NODAL. Pluripotency genes, such as NANOG and SOX2, exhibited substantial downregulation shortly after onset of differentiation. Rapid induction of genes related to metal ion response, cardiac tissue development, and muscle contraction were observed around day five and six. Several transcription factors were identified as potential regulators of these processes, e.g. POU1F1, TCF4 and TBP for muscle contraction genes. Pathway analysis revealed temporal activity of several signaling pathways, for example the inhibition of WNT signaling on day 2 and its reactivation on day 4. This study provides a comprehensive characterization of biological events and key regulators of the early differentiation of human pluripotent stem cells towards the mesoderm and cardiac lineages. The proposed analysis framework can be

  3. Rapid and efficient differentiation of human pluripotent stem cells into intermediate mesoderm that forms tubules expressing kidney proximal tubular markers.

    Science.gov (United States)

    Lam, Albert Q; Freedman, Benjamin S; Morizane, Ryuji; Lerou, Paul H; Valerius, M Todd; Bonventre, Joseph V

    2014-06-01

    Human pluripotent stem cells (hPSCs) can generate a diversity of cell types, but few methods have been developed to derive cells of the kidney lineage. Here, we report a highly efficient system for differentiating human embryonic stem cells and induced pluripotent stem cells (referred to collectively as hPSCs) into cells expressing markers of the intermediate mesoderm (IM) that subsequently form tubule-like structures. Treatment of hPSCs with the glycogen synthase kinase-3β inhibitor CHIR99021 induced BRACHYURY(+)MIXL1(+) mesendoderm differentiation with nearly 100% efficiency. In the absence of additional exogenous factors, CHIR99021-induced mesendodermal cells preferentially differentiated into cells expressing markers of lateral plate mesoderm with minimal IM differentiation. However, the sequential treatment of hPSCs with CHIR99021 followed by fibroblast growth factor-2 and retinoic acid generated PAX2(+)LHX1(+) cells with 70%-80% efficiency after 3 days of differentiation. Upon growth factor withdrawal, these PAX2(+)LHX1(+) cells gave rise to apically ciliated tubular structures that coexpressed the proximal tubule markers Lotus tetragonolobus lectin, N-cadherin, and kidney-specific protein and partially integrated into embryonic kidney explant cultures. With the addition of FGF9 and activin, PAX2(+)LHX1(+) cells specifically differentiated into cells expressing SIX2, SALL1, and WT1, markers of cap mesenchyme nephron progenitor cells. Our findings demonstrate the effective role of fibroblast growth factor signaling in inducing IM differentiation in hPSCs and establish the most rapid and efficient system whereby hPSCs can be differentiated into cells with features characteristic of kidney lineage cells. Copyright © 2014 by the American Society of Nephrology.

  4. A data analysis framework for biomedical big data: Application on mesoderm differentiation of human pluripotent stem cells.

    Science.gov (United States)

    Ulfenborg, Benjamin; Karlsson, Alexander; Riveiro, Maria; Améen, Caroline; Åkesson, Karolina; Andersson, Christian X; Sartipy, Peter; Synnergren, Jane

    2017-01-01

    The development of high-throughput biomolecular technologies has resulted in generation of vast omics data at an unprecedented rate. This is transforming biomedical research into a big data discipline, where the main challenges relate to the analysis and interpretation of data into new biological knowledge. The aim of this study was to develop a framework for biomedical big data analytics, and apply it for analyzing transcriptomics time series data from early differentiation of human pluripotent stem cells towards the mesoderm and cardiac lineages. To this end, transcriptome profiling by microarray was performed on differentiating human pluripotent stem cells sampled at eleven consecutive days. The gene expression data was analyzed using the five-stage analysis framework proposed in this study, including data preparation, exploratory data analysis, confirmatory analysis, biological knowledge discovery, and visualization of the results. Clustering analysis revealed several distinct expression profiles during differentiation. Genes with an early transient response were strongly related to embryonic- and mesendoderm development, for example CER1 and NODAL. Pluripotency genes, such as NANOG and SOX2, exhibited substantial downregulation shortly after onset of differentiation. Rapid induction of genes related to metal ion response, cardiac tissue development, and muscle contraction were observed around day five and six. Several transcription factors were identified as potential regulators of these processes, e.g. POU1F1, TCF4 and TBP for muscle contraction genes. Pathway analysis revealed temporal activity of several signaling pathways, for example the inhibition of WNT signaling on day 2 and its reactivation on day 4. This study provides a comprehensive characterization of biological events and key regulators of the early differentiation of human pluripotent stem cells towards the mesoderm and cardiac lineages. The proposed analysis framework can be used to structure

  5. Transient Downregulation of Nanog and Oct4 Induced by DETA/NO Exposure in Mouse Embryonic Stem Cells Leads to Mesodermal/Endodermal Lineage Differentiation

    Directory of Open Access Journals (Sweden)

    Sergio Mora-Castilla

    2014-01-01

    Full Text Available The function of pluripotency genes in differentiation is a matter of investigation. We report here that Nanog and Oct4 are reexpressed in two mouse embryonic stem cell (mESC lines following exposure to the differentiating agent DETA/NO. Both cell lines express a battery of both endoderm and mesoderm markers following induction of differentiation with DETA/NO-based protocols. Confocal analysis of cells undergoing directed differentiation shows that the majority of cells expressing Nanog express also endoderm genes such as Gata4 and FoxA2 (75.4% and 96.2%, resp.. Simultaneously, mRNA of mesodermal markers Flk1 and Mef2c are also regulated by the treatment. Acetylated histone H3 occupancy at the promoter of Nanog is involved in the process of reexpression. Furthermore, Nanog binding to the promoter of Brachyury leads to repression of this gene, thus disrupting mesendoderm transition.

  6. Mesodermal repression of single-minded in Drosophila embryo is mediated by a cluster of Snail-binding sites proximal to the early promoter

    Directory of Open Access Journals (Sweden)

    Kye Won Park1 & Joung-Woo Hong2,*

    2012-10-01

    Full Text Available single-minded (sim is a master regulatory gene that directs differentiationin the central nervous system during Drosophilaembryogenesis. Recent identification of the mesectoderm enhancer(MSE of sim has led to the hypothesis that two Snail(Sna-binding sites in the MSE may repress sim expression inthe presumptive mesoderm. We provide evidence here thatthree Sna-binding sites proximal to the sim promoter, but notthose of the MSE, are responsible for the mesodermal repressionof sim in vivo. Using transgenic embryos injectedwith lacZ transgenes, we showed that sim repression in themesoderm requires the three promoter-proximal Sna-bindingsites. These results suggest that Sna represses the mesectodermalexpression of sim by directly repressing the nearby promoter,and not by quenching adjacent transcriptional activatorsin the MSE. These data also showed how the MSE, lackingthe three proximal Sna-binding sites, reproduced the endogenouspattern of sim expression in transgenic embryos.

  7. Mesodermal expression of Fgfr2S252W is necessary and sufficient to induce craniosynostosis in a mouse model of Apert syndrome

    Science.gov (United States)

    Basilico, Claudio

    2013-01-01

    Coordinated growth of the skull and brain are vital to normal human development. Craniosynostosis, the premature fusion of the calvarial bones of the skull, is a relatively common pediatric disease, occurring in 1 in 2500 births, and requires significant surgical management, especially in syndromic cases. Syndromic craniosynostosis is caused by a variety of genetic lesions, most commonly by activating mutations of FGFRs 1–3, and inactivating mutations of TWIST1. In a mouse model of TWIST1 haploinsufficiency, cell mixing between the neural crest-derived frontal bone and mesoderm-derived parietal bone accompanies coronal suture fusion during embryonic development. However, the relevance of lineage mixing in craniosynostosis induced by activating FGFR mutations is unknown. Here, we demonstrate a novel mechanism of suture fusion in the Apert Fgfr2S252W mouse model. Using Cre/lox recombination we simultaneously induce expression of Fgfr2S252W and β-galactosidase in either the neural crest or mesoderm of the skull. We show that mutation of the mesoderm alone is necessary and sufficient to cause craniosynostosis, while mutation of the neural crest is neither. The lineage border is not disrupted by aberrant cell migration during fusion. Instead, the suture mesenchyme itself remains intact and is induced to undergo osteogenesis. We eliminate postulated roles for dura mater or skull base changes in craniosynostosis. The viability of conditionally mutant mice also allows post-natal assessment of other aspects of Apert syndrome. PMID:22664175

  8. An exclusively mesodermal origin of fin mesenchyme demonstrates that zebrafish trunk neural crest does not generate ectomesenchyme.

    Science.gov (United States)

    Lee, Raymond Teck Ho; Knapik, Ela W; Thiery, Jean Paul; Carney, Thomas J

    2013-07-01

    The neural crest is a multipotent stem cell population that arises from the dorsal aspect of the neural tube and generates both non-ectomesenchymal (melanocytes, peripheral neurons and glia) and ectomesenchymal (skeletogenic, odontogenic, cartilaginous and connective tissue) derivatives. In amniotes, only cranial neural crest generates both classes, with trunk neural crest restricted to non-ectomesenchyme. By contrast, it has been suggested that anamniotes might generate derivatives of both classes at all axial levels, with trunk neural crest generating fin osteoblasts, scale mineral-forming cells and connective tissue cells; however, this has not been fully tested. The cause and evolutionary significance of this cranial/trunk dichotomy, and its absence in anamniotes, are debated. Recent experiments have disputed the contribution of fish trunk neural crest to fin osteoblasts and scale mineral-forming cells. This prompted us to test the contribution of anamniote trunk neural crest to fin connective tissue cells. Using genetics-based lineage tracing in zebrafish, we find that these fin mesenchyme cells derive entirely from the mesoderm and that neural crest makes no contribution. Furthermore, contrary to previous suggestions, larval fin mesenchyme cells do not generate the skeletogenic cells of the adult fin, but persist to form fibroblasts associated with adult fin rays. Our data demonstrate that zebrafish trunk neural crest does not generate ectomesenchymal derivatives and challenge long-held ideas about trunk neural crest fate. These findings have important implications for the ontogeny and evolution of the neural crest.

  9. Atmospheric-pressure plasma-irradiation inhibits mouse embryonic stem cell differentiation to mesoderm and endoderm but promotes ectoderm differentiation

    Science.gov (United States)

    Miura, Taichi; Hamaguchi, Satoshi; Nishihara, Shoko

    2016-04-01

    Recently, various effects of low-temperature atmospheric-pressure plasma irradiation on living cells have been demonstrated, such as tissue sterilization, blood coagulation, angiogenesis, wound healing, and tumor elimination. However, the effect of plasma-irradiation on the differentiation of mouse embryonic stem cells (mESCs) has not yet been clarified. A large number of reactive species are generated by plasma-irradiation in medium, of which hydrogen peroxide (H2O2) is one of the main species generated. Here, we investigated the effect of plasma-irradiation on the differentiation of mESCs using an embryoid body (EB) formation assay with plasma-irradiated medium or H2O2-supplemented non-irradiated medium. Our findings demonstrated that plasma-irradiated medium potently inhibits the differentiation from mESCs to mesoderm and endoderm by inhibiting Wnt signaling as determined by quantitative polymerase chain reaction and immunoblotting analyses. In contrast, both the plasma-irradiated medium and H2O2-supplemented non-irradiated medium enhanced the differentiation to epiblastoid, ectodermal, and neuronal lineages by activation of fibroblast growth factor 4 (FGF4) signaling, suggesting that these effects are caused by the H2O2 generated by plasma-irradiation in medium. However, in each case, the differentiation to glial cells remained unaffected. This study is the first demonstration that plasma-irradiation affects the differentiation of mESCs by the regulation of Wnt and FGF4 signaling pathways.

  10. Regulation of cranial morphogenesis and cell fate at the neural crest-mesoderm boundary by engrailed 1

    Science.gov (United States)

    Deckelbaum, Ron A.; Holmes, Greg; Zhao, Zhicheng; Tong, Chunxiang; Basilico, Claudio; Loomis, Cynthia A.

    2012-01-01

    The characterization of mesenchymal progenitors is central to understanding development, postnatal pathology and evolutionary adaptability. The precise identity of the mesenchymal precursors that generate the coronal suture, an important structural boundary in mammalian skull development, remains unclear. We show in mouse that coronal suture progenitors originate from hedgehog-responsive cephalic paraxial mesoderm (Mes) cells, which migrate rapidly to a supraorbital domain and establish a unidirectional lineage boundary with neural crest (NeuC) mesenchyme. Lineage tracing reveals clonal and stereotypical expansion of supraorbital mesenchymal cells to form the coronal suture between E11.0 and E13.5. We identify engrailed 1 (En1) as a necessary regulator of cell movement and NeuC/Mes lineage boundary positioning during coronal suture formation. In addition, we provide genetic evidence that En1 functions upstream of fibroblast growth factor receptor 2 (Fgfr2) in regulating early calvarial osteogenic differentiation, and postulate that it plays an additional role in precluding premature osteogenic conversion of the sutural mesenchyme. PMID:22395741

  11. An exclusively mesodermal origin of fin mesenchyme demonstrates that zebrafish trunk neural crest does not generate ectomesenchyme

    Science.gov (United States)

    Lee, Raymond Teck Ho; Knapik, Ela W.; Thiery, Jean Paul; Carney, Thomas J.

    2013-01-01

    The neural crest is a multipotent stem cell population that arises from the dorsal aspect of the neural tube and generates both non-ectomesenchymal (melanocytes, peripheral neurons and glia) and ectomesenchymal (skeletogenic, odontogenic, cartilaginous and connective tissue) derivatives. In amniotes, only cranial neural crest generates both classes, with trunk neural crest restricted to non-ectomesenchyme. By contrast, it has been suggested that anamniotes might generate derivatives of both classes at all axial levels, with trunk neural crest generating fin osteoblasts, scale mineral-forming cells and connective tissue cells; however, this has not been fully tested. The cause and evolutionary significance of this cranial/trunk dichotomy, and its absence in anamniotes, are debated. Recent experiments have disputed the contribution of fish trunk neural crest to fin osteoblasts and scale mineral-forming cells. This prompted us to test the contribution of anamniote trunk neural crest to fin connective tissue cells. Using genetics-based lineage tracing in zebrafish, we find that these fin mesenchyme cells derive entirely from the mesoderm and that neural crest makes no contribution. Furthermore, contrary to previous suggestions, larval fin mesenchyme cells do not generate the skeletogenic cells of the adult fin, but persist to form fibroblasts associated with adult fin rays. Our data demonstrate that zebrafish trunk neural crest does not generate ectomesenchymal derivatives and challenge long-held ideas about trunk neural crest fate. These findings have important implications for the ontogeny and evolution of the neural crest. PMID:23739134

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

    Directory of Open Access Journals (Sweden)

    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.

  13. A novel signal induces a segmentation fissure by acting in a ventral-to-dorsal direction in the presomitic mesoderm.

    Science.gov (United States)

    Sato, Yuki; Takahashi, Yoshiko

    2005-06-01

    We describe here a novel inductive action that operates during somitic segmentation in chicken embryos. We previously reported that the posterior border cells located at a next-forming boundary in the anterior end of the presomitic mesoderm (PSM) exhibit an inductive activity that acts on the anterior cells to cause the formation of a somitic fissure (Sato, Y., Yasuda, K., Takahashi, Y., 2002. Morphological boundary forms by a novel inductive event mediated by Lunatic fringe and Notch during somitic segmentation. Development 129, 3633-3644). In this study, we have found a second inductive action along the dorso-ventral (D-V) axis during fissure formation. When relocated into a non-segmenting region of PSM, the ventral-most cells taken from the presumptive boundary are sufficient to induce an ectopic fissure in host cells. The ventrally derived signal acts in a ventral-to-dorsal direction but not ventrally, regardless of where the ventral cells are placed. This directional signaling is governed, at least in part, by the signal-receiving cells of the PSM, which we found to be polarized along the D-V axis, and also by intimate cell-cell interactions. Finally, we have observed that morphological segmentation is able to rearrange the anterior and posterior regionalization of individual somites. These findings suggest that discrete unidirectional signals along both the antero-posterior and the D-V axes act coordinately to achieve the formation of the intersomitic fissure, and also that fissure formation is important for the fine-tuning of A-P regionalization in individual somites.

  14. Ascorbic acid drives the differentiation of mesoderm-derived embryonic stem cells. Involvement of p38 MAPK/CREB and SVCT2 transporter.

    Science.gov (United States)

    Rahman, Fryad; Bordignon, Benoit; Culerrier, Raphael; Peiretti, Franck; Spicuglia, Salvatore; Djabali, Malek; Landrier, Jean François; Fontes, Michel

    2017-05-01

    Here we tested the hypothesis that ascorbic acid (AA) is a signaling molecule acting on stem cells via the differentiation of mesoderm derivatives, including myocytes, osteocytes, and adipocytes. Investigations used a murine embryonic stem cell line CGR8 able to differentiate into different cell types and treated or not with ascorbic acid. Differentiation was tracked mainly through cellular anatomy (including presence of beating cardiomyocytes) and expression of specific markers. The study demonstrated that AA drives mesoderm-derived stem cell differentiation toward myogenesis and osteogenesis and also inhibits adipogenesis. Further experiments found that AA competes with retinoic acid (RA) to drive cell differentiation in a dose-dependent manner: AA inhibited neurogenic differentiation and stimulated myogenesis whereas RA did the reverse. The AA-dependent differentiation of embryonic stem cells was shown to involve a p38 MAPK/CREB pathway, probably stimulated by cAMP via adenylate cyclases. In addition, SVCT2, the intracellular transporter of AA, acted as a receptor. Finally, we showed that activation/repression of specific differentiation markers is associated with epigenetic changes in their associated promoters. We discuss the impact of these findings in terms of obesity and aging. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. The murine Nck SH2/SH3 adaptors are important for the development of mesoderm-derived embryonic structures and for regulating the cellular actin network.

    Science.gov (United States)

    Bladt, Friedhelm; Aippersbach, Elke; Gelkop, Sigal; Strasser, Geraldine A; Nash, Piers; Tafuri, Anna; Gertler, Frank B; Pawson, Tony

    2003-07-01

    Mammalian Nck1 and Nck2 are closely related adaptor proteins that possess three SH3 domains, followed by an SH2 domain, and are implicated in coupling phosphotyrosine signals to polypeptides that regulate the actin cytoskeleton. However, the in vivo functions of Nck1 and Nck2 have not been defined. We have mutated the murine Nck1 and Nck2 genes and incorporated beta-galactosidase reporters into the mutant loci. In mouse embryos, the two Nck genes have broad and overlapping expression patterns. They are functionally redundant in the sense that mice deficient for either Nck1 or Nck2 are viable, whereas inactivation of both Nck1 and Nck2 results in profound defects in mesoderm-derived notochord and embryonic lethality at embryonic day 9.5. Fibroblast cell lines derived from Nck1(-/-) Nck2(-/-) embryos have defects in cell motility and in the organization of the lamellipodial actin network. These data suggest that the Nck SH2/SH3 adaptors have important functions in the development of mesodermal structures during embryogenesis, potentially linked to a role in cell movement and cytoskeletal organization.

  16. PSA-NCAM-Negative Neural Crest Cells Emerging during Neural Induction of Pluripotent Stem Cells Cause Mesodermal Tumors and Unwanted Grafts

    Science.gov (United States)

    Lee, Dongjin R.; Yoo, Jeong-Eun; Lee, Jae Souk; Park, Sanghyun; Lee, Junwon; Park, Chul-Yong; Ji, Eunhyun; Kim, Han-Soo; Hwang, Dong-Youn; Kim, Dae-Sung; Kim, Dong-Wook

    2015-01-01

    Summary Tumorigenic potential of human pluripotent stem cells (hPSCs) is an important issue in clinical applications. Despite many efforts, PSC-derived neural precursor cells (NPCs) have repeatedly induced tumors in animal models even though pluripotent cells were not detected. We found that polysialic acid-neural cell adhesion molecule (PSA-NCAM)− cells among the early NPCs caused tumors, whereas PSA-NCAM+ cells were nontumorigenic. Molecular profiling, global gene analysis, and multilineage differentiation of PSA-NCAM− cells confirm that they are multipotent neural crest stem cells (NCSCs) that could differentiate into both ectodermal and mesodermal lineages. Transplantation of PSA-NCAM− cells in a gradient manner mixed with PSA-NCAM+ cells proportionally increased mesodermal tumor formation and unwanted grafts such as PERIPHERIN+ cells or pigmented cells in the rat brain. Therefore, we suggest that NCSCs are a critical target for tumor prevention in hPSC-derived NPCs, and removal of PSA-NCAM− cells eliminates the tumorigenic potential originating from NCSCs after transplantation. PMID:25937368

  17. PRMT8 Controls the Pluripotency and Mesodermal Fate of Human Embryonic Stem Cells By Enhancing the PI3K/AKT/SOX2 Axis.

    Science.gov (United States)

    Jeong, Ho-Chang; Park, Soon-Jung; Choi, Jong-Jin; Go, Young-Hyun; Hong, Soon-Ki; Kwon, Ok-Seon; Shin, Joong-Gon; Kim, Rae-Kwon; Lee, Mi-Ok; Lee, Su-Jae; Shin, Hyoung Doo; Moon, Sung-Hwan; Cha, Hyuk-Jin

    2017-09-01

    Basic fibroblast growth factor (bFGF) supplementation is critical to maintain the pluripotency of human pluripotent stem cells (hPSCs) through activation of PI3K/AKT, rather than MEK/ERK pathway. Thus, elaborate molecular mechanisms that preserve PI3K/AKT signaling upon bFGF stimulation may exist in hPSCs. Protein arginine methyltransferase 8 (PRMT8) was expressed and then its level gradually decreased during spontaneous differentiation of human embryonic stem cells (hESCs). PRMT8 loss- or gain-of-function studies demonstrated that PRMT8 contributed to longer maintenance of hESC pluripotency, even under bFGF-deprived conditions. Direct interaction of membrane-localized PRMT8 with p85, a regulatory subunit of PI3K, was associated with accumulation of phosphoinositol 3-phosphate and consequently high AKT activity. Furthermore, the SOX2 induction, which was controlled by the PRMT8/PI3K/AKT axis, was linked to mesodermal lineage differentiation. Thus, we propose that PRMT8 in hESCs plays an important role not only in maintaining pluripotency but also in controlling mesodermal differentiation through bFGF signaling toward the PI3K/AKT/SOX2 axis. Stem Cells 2017;35:2037-2049. © 2017 AlphaMed Press.

  18. Primary Bovine Extra-Embryonic Cultured Cells: A New Resource for the Study of In Vivo Peri-Implanting Phenotypes and Mesoderm Formation.

    Directory of Open Access Journals (Sweden)

    Isabelle Hue

    Full Text Available In addition to nourishing the embryo, extra-embryonic tissues (EETs contribute to early embryonic patterning, primitive hematopoiesis, and fetal health. These tissues are of major importance for human medicine, as well as for efforts to improve livestock efficiency, but they remain incompletely understood. In bovines, EETs are accessible easily, in large amounts, and prior to implantation. We took advantage of this system to describe, in vitro and in vivo, the cell types present in bovine EETs at Day 18 of development. Specifically, we characterized the gene expression patterns and phenotypes of bovine extra-embryonic ectoderm (or trophoblast; bTC, endoderm (bXEC, and mesoderm (bXMC cells in culture and compared them to their respective in vivo micro-dissected cells. After a week of culture, certain characteristics (e.g., gene expression of the in vitro cells were altered with respect to the in vivo cells, but we were able to identify "cores" of cell-type-specific (and substrate-independent genes that were shared between in vitro and in vivo samples. In addition, many cellular phenotypes were cell-type-specific with regard to extracellular adhesion. We evaluated the ability of individual bXMCs to migrate and spread on micro-patterns, and observed that they easily adapted to diverse environments, similar to in vivo EE mesoderm cells, which encounter different EE epithelia to form chorion, yolk sac, and allantois. With these tissue interactions, different functions arose that were detected in silico and corroborated in vivo at D21-D25. Moreover, analysis of bXMCs allowed us to identify the EE cell ring surrounding the embryonic disc (ED at D14-15 as mesoderm cells, which had been hypothesized but not shown prior to this study. We envision these data will serve as a major resource for the future in the analysis of peri-implanting phenotypes in response to the maternal metabolism and contribute to subsequent studies of placental/fetal development in

  19. A population of hematopoietic stem cells derives from GATA4-expressing progenitors located in the placenta and lateral mesoderm of mice.

    Science.gov (United States)

    Cañete, Ana; Carmona, Rita; Ariza, Laura; Sánchez, María José; Rojas, Anabel; Muñoz-Chápuli, Ramón

    2017-04-01

    GATA transcription factors are expressed in the mesoderm and endoderm during development. GATA1-3, but not GATA4, are critically involved in hematopoiesis. An enhancer (G2) of the mouse Gata4 gene directs its expression throughout the lateral mesoderm and the allantois, beginning at embryonic day 7.5, becoming restricted to the septum transversum by embryonic day 10.5, and disappearing by midgestation. We have studied the developmental fate of the G2-Gata4 cell lineage using a G2-Gata4 Cre ;R26R EYFP mouse line. We found a substantial number of YFP + hematopoietic cells of lymphoid, myeloid and erythroid lineages in embryos. Fetal CD41 + /cKit + /CD34 + and Lin - /cKit + /CD31 + YFP + hematopoietic progenitors were much more abundant in the placenta than in the aorta-gonad-mesonephros area. They were clonogenic in the MethoCult assay and fully reconstituted hematopoiesis in myeloablated mice. YFP + cells represented about 20% of the hematopoietic system of adult mice. Adult YFP + hematopoietic stem cells constituted a long-term repopulating, transplantable population. Thus, a lineage of adult hematopoietic stem cells is characterized by the expression of GATA4 in their embryonic progenitors and probably by its extraembryonic (placental) origin, although GATA4 appeared not to be required for hematopoietic stem cell differentiation. Both lineages basically showed similar physiological behavior in normal mice, but clinically relevant properties of this particular hematopoietic stem cell population should be checked in physiopathological conditions. Copyright© Ferrata Storti Foundation.

  20. Microarray analysis of PDGFR alpha+ populations in ES cell differentiation culture identifies genes involved in differentiation of mesoderm and mesenchyme including ARID3b that is essential for development of embryonic mesenchymal cells.

    Science.gov (United States)

    Takebe, Atsushi; Era, Takumi; Okada, Mitsuhiro; Martin Jakt, Lars; Kuroda, Yoshikazu; Nishikawa, Shin-Ichi

    2006-05-01

    An inherent difficulty in using DNA microarray technology on the early mouse embryo is its relatively small size. In this study, we investigated whether use of ES cell differentiation culture, which has no theoretical limit in the number of cells that can be generated, can improve this situation. Seven distinct ES-cell-derived populations were analyzed by DNA microarray and examined for genes whose distribution patterns are similar to those of PDGFRalpha, a gene implicated in differentiation of mesoderm/mesenchymal lineages. Using software developed in our laboratory, we formed a group of 30 genes which showed the highest similarity to PDGFRalpha, 18 of these genes were shown to be involved in development of either mesodermal, mesenchymal or neural crest cells. This list also contains several genes whose role in embryogenesis has not yet been fully identified. One such molecule is mARID3b. The mARID3b expression is found in the paraxial mesoderm and cranial mesenchyme. mARID3b-null mouse showed early embryonic lethality, and most phenotypes of this mutant appear to develop from a failure to generate a sufficient number of cranial mesenchymal cells. These results demonstrate the potential use of ES cell differentiation culture in identifying novel genes playing an indispensable role in embryogenesis.

  1. Tissue Reactivity of the 14F7 Mab Raised against N-Glycolyl GM3 Ganglioside in Tumors of Neuroectodermal, Mesodermal, and Epithelial Origin

    Science.gov (United States)

    Blanco, Rancés; Quintana, Yisel; Blanco, Damián; Cedeño, Mercedes; Rengifo, Charles E.; Frómeta, Milagros; Ríos, Martha; Rengifo, Enrique; Carr, Adriana

    2013-01-01

    The expression of N-glycolylneuraminic acid forming the structure of gangliosides and/or other glycoconjugates (Hanganutziu-Deicher antigen) in human has been considered as a tumor-associated antigen. Specifically, some reports of 14F7 Mab (a highly specific Mab raised against N-glycolyl GM3 ganglioside) reactivity in human tumors have been recently published. Nevertheless, tumors of epithelial origin have been mostly evaluated. The goal of the present paper was to evaluate the immunohistochemical recognition of 14F7 Mab in different human tumors of neuroectodermal, mesodermal, and epithelial origins using an immunoperoxidase staining method. Samples of fetal, normal, and reactive astrocytosis of the brain were also included in the study. In general, nontumoral tissues, as well as, low-grade brain tumors showed no or a limited immunoreaction with 14F7 Mab. Nevertheless, high-grade astrocytomas (III-IV) and neuroblastomas, as well as, sarcomas and thyroid carcinomas were mostly reactive with 14F7. No reaction was evidenced in medulloblastomas and ependymoblastomas. Our data suggest that the expression of N-glycolyl GM3 ganglioside could be related to the aggressive behavior of malignant cells, without depending on the tumor origin. Our data could also support the possible use of N-glycolyl GM3 as a target for both active and passive immunotherapies of malignancies expressing this molecule. PMID:26317019

  2. Hidden in the crowd: primordial germ cells and somatic stem cells in the mesodermal posterior growth zone of the polychaete Platynereis dumerillii are two distinct cell populations

    Directory of Open Access Journals (Sweden)

    Rebscher Nicole

    2012-04-01

    Full Text Available Abstract Background In the polychaete Platynereis, the primordial germ cells (PGCs emerge from the vasa, piwi, and PL10 expressing mesodermal posterior growth zone (MPGZ at the end of larval development, suggesting a post-embryonic formation from stem cells. Methods In order to verify this hypothesis, embryos and larvae were pulse labeled with the proliferation marker 5-ethynyl-2'-deoxyuridine (EdU at different stages of development. Subsequently, the PGCs were visualized in 7-day-old young worms using antibodies against the Vasa protein. Results Surprisingly, the primordial germ cells of Platynereis incorporate EdU only shortly before gastrulation (6-8 hours post fertilization (hpf, which coincides with the emergence of four small blastomeres from the mesoblast lineage. We conclude that these so-called 'secondary mesoblast cells' constitute the definitive PGCs in Platynereis. In contrast, the cells of the MPGZ incorporate EdU only from the pre-trochophore stage onward (14 hpf. Conclusion While PGCs and the cells of the MPGZ in Platynereis are indistinguishable in morphology and both express the germline markers vasa, nanos, and piwi, a distinct cluster of PGCs is detectable anterior of the MPGZ following EdU pulse-labeling. Indeed the PGCs form independently from the stem cells of the MPGZ prior to gastrulation. Our data suggest an early PGC formation in the polychaete by preformation rather than by epigenesis.

  3. Zic3 is required in the extra-cardiac perinodal region of the lateral plate mesoderm for left-right patterning and heart development.

    Science.gov (United States)

    Jiang, Zhengxin; Zhu, Lirong; Hu, Lingyun; Slesnick, Timothy C; Pautler, Robia G; Justice, Monica J; Belmont, John W

    2013-03-01

    Mutations in ZIC3 cause human X-linked heterotaxy and isolated cardiovascular malformations. A mouse model with targeted deletion of Zic3 demonstrates an early role for Zic3 in gastrulation, CNS, cardiac and left-right axial development. The observation of multiple malformations in Zic3(null) mice and the relatively broad expression pattern of Zic3 suggest its important roles in multiple developmental processes. Here, we report that Zic3 is primarily required in epiblast derivatives to affect left-right patterning and its expression in epiblast is necessary for proper transcriptional control of embryonic cardiac development. However, cardiac malformations in Zic3 deficiency occur not because Zic3 is intrinsically required in the heart but rather because it functions early in the establishment of left-right body axis. In addition, we provide evidence supporting a role for Zic3 specifically in the perinodal region of the posterior lateral plate mesoderm for the establishment of laterality. These data delineate the spatial requirement of Zic3 during left-right patterning in the mammalian embryo, and provide basis for further understanding the molecular mechanisms underlying the complex interaction of Zic3 with signaling pathways involved in the early establishment of laterality.

  4. The C. elegans SoxC protein SEM-2 opposes differentiation factors to promote a proliferative blast cell fate in the postembryonic mesoderm

    Science.gov (United States)

    Tian, Chenxi; Shi, Herong; Colledge, Clark; Stern, Michael; Waterston, Robert; Liu, Jun

    2011-01-01

    The proper development of multicellular organisms requires precise regulation and coordination of cell fate specification, cell proliferation and differentiation. Abnormal regulation and coordination of these processes could lead to disease, including cancer. We have examined the function of the sole C. elegans SoxC protein, SEM-2, in the M lineage, which produces the postembryonic mesoderm. We found that SEM-2/SoxC is both necessary and sufficient to promote a proliferating blast cell fate, the sex myoblast fate, over a differentiated striated bodywall muscle fate. A number of factors control the specific expression of sem-2 in the sex myoblast precursors and their descendants. This includes direct control of sem-2 expression by a Hox-PBC complex. The crucial nature of the HOX/PBC factors in directly enhancing expression of this proliferative factor in the C. elegans M lineage suggests a possible more general link between Hox-PBC factors and SoxC proteins in regulating cell proliferation. PMID:21307099

  5. Does the mesodermal derangement in Chiari Type I malformation extend to the cervical spine? Evidence from an analytical morphometric study on cervical paraspinal muscles.

    Science.gov (United States)

    Thakar, Sumit; Kurudi Siddappa, Avinash; Aryan, Saritha; Mohan, Dilip; Sai Kiran, Narayanam Anantha; Hegde, Alangar S

    2017-10-01

    OBJECTIVE The mesodermal derangement in Chiari Type I malformation (CMI) has been postulated to encompass the cervical spine. The objectives of this study were to assess the cross-sectional areas (CSAs) of cervical paraspinal muscles (PSMs) in patients with CMI without syringomyelia, compare them with those in non-CMI subjects, and evaluate their correlations with various factors. METHODS In this retrospective study, the CSAs of cervical PSMs in 25 patients were calculated on T2-weighted axial MR images and computed as ratios with respect to the corresponding vertebral body areas. These values and the cervical taper ratios were then compared with those of age- and sex-matched non-CMI subjects and analyzed with respect to demographic data and clinicoradiological factors. RESULTS Compared with the non-CMI group, the mean CSA values for the rectus capitis minor and all of the subaxial PSMs were lower in the study group, and those of the deep extensors were significantly lower (p = 0.004). The cervical taper ratio was found to be significantly higher in the study cohort (p = 0.0003). A longer duration of symptoms and a steeper cervical taper ratio were independently associated with lower CSA values for the deep extensors (p = 0.04 and p = 0.03, respectively). The presence of neck pain was associated with a lower CSA value for the deep flexors (p = 0.03). CONCLUSIONS Patients with CMI demonstrate alterations in their cervical paraspinal musculature even in the absence of coexistent syringomyelia. Their deep extensor muscles undergo significant atrophic changes that worsen with the duration of their symptoms. This could be related to a significantly steeper cervical taper ratio that their cervical cords are exposed to. Neck pain in these patients is related to atrophy of their deep flexor muscles. A steeper cervical taper ratio and alterations in the PSMs could be additional indicators for surgery in patients with CMI without syringomyelia.

  6. The C. elegans Spalt-like protein SEM-4 functions through the SoxC transcription factor SEM-2 to promote a proliferative blast cell fate in the postembryonic mesoderm.

    Science.gov (United States)

    Shen, Qinfang; Shi, Herong; Tian, Chenxi; Ghai, Vikas; Liu, Jun

    2017-09-01

    Proper development of a multicellular organism relies on well-coordinated regulation of cell fate specification, cell proliferation and cell differentiation. The C. elegans postembryonic mesoderm provides a useful system for uncovering factors involved in these processes and for further dissecting their regulatory relationships. The single Spalt-like zinc finger containing protein SEM-4/SALL is known to be involved in specifying the proliferative sex myoblast (SM) fate. We have found that SEM-4/SALL is sufficient to promote the SM fate and that it does so in a cell autonomous manner. We further showed that SEM-4/SALL acts through the SoxC transcription factor SEM-2 to promote the SM fate. SEM-2 is known to promote the SM fate by inhibiting the expression of two BWM-specifying transcription factors. In light of recent findings in mammals showing that Sall4, one of the mammalian homologs of SEM-4, contributes to pluripotency regulation by inhibiting differentiation, our work suggests that the function of SEM-4/SALL proteins in regulating pluripotency versus differentiation appears to be evolutionarily conserved. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Malignant mixed mesodermal tumor of the ovary

    NARCIS (Netherlands)

    Elbers, J.R.J.; Wagenaar, S.S.

    Mixed mesenchymal and epithelial tumors are highly malignant neoplasms most commonly found in the uterus. Rarely, histologically identical tumors occur in the ovary. We report a 70-yr-old woman with a malignant mixed Müllerian tumor of the ovary. The tumor contained heterologous foci of immature

  8. Contribution of mesoderm to the developing dental papilla

    Czech Academy of Sciences Publication Activity Database

    Rothová, Michaela; Feng, J.; Sharpe, P. T.; Peterková, Renata; Tucker, A. S.

    2011-01-01

    Roč. 55, č. 1 (2011), s. 59-64 ISSN 0214-6282 R&D Projects: GA ČR GA304/07/0223 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : tooth * dental papilla * Mesp1cre Subject RIV: EA - Cell Biology Impact factor: 2.823, year: 2011

  9. Segmentation of the paraxial mesoderm and vertebrate somitogenesis.

    Science.gov (United States)

    Pourquié, O

    2000-01-01

    Somites are the most obviously segmented features of the vertebrate embryo. Although the way segmentation is achieved in the fly is now well described, little was known about the molecular mechanisms underlying vertebrate somitogenesis. Through the recent identification of genes important for vertebrate somitogenesis and the analysis of their function, several theoretical models accounting for somitogenesis such as the clock and wavefront model, which have been proposed over the past 20 years, are now starting to receive experimental support. A molecular clock linked to somitogenesis has been identified which might act as a periodicity generator in the presomitic cells. This temporal periodicity is then translated into a tightly controlled spatial periodicity which is revealed by the expression of several genes. Analysis of mouse mutants in the Notch-Delta pathway suggest that this signaling mechanism might play an important role at this level. The final step of the cascade is to translate these genetically specified segments into morphological units: the somites. Importantly, these studies have helped in dissociating the segmentation and the somitogenesis processes in vertebrates. In addition, although segmentation was classically thought to have arisen independently in protostomes and deuterostomes, recent evidence suggests that part of the segmentation machinery might actually have been conserved. The conservation of segmentation mechanisms reported in the fly such as the pair-rule pattern, however, remain a subject of controversy.

  10. Insulin redirects differentiation from cardiogenic mesoderm and endoderm to neuroectoderm in differentiating human embryonic stem cells.

    NARCIS (Netherlands)

    Freund, C.M.A.H.; Ward-van Oostwaard, D.; Monshouwer-Kloots, J.; van den Brink, S.; van Rooijen, M.A.; Xu, X.; Zweigerdt, R.; Mummery, C.L.; Passier, R.

    2008-01-01

    Human embryonic stem cells (hESC) can proliferate indefinitely while retaining the capacity to form derivatives of all three germ layers. We have reported previously that hESC differentiate into cardiomyocytes when cocultured with a visceral endoderm-like cell line (END-2). Insulin/insulin-like

  11. Utx Is Required for Proper Induction of Ectoderm and Mesoderm during Differentiation of Embryonic Stem Cells

    DEFF Research Database (Denmark)

    Morales Torres, Cristina; Laugesen, Anne; Helin, Kristian

    2013-01-01

    for the activation of lineage choice genes in response to developmental signals. To further understand the function of Utx in pluripotency and differentiation we generated Utx knockout embryonic stem cells (ESCs). Here we show that Utx is not required for the proliferation of ESCs, however, Utx contributes......Embryonic development requires chromatin remodeling for dynamic regulation of gene expression patterns to ensure silencing of pluripotent transcription factors and activation of developmental regulators. Demethylation of H3K27me3 by the histone demethylases Utx and Jmjd3 is important...

  12. Krüppel-like is required for nonskeletogenic mesoderm specification in the sea urchin embryo.

    Science.gov (United States)

    Yamazaki, Atsuko; Kawabata, Rika; Shiomi, Kosuke; Tsuchimoto, Jun; Kiyomoto, Masato; Amemiya, Shonan; Yamaguchi, Masaaki

    2008-02-15

    The canonical Wnt pathway plays a central role in specifying vegetal cell fate in sea urchin embryos. SpKrl has been cloned as a direct target of nuclear beta-catenin. Using Hemicentrotus pulcherrimus embryos, here we show that HpKrl controls the specification of secondary mesenchyme cells (SMCs) through both cell-autonomous and non-autonomous means. Like SpKrl, HpKrl was activated in both micromere and macromere progenies. To examine the functions of HpKrl in each blastomere, we constructed chimeric embryos composed of blastomeres from control and morpholino-mediated HpKrl-knockdown embryos and analyzed the phenotypes of the chimeras. Micromere-swapping experiments showed that HpKrl is not involved in micromere specification, while micromere-deprivation assays indicated that macromeres require HpKrl for cell-autonomous specification. Transplantation of normal micromeres into a micromere-less host with morpholino revealed that macromeres are able to receive at least some micromere signals regardless of HpKrl function. From these observations, we propose that two distinct pathways of endomesoderm formation exist in macromeres, a Krl-dependent pathway and a Krl-independent pathway. The Krl-independent pathway may correspond to the Delta/Notch signaling pathway via GataE and Gcm. We suggest that Krl may be a downstream component of nuclear beta-catenin required by macromeres for formation of more vegetal tissues, not as a member of the Delta/Notch pathway, but as a parallel effector of the signaling (Krl-dependent pathway).

  13. Krüppel-like is required for nonskeletogenic mesoderm specification in the sea urchin embryo

    OpenAIRE

    Yamazaki, Atsuko; Kawabata, Rika; Shiomi, Kosuke; Tsuchimoto, Jun; Kiyomoto, Masato; Amemiya, Shonan; Yamaguchi, Masaaki

    2008-01-01

    The canonical Wnt pathway plays a central role in specifying vegetal cell fate in sea urchin embryos. SpKrl has been cloned as a direct target of nuclear β-catenin. Using Hemicentrotus pulcherrimus embryos, here we show that HpKrl controls the specification of secondary mesenchyme cells (SMCs) through both cell-autonomous and non-autonomous means. Like SpKrl, HpKrl was activated in both micromere and macromere progenies. To examine the functions of HpKrl in each blastomere, we constructed chi...

  14. Octopod, a homeotic mutation of the moth Manduca sexta, affects development of both mesodermal and ectodermal structures.

    Science.gov (United States)

    Miles, C I; Booker, R

    1993-01-01

    Several aspects of leg development in the moth Manduca sexta were examined using the homeotic mutation Octopod (Octo). This mutation causes a transformation of the ventral epidermis of the first abdominal segment (A1) to that of the third thoracic segment (T3), resulting in the presence of thoracic-like legs on A1. The degree of transformation of A1 is variable, ranging from bumps on the cuticle to fully segmented thoracic-like legs. In the normal thoracic legs, clusters of undifferentiated cells known as differentiation centers are located around the coxal-trochanteral, femoral-tibial, and tibial-tarsal joints. The adult thoracic legs develop from the differentiation centers at metamorphosis. The homeotic legs of the Octopod larvae also have differentiation centers at comparable positions in the homeotic leg. As a result, the number of leg segments in a mutant adult is correlated with the number of segments and differentiation centers that animal had in its larval homeotic leg. Our data suggest that the differentiation center located at the coxal-trochanteral joint forms the adult coxa and trochanter, the center at the larval femoral-tibial joint the adult femur and tibia, and the differentiation center at the larval tibial-tarsal joint the adult tarsus. Homeotic larval legs which include at least a femur have supernumerary muscles, while adult homeotic legs rarely show discrete muscle. The homeotic larval muscles appear to have thoracic identities, based on their attachment points and the timing of their degeneration at the larval-pupal transition. They are innervated by a motoneuron that is normally present in A1 where it innervates the ventral lateral external muscle (VLE). In mutant animals, the same motoneuron innervates all of the homeotic muscles and the VLE. We consider possible mechanisms underlying the development of homeotic muscles and their innervation. At the larval-pupal transition, the VLE in mutant animals degenerates at its normal time, which is 3 days after the degeneration of the homeotic muscles. Thus, despite their common innervation, the two muscle types degenerate according to their own schedules, indicating that the developmental fates of the muscles are not dictated by their innervating neuron but are intrinsic to the muscles themselves.

  15. An exclusively mesodermal origin of fin mesenchyme demonstrates that zebrafish trunk neural crest does not generate ectomesenchyme

    OpenAIRE

    Lee, Raymond Teck Ho; Knapik, Ela W.; Thiery, Jean Paul; Carney, Thomas J.

    2013-01-01

    The neural crest is a multipotent stem cell population that arises from the dorsal aspect of the neural tube and generates both non-ectomesenchymal (melanocytes, peripheral neurons and glia) and ectomesenchymal (skeletogenic, odontogenic, cartilaginous and connective tissue) derivatives. In amniotes, only cranial neural crest generates both classes, with trunk neural crest restricted to non-ectomesenchyme. By contrast, it has been suggested that anamniotes might generate derivatives of both c...

  16. GETDB: 113106 [GETDB

    Lifescience Database Archive (English)

    Full Text Available enetics. - Link to clone table - 1 807 Link to cluster table 807 1 Request - mesoderm from gustrulation. good... - Embryonic Expression mesoderm from gustrulation. good for mesodermal driver. L

  17. Analysis of the Hand1 cell lineage reveals novel contributions to cardiovascular, neural crest, extra-embryonic, and lateral mesoderm derivatives.

    Science.gov (United States)

    Barnes, Ralston M; Firulli, Beth A; Conway, Simon J; Vincentz, Joshua W; Firulli, Anthony B

    2010-11-01

    The basic Helix-Loop-Helix (bHLH) transcription factors Hand1 and Hand2 play critical roles in the development of multiple organ systems during embryogenesis. The dynamic expression patterns of these two factors within developing tissues obfuscate their respective unique and redundant organogenic functions. To define cell lineages potentially dependent upon Hand gene expression, we generated a mutant allele in which the coding region of Hand1 is replaced by Cre recombinase. Subsequent Cre-mediated activation of β-galactosidase or eYFP reporter alleles enabled lineage trace analyses that clearly define the fate of Hand1-expressing cells. Hand1-driven Cre marks specific lineages within the extra embryonic tissues, placenta, sympathetic nervous system, limbs, jaw, and several cell types within the cardiovascular system. Comparisons between Hand1 expression and Hand1-lineage greatly refine our understanding of its dynamic spatial-temporal expression domains and raise the possibility of novel Hand1 functions in structures not thought to be Hand1-dependent. © 2010 Wiley-Liss, Inc.

  18. A comprehensive gene expression analysis at sequential stages of in vitro cardiac differentiation from isolated MESP1-expressing-mesoderm progenitors

    NARCIS (Netherlands)

    den Hartogh, Sabine C.; Wolstencroft, Katherine; Mummery, Christine L.; Passier, Robert

    2016-01-01

    In vitro cardiac differentiation of human pluripotent stem cells (hPSCs) closely recapitulates in vivo embryonic heart development, and therefore, provides an excellent model to study human cardiac development. We recently generated the dual cardiac fluorescent reporter MESP1mCherry/w NKX2-5eGFP/w

  19. Defective neuronal migration and inhibition of bipolar to multipolar transition of migrating neural cells by Mesoderm-Specific Transcript, Mest, in the developing mouse neocortex.

    Science.gov (United States)

    Ji, Liting; Bishayee, Kausik; Sadra, Ali; Choi, Seunghyuk; Choi, Wooyul; Moon, Sungho; Jho, Eek-Hoon; Huh, Sung-Oh

    2017-07-04

    Brain developmental disorders such as lissencephaly can result from faulty neuronal migration and differentiation during the formation of the mammalian neocortex. The cerebral cortex is a modular structure, where developmentally, newborn neurons are generated as a neuro-epithelial sheet and subsequently differentiate, migrate and organize into their final positions in the cerebral cortical plate via a process involving both tangential and radial migration. The specific role of Mest, an imprinted gene, in neuronal migration has not been previously studied. In this work, we reduced expression of Mest with in utero electroporation of neuronal progenitors in the developing embryonic mouse neocortex. Reduction of Mest levels by shRNA significantly reduced the number of neurons migrating to the cortical plate. Also, Mest-knockdown disrupted the transition of bipolar neurons into multipolar neurons migrating out of the sub-ventricular zone region. The migrating neurons also adopted a more tangential migration pattern upon knockdown of the Mest message, losing their potential to attach to radial glia cells, required for radial migration. The differentiation and migration properties of neurons via Wnt-Akt signaling were affected by Mest changes. In addition, miR-335, encoded in a Mest gene intron, was identified as being responsible for blocking the default tangential migration of the neurons. Our results suggest that Mest and its intron product, miR-335, play important roles in neuronal migration with Mest regulating the morphological transition of primary neurons required in the formation of the mammalian neocortex. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Stem Cell Information: Glossary

    Science.gov (United States)

    ... Long-term self-renewal Meiosis Mesenchymal stem cells Mesoderm Microenvironment Mitosis Multipotent Neural stem cell Neurons Oligodendrocyte ... layers. The three layers are the ectoderm , the mesoderm , and the endoderm . Hematopoietic stem cell - A stem ...

  1. BMP regulates vegetal pole induction centres in early xenopus development.

    Science.gov (United States)

    Nachaliel, N; Re'Em-Kalma, Y; Eshed, O; Elias, S; Frank, D

    1998-10-01

    Bone morphogenetic protein (BMP) plays an important role in mesoderm patterning in Xenopus. The ectopic expression of BMP-4 protein hyperventralizes embryos, whereas embryos expressing a BMP-2/4 dominant-negative receptor (DNR) are hyperdorsalized. Mesoderm is initially induced in the marginal zone by cells in the underlying vegetal pole. While much is known about BMP's expression and role in patterning the marginal zone, little is known about its early role in regulating vegetal mesoderm induction centre formation. The role of BMP in regulating formation of vegetal mesoderm inducing centres during early Xenopus development was examined. Ectopic BMP-4 expression in vegetal pole cells inhibited dorsal mesoderm induction but increased ventral mesoderm induction when recombined with animal cap ectoderm in Nieuwkoop explants. 32-cell embryos injected with BMP-4 RNA in the most vegetal blastomere tier were not hyperdorsalized by LiCl treatment. The ectopic expression of Smad or Mix.1 proteins in the vegetal pole also inhibited dorsal mesoderm induction in explants and embryos. Expression of the BMP 2/4 DNR in the vegetal pole increased dorsal mesoderm induction and inhibited ventral mesoderm induction in explants and embryos. These results support a role for BMP signalling in regulating ventral vegetal and dorsal vegetal mesoderm induction centre formation during early Xenopus development.

  2. GETDB: 112053 [GETDB

    Lifescience Database Archive (English)

    Full Text Available tute of Genetics. FM7c Link to clone table - 1 340 Link to cluster table 340 1 Request - viseral mesoderm, good...cluster table 340 Num of clusters 1 Stock Request Request - Embryonic Expression viseral mesoderm, good driv

  3. GETDB: 112114 [GETDB

    Lifescience Database Archive (English)

    Full Text Available e National Institute of Genetics. CyUW14 Link to clone table - 1 1246 Link to cluster table 1246 1 Request - v. mesoderm, good...46 Link to Cluster Table Link to cluster table 1246 Num of clusters 1 Stock Request Request - Embryonic Expression v. mesoderm, good

  4. Proteus syndrome: The magnetic resonance and radiological features

    Energy Technology Data Exchange (ETDEWEB)

    Cremin, B.J.; Viljoen, D.L.; Beighton, P.; Wynchank, S.

    1987-10-01

    The Proteus syndrome is a recently delineated group of skeletal and mesodermal malformations. Its characteristics include hemihypertrophy and fatty/lymphangiomatous masses. This description outlines the imaging sequences available to the radiologist. It is mainly concerned with the use of magnetic resonance imaging. This shows the extent of the mesodermal malformation with particular reference to the extent of intra abdominal infiltration.

  5. Mesenchymal stem cells: biological characteristics and potential clinical applications

    DEFF Research Database (Denmark)

    Kassem, Moustapha

    2004-01-01

    Mesenchymal stem cells (MSC) are clonogenic, non-hematpoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages, for example, osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages, for example, neuronal...

  6. Confinement and clearance of OCT4 in the porcine embryo at stereomicroscopically defined stages around gastrulation

    DEFF Research Database (Denmark)

    Vejlsted, Morten; Offenberg, Hanne Kjær; Thorup, Flemming

    2006-01-01

    maintaining expression of OCT4 at the end of gastrulation. In the ectodermal and mesodermal cell lineages, OCT4 became undetectable at the neural groove and somite stage, respectively. As in the mouse, PGCs showed onset of c-kit expression when located in extraembryonal compartments. They appeared to follow...... the endoderm during extraembryonal allocation and the mesoderm on return to the genital ridge....

  7. Mesenchymal stem cells: cell biology and potential use in therapy

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Kristiansen, Malthe; Abdallah, Basem M

    2004-01-01

    Mesenchymal stem cells are clonogenic, non-haematopoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages e.g. osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages e.g. neuronal-like cells. Several methods...

  8. A conserved gene regulatory network subcircuit drives different developmental fates in the vegetal pole of highly divergent echinoderm embryos.

    Science.gov (United States)

    McCauley, Brenna S; Weideman, Erin P; Hinman, Veronica F

    2010-04-15

    Comparisons of orthologous developmental gene regulatory networks (GRNs) from different organisms explain how transcriptional regulation can, or cannot, change over time to cause morphological evolution and stasis. Here, we examine a subset of the GRN connections in the central vegetal pole mesoderm of the late sea star blastula and compare them to the GRN for the same embryonic territory of sea urchins. In modern sea urchins, this territory gives rise to skeletogenic mesoderm; in sea stars, it develops into other mesodermal derivatives. Orthologs of many transcription factors that function in the sea urchin skeletogenic mesoderm are co-expressed in the sea star vegetal pole, although this territory does not form a larval skeleton. Systematic perturbation of erg, hex, tbr, and tgif gene function was used to construct a snapshot of the sea star mesoderm GRN. A comparison of this network to the sea urchin skeletogenic mesoderm GRN revealed a conserved, recursively wired subcircuit operating in both organisms. We propose that, while these territories have evolved different functions in sea urchins and sea stars, this subcircuit is part of an ancestral GRN governing echinoderm vegetal pole mesoderm development. The positive regulatory feedback between these transcription factors may explain the conservation of this subcircuit. Copyright (c) 2009. Published by Elsevier Inc.

  9. Induction of primordial germ cell-like cells from mouse embryonic stem cells by ERK signal inhibition.

    Science.gov (United States)

    Kimura, Tohru; Kaga, Yoshiaki; Ohta, Hiroshi; Odamoto, Mika; Sekita, Yoichi; Li, Kunpeng; Yamano, Noriko; Fujikawa, Keita; Isotani, Ayako; Sasaki, Norihiko; Toyoda, Masashi; Hayashi, Katsuhiko; Okabe, Masaru; Shinohara, Takashi; Saitou, Mitinori; Nakano, Toru

    2014-10-01

    Primordial germ cells (PGCs) are embryonic germ cell precursors. Specification of PGCs occurs under the influence of mesodermal induction signaling during in vivo gastrulation. Although bone morphogenetic proteins and Wnt signaling play pivotal roles in both mesodermal and PGC specification, the signal regulating PGC specification remains unknown. Coculture of mouse embryonic stem cells (ESCs) with OP9 feeder cells induces mesodermal differentiation in vitro. Using this mesodermal differentiation system, we demonstrated that PGC-like cells were efficiently induced from mouse ESCs by extracellular signal-regulated kinase (ERK) signaling inhibition. Inhibition of ERK signaling by a MAPK/ERK kinase (MEK) inhibitor upregulated germ cell marker genes but downregulated mesodermal genes. In addition, the PGC-like cells showed downregulation of DNA methylation and formed pluripotent stem cell colonies upon treatment with retinoic acid. These results show that inhibition of ERK signaling suppresses mesodermal differentiation but activates germline differentiation program in this mesodermal differentiation system. Our findings provide a new insight into the signaling networks regulating PGC specification. © 2014 AlphaMed Press.

  10. Origins and Properties of Dental, Thymic, and Bone Marrow Mesenchymal Cells and Their Stem Cells

    Science.gov (United States)

    Komada, Yukiya; Yamane, Toshiyuki; Kadota, Daiji; Isono, Kana; Takakura, Nobuyuki; Hayashi, Shin-Ichi; Yamazaki, Hidetoshi

    2012-01-01

    Mesenchymal cells arise from the neural crest (NC) or mesoderm. However, it is difficult to distinguish NC-derived cells from mesoderm-derived cells. Using double-transgenic mouse systems encoding P0-Cre, Wnt1-Cre, Mesp1-Cre, and Rosa26EYFP, which enabled us to trace NC-derived or mesoderm-derived cells as YFP-expressing cells, we demonstrated for the first time that both NC-derived (P0- or Wnt1-labeled) and mesoderm-derived (Mesp1-labeled) cells contribute to the development of dental, thymic, and bone marrow (BM) mesenchyme from the fetal stage to the adult stage. Irrespective of the tissues involved, NC-derived and mesoderm-derived cells contributed mainly to perivascular cells and endothelial cells, respectively. Dental and thymic mesenchyme were composed of either NC-derived or mesoderm-derived cells, whereas half of the BM mesenchyme was composed of cells that were not derived from the NC or mesoderm. However, a colony-forming unit-fibroblast (CFU-F) assay indicated that CFU-Fs in the dental pulp, thymus, and BM were composed of NC-derived and mesoderm-derived cells. Secondary CFU-F assays were used to estimate the self-renewal potential, which showed that CFU-Fs in the teeth, thymus, and BM were entirely NC-derived cells, entirely mesoderm-derived cells, and mostly NC-derived cells, respectively. Colony formation was inhibited drastically by the addition of anti-platelet–derived growth factor receptor-β antibody, regardless of the tissue and its origin. Furthermore, dental mesenchyme expressed genes encoding critical hematopoietic factors, such as interleukin-7, stem cell factor, and cysteine-X-cysteine (CXC) chemokine ligand 12, which supports the differentiation of B lymphocytes and osteoclasts. Therefore, the mesenchymal stem cells found in these tissues had different origins, but similar properties in each organ. PMID:23185234

  11. Experiment list: SRX150603 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available mesoderm|Description=lymphoblastoid, International HapMap Project, Han Chinese in Beijing, China, treatment:...GM18526 || cell organism=human || cell description=lymphoblastoid, International HapMap Project, Han Chinese

  12. Assessment of the Developmental Toxicity of Epidermal Growth ...

    African Journals Online (AJOL)

    H and glial fibrillary acidic protein (GFAP), mesodermal-specific ... example, NGF may be of critical importance for ovarian follicles [2]. Insulin-like growth ..... those of whole embryo culture, ES cell micro mass cultivation, testicular cells, ovarian ...

  13. Experiment list: SRX150466 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available mesoderm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Cauca...ription=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah -

  14. Experiment list: SRX150367 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available mesoderm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, tr... || cell=GM12891 || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  15. Cloacal Exstrophy : An Epidemiologic Study From the International Clearinghouse for Birth Defects Surveillance and Research

    NARCIS (Netherlands)

    Feldkamp, Marcia L.; Botto, Lorenzo D.; Amar, Emmanuelle; Bakker, Marian K.; Bermejo-Sanchez, Eva; Bianca, Sebastiano; Canfield, Mark A.; Castilla, Eduardo E.; Clementi, Maurizio; Csaky-Szunyogh, Melinda; Leoncini, Emanuele; Li, Zhu; Lowry, R. Brian; Mastroiacovo, Pierpaolo; Merlob, Paul; Morgan, Margery; Mutchinick, Osvaldo M.; Rissmann, Anke; Ritvanen, Annukka; Siffel, Csaba; Carey, John C.

    2011-01-01

    Cloacal exstrophy presents as a complex abdominal wall defect thought to result from a mesodermal abnormality. Anatomically, its main components are Omphalocele, bladder Exstrophy and Imperforate anus. Other associated malformations include renal malformations and Spine defects (OEIS complex).

  16. Mesenchymal cells reactivate Snail1 expression to drive three-dimensional invasion programs

    DEFF Research Database (Denmark)

    Rowe, R.G.; Li, X.Y.; Hu, Y.

    2009-01-01

    Epithelial-mesenchymal transition (EMT) is required for mesodermal differentiation during development. The zinc-finger transcription factor, Snail1, can trigger EMT and is sufficient to transcriptionally reprogram epithelial cells toward a mesenchymal phenotype during neoplasia and fibrosis. Whet...

  17. The ctenophore genome and the evolutionary origins of neural systems

    NARCIS (Netherlands)

    Moroz, Leonid L.; Kocot, Kevin M.; Citarella, Mathew R.; Dosung, Sohn; Norekian, Tigran P.; Povolotskaya, Inna S.; Grigorenko, Anastasia P.; Dailey, Christopher; Berezikov, Eugene; Buckley, Katherine M.; Ptitsyn, Andrey; Reshetov, Denis; Mukherjee, Krishanu; Moroz, Tatiana P.; Bobkova, Yelena; Yu, Fahong; Kapitonov, Vladimir V.; Jurka, Jerzy; Bobkov, Yuri V.; Swore, Joshua J.; Girardo, David O.; Fodor, Alexander; Gusev, Fedor; Sanford, Rachel; Bruders, Rebecca; Kittler, Ellen; Mills, Claudia E.; Rast, Jonathan P.; Derelle, Romain; Solovyev, Victor V.; Kondrashov, Fyodor A.; Swalla, Billie J.; Sweedler, Jonathan V.; Rogaev, Evgeny I.; Halanych, Kenneth M.; Kohn, Andrea B.

    2014-01-01

    The origins of neural systems remain unresolved. In contrast to other basal metazoans, ctenophores (comb jellies) have both complex nervous and mesoderm-derived muscular systems. These holoplanktonic predators also have sophisticated ciliated locomotion, behaviour and distinct development. Here we

  18. Experiment list: SRX100400 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available mesoderm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Cauca...ll description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion,

  19. Experiment list: SRX150719 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available mesoderm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, tr... || cell=GM12892 || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  20. Experiment list: SRX150405 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available mesoderm|Description=lymphoblastoid, International HapMap Project, Yoruba in Ibadan, Nigera, treatment: Epst...193 || cell organism=human || cell description=lymphoblastoid, International HapMap Project, Yoruba in Ibada

  1. Experiment list: SRX100444 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available mesoderm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, tr...datatype description=Chromatin IP Sequencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  2. Experiment list: SRX100530 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available mesoderm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Cauca... cell description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasio

  3. Identification and fate mapping of the pancreatic mesenchyme.

    Science.gov (United States)

    Angelo, Jesse R; Tremblay, Kimberly D

    2018-03-01

    The murine pancreas buds from the ventral embryonic endoderm at approximately 8.75 dpc and a second pancreas bud emerges from the dorsal endoderm by 9.0 dpc. Although it is clear that secreted signals from adjacent mesoderm-derived sources are required for both the appropriate emergence and further refinement of the pancreatic endoderm, neither the exact signals nor the requisite tissue sources have been defined in mammalian systems. Herein we use DiI fate mapping of cultured murine embryos to identify the embryonic sources of both the early inductive and later condensed pancreatic mesenchyme. Despite being capable of supporting pancreas induction from dorsal endoderm in co-culture experiments, we find that in the context of the developing embryo, the dorsal aortae as well as the paraxial, intermediate, and lateral mesoderm derivatives only transiently associate with the dorsal pancreas bud, producing descendants that are decidedly anterior to the pancreas bud. Unlike these other mesoderm derivatives, the axial (notochord) descendants maintain association with the dorsal pre-pancreatic endoderm and early pancreas bud. This fate mapping data points to the notochord as the likely inductive source in vivo while also revealing dynamic morphogenetic movements displayed by individual mesodermal subtypes. Because none of the mesoderm examined above produced the pancreatic mesenchyme that condenses around the induced bud to support exocrine and endocrine differentiation, we also sought to identify the mesodermal origins of this mesenchyme. We identify a portion of the coelomic mesoderm that contributes to the condensed pancreatic mesenchyme. In conclusion, we identify a portion of the notochord as a likely source of the signals required to induce and maintain the early dorsal pancreas bud, demonstrate that the coelomic mesothelium contributes to the dorsal and ventral pancreatic mesenchyme, and provide insight into the dynamic morphological rearrangements of mesoderm

  4. The problem of the origin of primordial germ cells (PGCs) in vertebrates: historical review and a possible solution.

    Science.gov (United States)

    Pilato, Giovanni; D'Urso, Vera; Viglianisi, Fabio; Sammartano, Francesca; Sabella, Giorgio; Lisi, Oscar

    2013-01-01

    A concise review of the articles about the origin of primordial germ cells (PGCs) in vertebrates is provided. Differences among various taxa concerning the origin of PGCs, not easily understandable on the base of traditional knowledge, are pointed out. All those differences can be explained taking into consideration the recent “theory of the endoderm as secondary layer”. That theory allows us to understand that those differences are only apparent, being related to modifications of stages of the consequent embryogeny, overall, to a different amount of yolk in the egg. Eggs very rich in yolk became meroblastic, and the portion of primordial ectomesenchyme destined to give rise to a part of the mesoderm and the PGCs separates early from the part destined to give rise to the rest of the mesoderm and to the digestive endoderm in order to form the vitelline hypoblast lamina. To this lamina, in contrast to the traditional interpretation, a mesodermal, not endodermal, origin must be attributed. With the misunderstanding regarding the origin of this lamina clarified, all the differences about the origin of PGCs disappears. Furthermore, in taxa where PGCs were considered to be of endodermal origin, they too have a mesodermal origin. Considering that a mesodermal origin of PGCs has been demonstrated in all sponges and cnidarians, as well, a unique, mesodermal origin of germinal cells in all pluricellular animals results.

  5. A biomechanical analysis of ventral furrow formation in the Drosophila melanogaster embryo.

    Directory of Open Access Journals (Sweden)

    Vito Conte

    Full Text Available The article provides a biomechanical analysis of ventral furrow formation in the Drosophila melanogaster embryo. Ventral furrow formation is the first large-scale morphogenetic movement in the fly embryo. It involves deformation of a uniform cellular monolayer formed following cellularisation, and has therefore long been used as a simple system in which to explore the role of mechanics in force generation. Here we use a quantitative framework to carry out a systematic perturbation analysis to determine the role of each of the active forces observed. The analysis confirms that ventral furrow invagination arises from a combination of apical constriction and apical-basal shortening forces in the mesoderm, together with a combination of ectodermal forces. We show that the mesodermal forces are crucial for invagination: the loss of apical constriction leads to a loss of the furrow, while the mesodermal radial shortening forces are the primary cause of the internalisation of the future mesoderm as the furrow rises. Ectodermal forces play a minor but significant role in furrow formation: without ectodermal forces the furrow is slower to form, does not close properly and has an aberrant morphology. Nevertheless, despite changes in the active mesodermal and ectodermal forces lead to changes in the timing and extent of furrow, invagination is eventually achieved in most cases, implying that the system is robust to perturbation and therefore over-determined.

  6. Prune belly syndrome associated with cloacal anomaly, patent urachal remnant, and omphalocele in a female infant.

    Science.gov (United States)

    Giuliani, Stefano; Vendryes, Christopher; Malhotra, Ajay; Shaul, Donald B; Anselmo, Dean M

    2010-11-01

    Prune belly syndrome (PBS), megacystis-microcolon-intestinal hypoperistalsis (MMIH), and omphalocele-exstrophy of the bladder-imperforate anus-spine abnormalities complex (OEIS) are rare congenital malformations of the newborn that lead to incomplete formation of the gastrointestinal and genitourinary tract systems. To date, incomplete mesodermal development is identified as the cause for all these complex genetic syndromes even if the etiology is still unknown. We present an original case sharing characteristics common to PBS, MMIH, and OEIS complex, without a clear inclination toward any particular one. This case hints toward a common pathway in the creation of the 3 syndromes. We hypothesize that they are a spectrum of malformations based on the time frame when the mesoderm fails to create a normal interaction between infraumbilical mesoderm, urorectal septum, lumbosacral somites in the formation of the abdominal wall and the genitourinary and lower gastrointestinal tracts. Published by Elsevier Inc.

  7. Mesenchymal Stem Cells: Application for Immunomodulation and Tissue Repair

    DEFF Research Database (Denmark)

    Horwood, Nicole J.; Dazzi, Francesco; Zaher, Walid

    2012-01-01

    Mesenchymal stem cells (MSC) are stem cell populations present among the bone marrow stroma and a number of other tissues that are capable of multi-lineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. MSC provide supportive stroma for growth and diffe......Mesenchymal stem cells (MSC) are stem cell populations present among the bone marrow stroma and a number of other tissues that are capable of multi-lineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. MSC provide supportive stroma for growth...

  8. Culture Systems for Regenerative Kidney Therapy

    Science.gov (United States)

    2014-09-01

    which is normally expressed in proximal and distal convoluted tubules and loops of Henle in humans, but is decreased or absent in adult mouse kidneys ...Differentiation of Human Pluripotent Stem Cells into Intermediate Mesoderm That Forms Tubules Expressing Kidney Proximal Tubular Markers. Journal of the...AWARD NUMBER: W81XWH-12-1-0468 TITLE: Culture Systems for Regenerative Kidney Therapy

  9. GETDB: 113235 [GETDB

    Lifescience Database Archive (English)

    Full Text Available f Genetics. - Link to clone table - 1 673 Link to cluster table 673 1 Request - good for driver. mesoderm in...ter id 673 Link to Cluster Table Link to cluster table 673 Num of clusters 1 Stock Request Request - Embryonic Expression good

  10. Melorheostosis | Kingori | East African Orthopaedic Journal

    African Journals Online (AJOL)

    This case study is a report on the rare mesodermal disorder typically characterized by abnormalities of the skeleton and soft tissues. ... but now it has been established that melorheostosis is due to a loss-of-function mutation in LEMD 3 gene (also called MAN 1), which encodes an inner nuclear membrane protein (2). This is ...

  11. PICTORIAL INTERLUDE Gorlin syndrome – an incidental ...

    African Journals Online (AJOL)

    Introduction. Gorlin-Goltz syndrome (also known as nevoid basal cell carcinoma syndrome) was first reported in 1894, but described by Gorlin and Goltz in 1960 as a distinct entity consisting of ectodermal and mesodermal abnormalities.1 It is an hereditary autosomal dominant disease with a prevalence estimated in various ...

  12. The Sweetness of Embryonic Elongation and Differentiation.

    Science.gov (United States)

    Naganathan, Sundar R; Oates, Andrew C

    2017-02-27

    Metabolic pathways play a vital yet poorly understood role in embryogenesis. In this issue of Developmental Cell, Bulusu et al. (2017) and Oginuma et al. (2017) provide insights into the intricate relationship between metabolism and morphogenesis, showing that glycolysis facilitates body elongation and balances neural and mesodermal differentiation. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. The development of the action potential mechanism of amphibian neurons isolated in culture.

    Science.gov (United States)

    Spitzer, N C; Lamborghini, J E

    1976-05-01

    Nerve and muscle cells differentiated morphologically, in cultures of dissociated cells prepared from amphibian neural plate and underlying mesoderm (Xenopus laevis, Nieuwkoop and Faber stage 15). Cultures were grown in a defined medium containing sterile Steinberg's salt solution and 0.1% bovine serum albumin, and maintained for periods up to 5 days.

  14. A systematic analysis of Tinman function reveals Eya and JAK-STAT signaling as essential regulators of muscle development

    DEFF Research Database (Denmark)

    Liu, Ya-Hsin; Jakobsen, Janus S; Valentin, Guillaume

    2009-01-01

    Nk-2 proteins are essential developmental regulators from flies to humans. In Drosophila, the family member tinman is the major regulator of cell fate within the dorsal mesoderm, including heart, visceral, and dorsal somatic muscle. To decipher Tinman's direct regulatory role, we performed a time...

  15. Fibroepithelial polyps causing ureteropelvic junction obstruction in children--a case report and review article.

    Science.gov (United States)

    Cassar Delia, E; Joseph, V T; Sherwood, W

    2007-04-01

    Fibroepithelial polyps are extremely rare benign mesodermal tumours in children that can cause ureteropelvic junction (UPJ) obstruction. We report on a 10-year-old boy presenting with UPJ obstruction due to a fibroepithelial polyp, and review 28 similar published paediatric cases.

  16. Clipboard

    Indian Academy of Sciences (India)

    Madhsudhan

    somites bud off at regular time-intervals from the presomitic mesoderm (PSM) that flanks the notochord and proceed to give rise to vertebrae, ribs, muscle and dorsal dermis (Dequéant and Pourquié 2008). The numbers of segments in mammals, birds and fish are not very different, all falling well under 100, within a factor of ...

  17. Passwell syndrome

    Directory of Open Access Journals (Sweden)

    Muhammed K

    2003-03-01

    Full Text Available There is an expanding list of syndromes that combine ichthyosis with neuroectodermal and mesodermal defects. We report a syndrome of congenital ichthyosis with atrophy, mental retardation, dwarfism, aminoaciduria, primary amenorrhoea and underdeveloped secondary sexual characters in a 38-year-old woman of non consanguinous parentage.

  18. Fusion from myoblasts to myotubes is dependent on the rolling stone gene (rost) of Drosophila.

    Science.gov (United States)

    Paululat, A; Burchard, S; Renkawitz-Pohl, R

    1995-08-01

    The development and differentiation of the body wall musculature in Drosophila are accompanied by changes in gene expression and cellular architecture. We isolated a Drosophila gene, termed rolling stone (rost), which, when mutated, specifically blocks the fusion of mononucleated cells to myotubes in the body wall musculature. beta 3 tubulin, which is an early marker for the onset of mesoderm differentiation, is still expressed in these cells. Gastrulation and mesoderm formation, as well as the development of the epidermis and of the central and peripheral nervous systems, appear quite normal in homozygous rolling stone embryos. Embryonic development stops shortly before hatching in a P-element-induced mutant, as well as in 16 EMS-induced alleles. In mutant embryos, other mesodermal derivatives such as the visceral mesoderm and the dorsal vessel, develop fairly normally and defects are restricted to the body wall musculature. Myoblasts remain as single mononucleated cells, which express muscle myosin, showing that the developmental program of gene expression proceeds. These myoblasts occur at positions corresponding to the locations of dorsal, ventral and pleural muscles, showing that the gene rolling stone is involved in cell fusion, a process that is independent of cell migration in these mutants. This genetic analysis has set the stage for a molecular analysis to clarify where the rolling stone action is manifested in the fusion process and thus gives insight into the complex regulating network controlling the differentiation of the body wall musculature.

  19. Integrative analysis of polychaete ontogeny: cell proliferation patterns and myogenesis in trochophore larvae of Sabellaria alveolata

    DEFF Research Database (Denmark)

    Brinkmann, Nora; Wanninger, Andreas

    2010-01-01

    of this crucial mesoderm-derived organ system, particularly in indirect developing representatives of the Lophotrochozoa. Here, we document the temporal and spatial patterns of muscle formation and cell proliferation in the polychaete Sabellaria alveolata during planktotrophic larval development in order...

  20. Immunohistochemical Localization of Fibrinogen C Domain Containing 1 on Epithelial and Mucosal Surfaces in Human Tissues

    DEFF Research Database (Denmark)

    von Huth, Sebastian; Moeller, Jesper B; Schlosser, Anders

    2018-01-01

    high expression of FIBCD1 and also mesodermal-derived cells in the genitourinary system and ectodermal-derived epidermis and sebaceous glands cells expressed FIBCD1. In some columnar epithelial cells, for example, in the salivary gland and gall bladder, the FIBCD1 expression was clearly polarized...

  1. Genetics Home Reference: hypohidrotic ectodermal dysplasia

    Science.gov (United States)

    ... Affected individuals tend to have sparse scalp and body hair ( hypotrichosis ). The hair is often light-colored, brittle, ... layers form the basis for many of the body's organs and tissues. Ectoderm-mesoderm interactions are essential ... hair, nails, teeth, and sweat glands. Mutations in the ...

  2. GETDB: 112464 [GETDB

    Lifescience Database Archive (English)

    Full Text Available ed from the National Institute of Genetics. FM7c - 2 - - 0 - 2 patterns? (SG) pns sunset (ch), mesoderm cns ...r. 1 Comments NP line. Received from the National Institute of Genetics. Balancer FM7c Link to Clone Table -

  3. Cloning, characterization and promoter analysis of common carp ...

    Indian Academy of Sciences (India)

    Abstract. Some members of hairy/Enhancer-of-split-related gene (HES) family have important effects on axial mesoderm segmentation and the ... transgenic embryos. Our results show that the upstream sequence of 500 bp can direct highly ..... like gene, acts downstream of notch signalling to control somite development.

  4. Cell lineage and cell cycling analyses of the 4d micromere using live imaging in the marine annelidPlatynereis dumerilii.

    Science.gov (United States)

    Özpolat, B Duygu; Handberg-Thorsager, Mette; Vervoort, Michel; Balavoine, Guillaume

    2017-12-12

    Cell lineage, cell cycle, and cell fate are tightly associated in developmental processes, but in vivo studies at single-cell resolution showing the intricacies of these associations are rare due to technical limitations. In this study on the marine annelid Platynereis dumerilii, we investigated the lineage of the 4d micromere, using high-resolution long-term live imaging complemented with a live-cell cycle reporter. 4d is the origin of mesodermal lineages and the germline in many spiralians. We traced lineages at single-cell resolution within 4d and demonstrate that embryonic segmental mesoderm forms via teloblastic divisions, as in clitellate annelids. We also identified the precise cellular origins of the larval mesodermal posterior growth zone. We found that differentially-fated progeny of 4d (germline, segmental mesoderm, growth zone) display significantly different cell cycling. This work has evolutionary implications, sets up the foundation for functional studies in annelid stem cells, and presents newly established techniques for live imaging marine embryos.

  5. Gorlin syndrome – an incidental radiographic detection | Shetty | SA ...

    African Journals Online (AJOL)

    Gorlin-Goltz syndrome (also known as nevoid basal cell carcinoma syndrome) was first reported in 1894, but described by Gorlin and Goltz in 1960 as a distinct entity consisting of ectodermal and mesodermal abnormalities.1 It is an hereditary autosomal dominant disease with a prevalence estimated in various studies to ...

  6. Osteopathia striata: A characteristic X-ray finding in focal dermal hypoplasia (Goltz-Gorlin syndrome)

    International Nuclear Information System (INIS)

    Barthels, W.; Boepple, D.; Petzel, H.

    1982-01-01

    Two cases of the very rare Goltz-Gorlin syndrome are presented. The relationship of osteopathia striata and focal dermal hypoplasia is discussed, and it is concluded that the osteopathia striata represents the characteristic picture of this ectopic mesodermal abnormality. (orig.)

  7. Assessing the bipotency of in vitro-derived neuromesodermal progenitors [v1; ref status: indexed, http://f1000r.es/58z

    Directory of Open Access Journals (Sweden)

    Anestis Tsakiridis

    2015-04-01

    Full Text Available Retrospective clonal analysis in the mouse has demonstrated that the posterior spinal cord neurectoderm and paraxial mesoderm share a common bipotent progenitor. These neuromesodermal progenitors (NMPs are the source of new axial structures during embryonic rostrocaudal axis elongation and are marked by the simultaneous co-expression of the transcription factors T(Brachyury (T(Bra and Sox2. NMP-like cells have recently been derived from pluripotent stem cells in vitro following combined stimulation of Wnt and fibroblast growth factor (FGF signaling. Under these conditions the majority of cultures consist of T(Bra/Sox2 co-expressing cells after 48-72 hours of differentiation. Although the capacity of these cells to generate posterior neural and paraxial mesoderm derivatives has been demonstrated at the population level, it is unknown whether a single in vitro-derived NMP can give rise to both neural and mesodermal cells. Here we demonstrate that T(Bra positive cells obtained from mouse epiblast stem cells (EpiSCs after culture in NMP-inducing conditions can generate both neural and mesodermal clones. This finding suggests that, similar to their embryonic counterparts, in vitro-derived NMPs are truly bipotent and can thus be exploited as a model for studying the molecular basis of developmental cell fate decisions.

  8. The use of mesenchymal (skeletal) stem cells for treatment of degenerative diseases: current status and future perspectives

    DEFF Research Database (Denmark)

    Abdallah, Basem; Kassem, Moustapha

    2009-01-01

    and possibly but not proven to non-mesodermal cell types. Recently, there has been an increased interest in understanding the biology of MSC due to their potential use in cell-based therapy for multiple degenerative diseases. Here, we will provide an update on the current status of these novel therapeutic...

  9. Expression of Id2 in the Second Heart Field and Cardiac Defects in Id2 Knock-Out Mice

    NARCIS (Netherlands)

    Jongbloed, M. R. M.; Vicente-Steijn, R.; Douglas, Y. L.; Wisse, L. J.; Mori, K.; Yokota, Y.; Bartelings, M. M.; Schalij, M. J.; Mahtab, E. A.; Poelmann, R. E.; Gittenberger-De Groot, A. C.

    2011-01-01

    The inhibitor of differentiation Id2 is expressed in mesoderm of the second heart field, which contributes myocardial and mesenchymal cells to the primary heart tube. The role of Id2 in cardiac development is insufficiently known. Heart development was studied in sequential developmental stages in

  10. Hemihypertrophy and the Chiari I malformation.

    Science.gov (United States)

    Tubbs, R Shane; Smyth, Matthew D; Wellons, John C; Oakes, W Jerry

    2003-05-01

    We report two children with hemihypertrophy and Chiari I malformation (CIM) and review the extant medical literature regarding CIM and overgrowth disorders. We propose that these two entities do not represent a spurious association but rather share a common dysembryology of mesoderm. Copyright 2003 S. Karger AG, Basel

  11. Cloning, characterization and promoter analysis of common carp

    Indian Academy of Sciences (India)

    Some members of hairy/Enhancer-of-split-related gene (HES) family have important effects on axial mesoderm segmentation and the establishment and maintenance of the somite fringe. In fishes, the her6 gene, a member of the HES family, is the homologue of hes1 in mammals and chicken. In this study, the her6 gene ...

  12. Experiment list: SRX193586 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available yoblasts || cell karyotype=normal || cell lineage=mesoderm || cell sex=U || labexpid=DS14426 || labversion=Hotspot-v5.2,lmax-v1.0,Win...dowDensity-bin20-win+/-75 http://dbarchive.biosciencedbc

  13. Effect of tissue-harvesting site on yield of stem cells derived from adipose tissue: implications for cell-based therapies

    NARCIS (Netherlands)

    Jurgens, W.J.F.M.; Oedayrajsingh-Varma, M.J.; Helder, M.N.; Zandieh Doulabi, B.; Schouten, T.E.; Kuik, D.J.; Ritt, M.J.P.F.; van Milligen-Kummer, F.J.

    2008-01-01

    The stromal vascular fraction (SVF) of adipose tissue contains an abundant population of multipotent adipose-tissue-derived stem cells (ASCs) that possess the capacity to differentiate into cells of the mesodermal lineage in vitro. For cell-based therapies, an advantageous approach would be to

  14. Mature cystic teratomas: Relationship between histopathological ...

    African Journals Online (AJOL)

    2014-08-09

    Aug 9, 2014 ... [4-6] The detection rate of tumor markers is low, although high levels of CA-19.9 are common in MCT cases.[7] MCTs are composed of endodermal, mesodermal and ectodermal derivatives.[8] Some clinical situations can be associated with the composition of MCT, such as a stromal carcinoid ovarian tumor ...

  15. The Palm-Heart Diameter: A Prospective Simple Screening Tool for Identifying Heart Enlargement

    Directory of Open Access Journals (Sweden)

    Adegbenro Omotuyi John Fakoya

    2017-11-01

    CONCLUSION: This study establishes the correlation between the palm and heart diameters. Since the heart tissue and the upper limb share a similar embryonic origin, being the mesoderm, this study prospects the fact that heart enlargement could be preliminarily identified by measuring the size of the hand.

  16. Connexin43 repression following epithelium-to-mesenchyme transition in embryonal carcinoma cells requires Snail1 transcription factor

    NARCIS (Netherlands)

    de Boer, Teun P.; van Veen, Toon A. B.; Bierhuizen, Marti F. A.; Kok, Bart; Rook, Martin B.; Boonen, Kristel J. M.; Vos, Marc A.; Doevendans, Pieter A.; de Bakker, Jacques M. T.; van der Heyden, Marcel A. G.

    2007-01-01

    Embryonic stem (ES) cells and embryonal carcinoma (EC) cells express high amounts of functional connexin43 (Cx43). During mesoderm formation and subsequent cardiac differentiation, Cx43 is initially down-regulated but is up-regulated again as the emerging cardiomyocytes mature. In this study, we

  17. Conditional deletion of WT1 in the septum transversum mesenchyme causes congenital diaphragmatic hernia in mice.

    Science.gov (United States)

    Carmona, Rita; Cañete, Ana; Cano, Elena; Ariza, Laura; Rojas, Anabel; Muñoz-Chápuli, Ramon

    2016-09-19

    Congenital diaphragmatic hernia (CDH) is a severe birth defect. Wt1-null mouse embryos develop CDH but the mechanisms regulated by WT1 are unknown. We have generated a murine model with conditional deletion of WT1 in the lateral plate mesoderm, using the G2 enhancer of the Gata4 gene as a driver. 80% of G2-Gata4(Cre);Wt1(fl/fl) embryos developed typical Bochdalek-type CDH. We show that the posthepatic mesenchymal plate coelomic epithelium gives rise to a mesenchyme that populates the pleuroperitoneal folds isolating the pleural cavities before the migration of the somitic myoblasts. This process fails when Wt1 is deleted from this area. Mutant embryos show Raldh2 downregulation in the lateral mesoderm, but not in the intermediate mesoderm. The mutant phenotype was partially rescued by retinoic acid treatment of the pregnant females. Replacement of intermediate by lateral mesoderm recapitulates the evolutionary origin of the diaphragm in mammals. CDH might thus be viewed as an evolutionary atavism.

  18. Images in medicine

    African Journals Online (AJOL)

    abp

    Caudal regression is a rare syndrome which has a spectrum of congenital malformations ranging from simple anal atresia to absence of sacral, lumbar and possibly lower thoracic vertebrae. It results from a disturbance in the fetal mesoderm in early pregnancy. (< 4th week of gestation). Maternal diabetes, genetic ...

  19. Cycliophora is a new phylum with affinities to Entoprocta and Ectoprocta

    DEFF Research Database (Denmark)

    Funch, P.; Kristensen, R.M.

    1995-01-01

    aspects of inner budding and brooding of larvae are similar to those of Entoprocta and Ectoprocta. The dispersive larva possesses a mesodermal supporting chordoid structure, otherwise absent in protostomian larvae, We believe that ail the above features of this previously undescribed species warrant...

  20. Experiment list: SRX144527 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available neage=mesoderm|Description=parental cell type to lymphoblastoid cell lines 8704444,92.1,92.5,9 GSM922972: NRF2 ChIP vehicle... treated rep3; Homo sapiens; ChIP-Seq source_name=NRF2 ChIP vehicle treated || biomaterial_pr

  1. Experiment list: SRX144525 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available neage=mesoderm|Description=parental cell type to lymphoblastoid cell lines 14487710,85.8,82.8,188 GSM922970: NRF2 ChIP vehicle... treated rep1; Homo sapiens; ChIP-Seq source_name=NRF2 ChIP vehicle treated || biomaterial

  2. Experiment list: SRX144524 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available neage=mesoderm|Description=parental cell type to lymphoblastoid cell lines 4766716,6.2,89.4,0 GSM922969: NRF2 ChIP vehicle... treated pilot; Homo sapiens; ChIP-Seq source_name=NRF2 ChIP vehicle treated || biomaterial_pr

  3. Pathways in pluripotency and differentiation of embryonic cells

    NARCIS (Netherlands)

    du Puy, L.

    2010-01-01

    Pluripotency - the potential to differentiate into derivatives of the three embryonic germ layers endoderm, ectoderm and mesoderm - is the main characteristic of embryonic stem (ES) cells. ES cells are derived from the inner cell mass (ICM) of a pre-implantation blastocyst and can self-renew

  4. Neurofibromatosis type I — some cranial and spinal manifestations

    African Journals Online (AJOL)

    Enrique

    Introduction. Neurofibromatosis is a hereditary congenital disorder consisting of dys- plasias and tumours of tissues arising from the ectodermal and mesodermal layers of the embryo. The most com- monly encountered subtype is neu- rofibromatosis type 1 (NF-1). Shown in this report are several manifesta- tions of NF-1 ...

  5. Magnetic resonance imaging findings in an unusual case of atlanto axial dislocation and vertebral artery-vein fistulas in a patient of neurofibromatosis-1

    International Nuclear Information System (INIS)

    Maheshwari, S.; Kale, H.A.; Desai, S.B.; Kohli, A.

    2002-01-01

    Neurofibromatosis is a dysplasia of mesodermal and neuroectodermal tissues with potential for diffuse systemic involvement. Vertebral arteriovenous fistulas - abnormal communications of the artery and vein- are uncommon in neurofibromatosis. We describe MRI findings of a patient with an unusual association of bilateral vertebral arteriovenous fistulas with an atlantoaxial dislocation in the setting of neurofibromatosis. Copyright (2002) Blackwell Science Pty Ltd

  6. Case report 556: Multiple non-ossifying fibromas of long bones in a patient with neurofibromatosis

    International Nuclear Information System (INIS)

    Gross, M.L.; Dorfman, H.D.; Seimon, P.; Soberman, N.

    1989-01-01

    This case demonstrates histological evidence of multiple non-ossifying fibromas in a patient with neurofibromatosis. While the association between these lesions remains unclear, the presence of multiple NOF in neurofibromatosis represents further evidence of an underlying mesodermal developmental anomaly. (orig./GDG)

  7. The neural crest and neural crest cells

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    scientific work, and Olsson (2000) for a bibliography. 2.2 1960s–1970s ... Sympathetic nervous system. Peripheral nervous system. Thyroid and Parathyroid glands. Ultimobranchial body. Adrenal gland. Craniofacial skeleton. Teeth. Dentine ..... those cells that leave the mesodermal germ layer during formation of the coelom ...

  8. Work type II first branchial cleft cyst: a rare anomaly with a classical ...

    African Journals Online (AJOL)

    such cases. The branchial apparatus starts to appear between the fourth and the fifth weeks of fetal develop- ment. The apparatus consists of five arches consisting of the mesoderm, four clefts that consist of the ectoderm and four pouches that consist of the endoderm. The first branchial pouch forms the Eustachian tube and ...

  9. Identification, molecular characterization, and analysis of the ...

    Indian Academy of Sciences (India)

    2016; Fu and Shi 2017). The SoxF subgroup transcription factors include three members (Sox7, Sox17, and Sox18) (Zhou et al. 2015). These three genes share some essential functions, including regulation of embryonic development, stem cell induction, and early mesoderm induction (Abdelalim et al. 2014; Kinoshita et al.

  10. Commentary

    Indian Academy of Sciences (India)

    Unknown

    A gospel truth of developmental biology has been that cells are fated to stay in the germ layer from which they arise. Endoderm makes endoderm but not mesoderm or ectoderm. Precursor cells give rise to a limited repertoire of progeny or a restricted lineage, depending on the tissue and position from which they arise.

  11. GETDB: 104230 [GETDB

    Lifescience Database Archive (English)

    Full Text Available mesodermal cells Larval GFP ubiquitous Larval X-gal 2 patterns, sg or gut Adult G...mal cells ubiquitous 2 patterns, sg or gut internal lethal - - d1 - - - Show 1042...ational Institute of Genetics. CyO Link to clone table - 1 919 Link to cluster table 919 1 Request - mesoder

  12. Functional evolution of Ets in echinoderms with focus on the evolution of echinoderm larval skeletons.

    Science.gov (United States)

    Koga, Hiroyuki; Matsubara, Mioko; Fujitani, Haruka; Miyamoto, Norio; Komatsu, Miéko; Kiyomoto, Masato; Akasaka, Koji; Wada, Hiroshi

    2010-09-01

    Convergent evolution of echinoderm pluteus larva was examined from the standpoint of functional evolution of a transcription factor Ets1/2. In sea urchins, Ets1/2 plays a central role in the differentiation of larval skeletogenic mesenchyme cells. In addition, Ets1/2 is suggested to be involved in adult skeletogenesis. Conversely, in starfish, although no skeletogenic cells differentiate during larval development, Ets1/2 is also expressed in the larval mesoderm. Here, we confirmed that the starfish Ets1/2 is indispensable for the differentiation of the larval mesoderm. This result led us to assume that, in the common ancestors of echinoderms, Ets1/2 activates the transcription of distinct gene sets, one for the differentiation of the larval mesoderm and the other for the development of the adult skeleton. Thus, the acquisition of the larval skeleton involved target switching of Ets1/2. Specifically, in the sea urchin lineage, Ets1/2 activated a downstream target gene set for skeletogenesis during larval development in addition to a mesoderm target set. We examined whether this heterochronic activation of the skeletogenic target set was achieved by the molecular evolution of the Ets1/2 transcription factor itself. We tested whether starfish Ets1/2 induced skeletogenesis when injected into sea urchin eggs. We found that, in addition to ectopic induction of mesenchyme cells, starfish Ets1/2 can activate some parts of the skeletogenic pathway in these mesenchyme cells. Thus, we suggest that the nature of the transcription factor Ets1/2 did not change, but rather that some unidentified co-factor(s) for Ets1/2 may distinguish between targets for the larval mesoderm and for skeletogenesis. Identification of the co-factor(s) will be key to understanding the molecular evolution underlying the evolution of the pluteus larvae.

  13. Small molecule-directed specification of sclerotome-like chondroprogenitors and induction of a somitic chondrogenesis program from embryonic stem cells.

    Science.gov (United States)

    Zhao, Jiangang; Li, Songhui; Trilok, Suprita; Tanaka, Makoto; Jokubaitis-Jameson, Vanta; Wang, Bei; Niwa, Hitoshi; Nakayama, Naoki

    2014-10-01

    Pluripotent embryonic stem cells (ESCs) generate rostral paraxial mesoderm-like progeny in 5-6 days of differentiation induced by Wnt3a and Noggin (Nog). We report that canonical Wnt signaling introduced either by forced expression of activated β-catenin, or the small-molecule inhibitor of Gsk3, CHIR99021, satisfied the need for Wnt3a signaling, and that the small-molecule inhibitor of BMP type I receptors, LDN193189, was able to replace Nog. Mesodermal progeny generated using such small molecules were chondrogenic in vitro, and expressed trunk paraxial mesoderm markers such as Tcf15 and Meox1, and somite markers such as Uncx, but failed to express sclerotome markers such as Pax1. Induction of the osteochondrogenically committed sclerotome from somite requires sonic hedgehog and Nog. Consistently, Pax1 and Bapx1 expression was induced when the isolated paraxial mesodermal progeny were treated with SAG1 (a hedgehog receptor agonist) and LDN193189, then Sox9 expression was induced, leading to cartilaginous nodules and particles in the presence of BMP, indicative of chondrogenesis via sclerotome specification. By contrast, treatment with TGFβ also supported chondrogenesis and stimulated Sox9 expression, but failed to induce the expression of Pax1 and Bapx1. On ectopic transplantation to immunocompromised mice, the cartilage particles developed under either condition became similarly mineralized and formed pieces of bone with marrow. Thus, the use of small molecules led to the effective generation from ESCs of paraxial mesodermal progeny, and to their further differentiation in vitro through sclerotome specification into growth plate-like chondrocytes, a mechanism resembling in vivo somitic chondrogenesis that is not recapitulated with TGFβ. © 2014. Published by The Company of Biologists Ltd.

  14. Specification of germ layer identity in the chick gastrula

    Directory of Open Access Journals (Sweden)

    Cai Qin

    2007-07-01

    Full Text Available Abstract Background Chick definitive endoderm is an important source of signals that pattern the early embryo forming a central structure around which the body plan is constructed. Although the origin of definitive endoderm has been mapped in the chick, arising principally from rostral streak at elongating streak stages, it is not known when this layer first becomes fully committed to its germ layer fate, an important issue to resolve in light of its critical role in subsequent patterning of the early embryo. Results Through gene expression screening of chick gastrula, we identified molecular markers of definitive endoderm restricted to rostral (Sox17 and caudal (Gata5/6 regions, suggesting that at least two subpopulations of definitive endodermal cells exist during ingression. We show (1 that presumptive mesoderm cells migrate to the middle layer and remain mesenchymal when transplanted to rostral primitive streak, and prospective endoderm cells enter the lower layer and become epithelial when transplanted to caudal primitive streak; and (2 that presumptive endoderm cells and mesoderm cells lose normal gene expression (Sox17 and Wnt8c, respectively when transplanted outside of their normal position of origin. Moreover, when rostral or caudal primitive streak segments are transplanted into rostral blastoderm isolates (RBIs, both types of transplants express Sox17 4–6 hours later–consistent with their new position, regardless of their presumptive germ layer origin–and prospective mesoderm transplants, which normally express Wnt8c, turn off expression, suggesting that signals within the rostral blastoderm induce endoderm gene expression, and repress mesoderm gene expression, during gastrulation. Conclusion Our results demonstrate that germ layer identity is fixed at the time populations of endoderm and mesoderm cells ingress through the primitive streak, whereas their gene expression patterns remain labile. In addition, our results show that

  15. Development of an embryonic skeletogenic mesenchyme lineage in a sea cucumber reveals the trajectory of change for the evolution of novel structures in echinoderms

    Directory of Open Access Journals (Sweden)

    McCauley Brenna S

    2012-08-01

    Full Text Available Abstract Background The mechanisms by which the conserved genetic “toolkit” for development generates phenotypic disparity across metazoans is poorly understood. Echinoderm larvae provide a great resource for understanding how developmental novelty arises. The sea urchin pluteus larva is dramatically different from basal echinoderm larval types, which include the auricularia-type larva of its sister taxon, the sea cucumbers, and the sea star bipinnaria larva. In particular, the pluteus has a mesodermally-derived larval skeleton that is not present in sea star larvae or any outgroup taxa. To understand the evolutionary origin of this structure, we examined the molecular development of mesoderm in the sea cucumber, Parastichopus parvimensis. Results By comparing gene expression in sea urchins, sea cucumbers and sea stars, we partially reconstructed the mesodermal regulatory state of the echinoderm ancestor. Surprisingly, we also identified expression of the transcription factor alx1 in a cryptic skeletogenic mesenchyme lineage in P. parvimensis. Orthologs of alx1 are expressed exclusively within the sea urchin skeletogenic mesenchyme, but are not expressed in the mesenchyme of the sea star, which suggests that alx1+ mesenchyme is a synapomorphy of at least sea urchins and sea cucumbers. Perturbation of Alx1 demonstrates that this protein is necessary for the formation of the sea cucumber spicule. Overexpression of the sea star alx1 ortholog in sea urchins is sufficient to induce additional skeleton, indicating that the Alx1 protein has not evolved a new function during the evolution of the larval skeleton. Conclusions The proposed echinoderm ancestral mesoderm state is highly conserved between the morphologically similar, but evolutionarily distant, auricularia and bipinnaria larvae. However, the auricularia, but not bipinnaria, also develops a simple skelotogenic cell lineage. Our data indicate that the first step in acquiring these novel

  16. Development of an embryonic skeletogenic mesenchyme lineage in a sea cucumber reveals the trajectory of change for the evolution of novel structures in echinoderms

    Science.gov (United States)

    2012-01-01

    Background The mechanisms by which the conserved genetic “toolkit” for development generates phenotypic disparity across metazoans is poorly understood. Echinoderm larvae provide a great resource for understanding how developmental novelty arises. The sea urchin pluteus larva is dramatically different from basal echinoderm larval types, which include the auricularia-type larva of its sister taxon, the sea cucumbers, and the sea star bipinnaria larva. In particular, the pluteus has a mesodermally-derived larval skeleton that is not present in sea star larvae or any outgroup taxa. To understand the evolutionary origin of this structure, we examined the molecular development of mesoderm in the sea cucumber, Parastichopus parvimensis. Results By comparing gene expression in sea urchins, sea cucumbers and sea stars, we partially reconstructed the mesodermal regulatory state of the echinoderm ancestor. Surprisingly, we also identified expression of the transcription factor alx1 in a cryptic skeletogenic mesenchyme lineage in P. parvimensis. Orthologs of alx1 are expressed exclusively within the sea urchin skeletogenic mesenchyme, but are not expressed in the mesenchyme of the sea star, which suggests that alx1+ mesenchyme is a synapomorphy of at least sea urchins and sea cucumbers. Perturbation of Alx1 demonstrates that this protein is necessary for the formation of the sea cucumber spicule. Overexpression of the sea star alx1 ortholog in sea urchins is sufficient to induce additional skeleton, indicating that the Alx1 protein has not evolved a new function during the evolution of the larval skeleton. Conclusions The proposed echinoderm ancestral mesoderm state is highly conserved between the morphologically similar, but evolutionarily distant, auricularia and bipinnaria larvae. However, the auricularia, but not bipinnaria, also develops a simple skelotogenic cell lineage. Our data indicate that the first step in acquiring these novel cell fates was to re-specify the

  17. The POU domain protein spg (pou2/Oct4) is essential for endoderm formation in cooperation with the HMG domain protein casanova.

    Science.gov (United States)

    Reim, Gerlinde; Mizoguchi, Takamasa; Stainier, Didier Y; Kikuchi, Yutaka; Brand, Michael

    2004-01-01

    The gastrulating vertebrate embryo develops three germlayers: ectoderm, mesoderm, and endoderm. Zebrafish endoderm differentiation starts with the activation of sox17 by casanova (cas). We report that spg (pou2/Oct4) is essential for endoderm formation. Embryos devoid of maternal and zygotic spg function (MZspg) lack endodermal precursors. Cell transplantations show that spg acts in early endodermal precursors, and cas mRNA-injection into MZspg embryos does not restore endoderm development. spg and cas together are both necessary and sufficient to activate endoderm development, and stimulate expression of a sox17 promoter-luciferase reporter. Endoderm and mesoderm derive from a common origin, mesendoderm. We propose that Spg and Cas commit mesendodermal precursors to an endodermal fate. The joint control of endoderm formation by spg and cas suggests that the endodermal germlayer may be a tissue unit with distinct genetic control, thus adding genetic support to the germlayer concept in metazoan development.

  18. Endoderm Generates Endothelial Cells during Liver Development

    Directory of Open Access Journals (Sweden)

    Orit Goldman

    2014-10-01

    Full Text Available Organogenesis requires expansion of the embryonic vascular plexus that migrates into developing organs through a process called angiogenesis. Mesodermal progenitors are thought to derive endothelial cells (ECs that contribute to both embryonic vasculogenesis and the subsequent organ angiogenesis. Here, we demonstrate that during development of the liver, which is an endoderm derivative, a subset of ECs is generated from FOXA2+ endoderm-derived fetal hepatoblast progenitor cells expressing KDR (VEGFR2/FLK-1. Using human and mouse embryonic stem cell models, we demonstrate that KDR+FOXA2+ endoderm cells developing in hepatic differentiation cultures generate functional ECs. This introduces the concept that ECs originate not exclusively from mesoderm but also from endoderm, supported in Foxa2 lineage-tracing mouse embryos by the identification of FOXA2+ cell-derived CD31+ ECs that integrate the vascular network of developing fetal livers.

  19. Logics and properties of a genetic regulatory program that drives embryonic muscle development in an echinoderm.

    Science.gov (United States)

    Andrikou, Carmen; Pai, Chih-Yu; Su, Yi-Hsien; Arnone, Maria Ina

    2015-07-28

    Evolutionary origin of muscle is a central question when discussing mesoderm evolution. Developmental mechanisms underlying somatic muscle development have mostly been studied in vertebrates and fly where multiple signals and hierarchic genetic regulatory cascades selectively specify myoblasts from a pool of naive mesodermal progenitors. However, due to the increased organismic complexity and distant phylogenetic position of the two systems, a general mechanistic understanding of myogenesis is still lacking. In this study, we propose a gene regulatory network (GRN) model that promotes myogenesis in the sea urchin embryo, an early branching deuterostome. A fibroblast growth factor signaling and four Forkhead transcription factors consist the central part of our model and appear to orchestrate the myogenic process. The topological properties of the network reveal dense gene interwiring and a multilevel transcriptional regulation of conserved and novel myogenic genes. Finally, the comparison of the myogenic network architecture among different animal groups highlights the evolutionary plasticity of developmental GRNs.

  20. Mouse Embryonic Fibroblasts (MEF) Exhibit a Similar but not Identical Phenotype to Bone Marrow Stromal Stem Cells (BMSC)

    DEFF Research Database (Denmark)

    Saeed, Hamid; Taipaleenmäki, Hanna; Aldahmash, Abdullah M

    2012-01-01

    Mouse embryonic fibroblasts have been utilized as a surrogate stem cell model for the postnatal bone marrow-derived stromal stem cells (BMSC) to study mesoderm-type cell differentiation e.g. osteoblasts, adipocytes and chondrocytes. However, no formal characterization of MEF phenotype has been....../tricalcium phosphate, in immune deficient mice. In conclusion, MEF contain a population of stem cells that behave in ex vivo and in vivo assays, similar but not identical, to BMSC. Due to their enhanced cell growth, they may represent a good alternative for BMSC in studying molecular mechanisms of stem cell commitment...... reported. Utilizing standard in vitro and in vivo assays we performed a side-by-side comparison of MEF and BMSC to determine their ability to differentiate into mesoderm-type cells. BMSC were isolated from 8-10 weeks old mouse bone marrow by plastic adherence. MEF were established by trypsin/EDTA digestion...

  1. Metastable primordial germ cell-like state induced from mouse embryonic stem cells by Akt activation

    Energy Technology Data Exchange (ETDEWEB)

    Yamano, Noriko [Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Kimura, Tohru, E-mail: tkimura@patho.med.osaka-u.ac.jp [Department of Pathology, Medical School, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Watanabe-Kushima, Shoko [Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Shinohara, Takashi [Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501 (Japan); Nakano, Toru, E-mail: tnakano@patho.med.osaka-u.ac.jp [Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Department of Pathology, Medical School, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)

    2010-02-12

    Specification to primordial germ cells (PGCs) is mediated by mesoderm-induction signals during gastrulation. We found that Akt activation during in vitro mesodermal differentiation of embryonic stem cells (ESCs) generated self-renewing spheres with differentiation states between those of ESCs and PGCs. Essential regulators for PGC specification and their downstream germ cell-specific genes were expressed in the spheres, indicating that the sphere cells had commenced differentiation to the germ lineage. However, the spheres did not proceed to spermatogenesis after transplantation into testes. Sphere cell transfer to the original feeder-free ESC cultures resulted in chaotic differentiation. In contrast, when the spheres were cultured on mouse embryonic fibroblasts or in the presence of ERK-cascade and GSK3 inhibitors, reversion to the ESC-like state was observed. These results indicate that Akt signaling promotes a novel metastable and pluripotent state that is intermediate to those of ESCs and PGCs.

  2. Mitosis-associated repression in development.

    Science.gov (United States)

    Esposito, Emilia; Lim, Bomyi; Guessous, Ghita; Falahati, Hanieh; Levine, Michael

    2016-07-01

    Transcriptional repression is a pervasive feature of animal development. Here, we employ live-imaging methods to visualize the Snail repressor, which establishes the boundary between the presumptive mesoderm and neurogenic ectoderm of early Drosophila embryos. Snail target enhancers were attached to an MS2 reporter gene, permitting detection of nascent transcripts in living embryos. The transgenes exhibit initially broad patterns of transcription but are refined by repression in the mesoderm following mitosis. These observations reveal a correlation between mitotic silencing and Snail repression. We propose that mitosis and other inherent discontinuities in transcription boost the activities of sequence-specific repressors, such as Snail. © 2016 Esposito et al.; Published by Cold Spring Harbor Laboratory Press.

  3. Radiologic findings in neurofibromatosis

    International Nuclear Information System (INIS)

    Kim, Dai Young; Jeon, Seok Chol; Lee, Kwan Se; Yeon, Kyung Mo; Choo, Dong Woon

    1979-01-01

    Neurofibromatosis is an uncommon but certainly not a rare hereditary disorder, probably of neuralcrest origin, involving not only neuroectoderm and mesoderm but also endoderm and characterized by cafe au lait spots and cutaneous and subcutaneous tumors, with secondary mesodermal defects responsible for protean osseous abnormalities and various manifestations in other systems. This paper is a study of confirmed 143 cases of neurofibromatosis collected for past 8 years. In this analysis, special attention was given to the selected 37 cases which showed abnormal findings on radiological examinations. Overall male to female ratio was 1 : 1.3. The most frequent kind of abnormalities was vertebral kyphoscoliosis in 12 cases. Among the more pathognomonic but uncommon abnormalities to neurofibromatosis, we experienced each 2 cases of lambdoid defect, pseudoarthrosis and renovascular hypertension, and 1 cases of sphenoid bone absence.

  4. Mesenchymal stem cell therapy for nonmusculoskeletal diseases: emerging applications.

    Science.gov (United States)

    Kuo, Tom K; Ho, Jennifer H; Lee, Oscar K

    2009-01-01

    Mesenchymal stem cells are stem/progenitor cells originated from the mesoderm and can different into multiple cell types of the musculoskeletal system. The vast differentiation potential and the relative ease for culture expansion have established mesenchymal stem cells as the building blocks in cell therapy and tissue engineering applications for a variety of musculoskeletal diseases, including repair of fractures and bone defects, cartilage regeneration, treatment of osteonecrosis of the femoral head, and correction of genetic diseases such as osteogenesis imperfect. However, research in the past decade has revealed differentiation potentials of mesenchymal stem cells beyond lineages of the mesoderm, suggesting broader applications than originally perceived. In this article, we review the recent developments in mesenchymal stem cell research with respect to their emerging properties and applications in nonmusculoskeletal diseases.

  5. Mechanical cell properties in germ layer progenitor migration during zebrafish gastrulation

    OpenAIRE

    Arboleda-Estudillo, Yoana

    2010-01-01

    Gastrulation leads to the formation of the embryonic germ layers, ectoderm, mesoderm and endoderm, and is the first key morphogenetic process that occurs in development. Gastrulation provides a unique developmental assay system in which to study cellular movements and rearrangements in vivo. The different cell movements occurring during gastrulation take place in a highly coordinated spatial and temporal manner, indicating that they must be controlled by a complex interplay of morphogene...

  6. Murine Mesenchymal Stem Cell Commitment to Differentiation is Regulated by Mitochondrial Dynamics

    OpenAIRE

    Forni, Maria Fernanda; Peloggia, Julia; Trudeau, Kyle; Shirihai, Orian; Kowaltowski, Alicia J.

    2015-01-01

    Mouse skin mesenchymal stem cells (msMSCs) are dermis CD105+CD90+CD73+CD29+CD34? mesodermal precursors which, after in vitro induction, undergo chondro, adipo and osteogenesis. Extensive metabolic reconfiguration has been found to occur during differentiation, and the bioenergetic status of a cell is known to be dependent on the quality and abundance of the mitochondrial population, which may be regulated by fusion and fission. However, little is known regarding the impact of mitochondrial dy...

  7. Structure and Function of the Splice Variants of TMPRSS2-ERG, a Prevalent Genomic Alteration in Prostate Cancer

    Science.gov (United States)

    2012-09-01

    also observe the co-expression of the Erg and Fli1 genes in both endo- thelial and mesodermal tissues, including urogenital tract and precartilaginous... urogenital regions [11]. All of the expression studies were carried out by using RT-PCR or in situ hybridization. How- ever, the protein expression and...negative for ERG. The ERG MAb did not show cross reactivity to FLI-1 in LNCaP cells infected with a FLI-1 adenovirus expression vector (Fig 1A

  8. Early diagnosis of regional odontodysplasia in an infant.

    Science.gov (United States)

    Canela, Alfredo Hiram Carrillo; Rezende, Karla Mayra Pinto E Carvalho; Benitez, Mirtha; Bönecker, Marcelo

    2012-03-01

    Regional odontodysplasia is a rare and significant dental malformation. It is a dental alteration of unknown etiology, involving both mesodermal and ectodermal dental components, which present clinical, radiographic, and histologic features. This article reports a clinical case of a 10-month-old child who was diagnosed with regional odontodysplasia in the maxilla, confirmed by radiographic examination, with a follow-up of 5 years. The clinical, radiographic, and histologic features were reviewed.

  9. VACTERL association with double-chambered left ventricle: A rare occurrence

    Directory of Open Access Journals (Sweden)

    Abdulla Al-Farqani

    2013-01-01

    Full Text Available VACTERL association is a non-random association of birth defects of unknown etiology derived from structures of embryonic mesoderm. The common cardiac defects seen with VACTERL association are ventricular septal defects, atrial septal defects, and tetralogy of Fallot. We present a 2-year-old child with VACTERL association in whom we detected double-chambered left ventricle on transthoracic echocardiography.

  10. Prune Belly Syndrome Associated with Full Spectrum of VACTERL in a New Born.

    Science.gov (United States)

    Younous, Said; Zarrouki, Youssef; Boutbaoucht, Mustapha; Mouaffak, Youssef; El Idrissi, Kawtar Ennour; Aboussair, Nissrine; Saiad, Mohammed O

    2012-01-01

    Prune belly syndrome (PBS) is a rare congenital anomaly of uncertain etiology. Many associations of PBS with other malformations were previously reported, but only few cases of the association with VACTERL have been described. We report a rare case of a Moroccan new born with PBS and complete VACTERL association. The cause of this association is still unknown, but a common etiology is possible, especially when for the two syndromes, a defect in mesodermal differentiation, in early first trimester, has been suggested.

  11. Ureteropelvic junction obstruction caused by Fibroepithelial polyps in children

    OpenAIRE

    Knoblich, Maria; Vital, Vanda; Cardoso, Dinorah; Alves, Fátima; Mota, Filipe; Casella, Paolo

    2017-01-01

    Fibroepithelial polyps are extremely rare benign tumors arising from mesodermal tissue in the ureteral wall in children, that can cause ureteropelvic junction obstruction. In this report, we present an 11‐year‐old boy complaining of left intermitent lumbar pain related with ipsilateral hydronephrosis. Surgical exploration revealed several endoluminal polyps located at the ureteropelvic junction, obstructing the lumen of the ureter. Standard treatment consists in resection of the affected uret...

  12. Sonic hedgehog promotes somitic chondrogenesis by altering the cellular response to BMP signaling

    OpenAIRE

    Murtaugh, L. Charles; Chyung, Jay H.; Lassar, Andrew B.

    1999-01-01

    Previous work has indicated that signals from the floor plate and notochord promote chondrogenesis of the somitic mesoderm. These tissues, acting through the secreted signaling molecule Sonic hedgehog (Shh), appear to be critical for the formation of the sclerotome. Later steps in the differentiation of sclerotome into cartilage may be independent of the influence of these axial tissues. Although the signals involved in these later steps have not yet been pinpointed, there is substantial evid...

  13. Hyperglycemia-Induced Vasculopathy in the Murine Vitelline Vasculature : Correlation with PECAM-1/CD31 Tyrosine Phosphorylation State

    OpenAIRE

    Pinter, Emese; Mahooti, Sepi; Wang, Yi; Imhof, Beat A.; Madri, Joseph A.

    1999-01-01

    Maternal diabetes mellitus is associated with an increased incidence of congenital abnormalities as well as embryonic and perinatal lethality. In particular, a wide range of cardiovascular abnormalities have been noted in children of diabetic mothers and in the offspring of diabetic animals. The vascular system is the first organ system to develop in the embryo and is critical for normal organogenesis. The organization of mesodermal cells into endothelial and hematopoietic cells and into a co...

  14. Signaling molecules, transcription growth factors and other regulators revealed from in-vivo and in-vitro models for the regulation of cardiac development.

    Science.gov (United States)

    Meganathan, Kesavan; Sotiriadou, Isaia; Natarajan, Karthick; Hescheler, Jürgen; Sachinidis, Agapios

    2015-03-15

    Several in-vivo heart developmental models have been applied to decipher the cardiac developmental patterning encompassing early, dorsal, cardiac and visceral mesoderm as well as various transcription factors such as Gata, Hand, Tin, Dpp, Pnr. The expression of cardiac specific transcription factors, such as Gata4, Tbx5, Tbx20, Tbx2, Tbx3, Mef2c, Hey1 and Hand1 are of fundamental significance for the in-vivo cardiac development. Not only the transcription factors, but also the signaling molecules involved in cardiac development were conserved among various species. Enrichment of the bone morphogenic proteins (BMPs) in the anterior lateral plate mesoderm is essential for the initiation of myocardial differentiation and the cardiac developmental process. Moreover, the expression of a number of cardiac transcription factors and structural genes initiate cardiac differentiation in the medial mesoderm. Other signaling molecules such as TGF-beta, IGF-1/2 and the fibroblast growth factor (FGF) play a significant role in cardiac repair/regeneration, ventricular heart development and specification of early cardiac mesoderm, respectively. The role of the Wnt signaling in cardiac development is still controversial discussed, as in-vitro results differ dramatically in relation to the animal models. Embryonic stem cells (ESC) were utilized as an important in-vitro model for the elucidation of the cardiac developmental processes since they can be easily manipulated by numerous signaling molecules, growth factors, small molecules and genetic manipulation. Finally, in the present review the dynamic role of the long noncoding RNA and miRNAs in the regulation of cardiac development are summarized and discussed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Oculocutaneous Albinism associated with Axenfeld’s Anomaly

    Science.gov (United States)

    Keshav, B R; Mohammed, Mahmood J; Mahmood, Nasir

    2010-01-01

    Oculocutaneous albinism and anterior mesodermal dysgenesis are well-known heritable conditions, but their occurrence in association has only been rarely reported. We present cases of three siblings of a family with identical presentation suggesting that this association may be more than just a coincidence. This association is worth noting, as this could be one of the causes of ocular morbidity and poor vision in oculocutaneous albinism. PMID:21509091

  16. An E-Cadherin-mediated hitchhiking mechanism for C. elegans germ cell internalization during gastrulation

    OpenAIRE

    Chihara, Daisuke; Nance, Jeremy

    2011-01-01

    Gastrulation movements place endodermal precursors, mesodermal precursors and primordial germ cells (PGCs) into the interior of the embryo. Somatic cell gastrulation movements are regulated by transcription factors that also control cell fate, coupling cell identity and position. By contrast, PGCs in many species are transcriptionally quiescent, suggesting that they might use alternative gastrulation strategies. Here, we show that C. elegans PGCs internalize by attaching to internal endoderma...

  17. Bmp4 is required for the generation of primordial germ cells in the mouse embryo

    OpenAIRE

    Lawson, Kirstie A.; Dunn, N. Ray; Roelen, Bernard A.J.; Zeinstra, Laura M.; Davis, Angela M.; Wright, Christopher V.E.; Korving, Jeroen P.W.F.M.; Hogan, Brigid L.M.

    1999-01-01

    In many organisms the allocation of primordial germ cells (PGCs) is determined by the inheritance of maternal factors deposited in the egg. However, in mammals, inductive cell interactions are required around gastrulation to establish the germ line. Here, we show that Bmp4 homozygous null embryos contain no PGCs. They also lack an allantois, an extraembryonic mesodermal tissue derived, like the PGCs, from precursors in the proximal epiblast. Heterozygotes have fewer PGCs than normal, due to a...

  18. Derivation of the human embryonic stem cell line RCe008-A (RC-4

    Directory of Open Access Journals (Sweden)

    P.A. De Sousa

    2016-05-01

    Full Text Available The human embryonic stem cell line RCe008-A (RC-4 was derived from a blastocyst voluntarily donated as unsuitable and surplus to fertility requirements following ethics committee approved informed consent under licence from the UK Human Fertilisation and Embryology Authority. The cell line shows normal pluripotency marker expression and differentiation to ectoderm and mesoderm in vitro. It has a mixed 46XX/45X female karyotype and microsatellite PCR identity and blood group typing data is available.

  19. Intratesticular and intraovarian epidermoid inclusion cysts: report of two cases

    Directory of Open Access Journals (Sweden)

    Guilherme José Morgan

    2013-04-01

    Full Text Available Two rare cases of intragonadal epidermoid inclusion cysts are described. Their etiology remains controversial and a possible hypothesis is monodermal abortive teratomas, with no mesodermal and endodermal components. As the ultrasound test results were inconclusive, it became difficult to rule out the possibility of neoplasm. Therefore, patients were submitted to radical therapy. The definitive diagnosis for both cases was provided by the anatomopathological examination.

  20. Temporal and contextual orchestration of cardiac fate by WNT-BMP synergy and threshold.

    Science.gov (United States)

    Verma, Mahesh K; Lenka, Nibedita

    2010-08-01

    Cardiomyogenic development proceeds with a cascade of intricate signalling events that operate in a temporo-spatial fashion to specify cardiac cell fate during early embryogenesis. In fact, conflicting reports exist regarding the role of Wnt/β-catenin signalling during cardiomyogenesis. Here, we describe a dose-dependent and temporal effect of Wnt/β-catenin signalling on in vitro cardiomyogenesis using embryonic stem cells (ESCs) as a model system. We could demonstrate that canonical Wnt activation during early stage of differentiation either through ligand or by GSK3β inhibition helped in maintaining Oct4 and Nanog expressions, and in parallel, it promoted mesoderm and endoderm inductions. In contrast, it led to attenuation in cardiomyogenesis that was reversed by moderate concentration of DKK1, but not soluble Fz8. However, higher DKK1 could also block cardiomyogenesis, suggesting thereby governance of a particular signalling threshold underlying this developmental event. Interestingly, Wnt signalling activation at early stage modulated BMP4 expression in a stage-specific manner. Wnt activation, synchronized with BMP4 and brachyury up-regulation at early stage, correlated well with mesoderm induction. Conversely, Wnt activation led to BMP4 and Wnt5a down-regulation at late stage culminating in cardiomyogenic attenuation. Our findings suggested the existence of precise regulatory machinery with context-dependent role of Wnt for fine tuning mesoderm induction and its derivatives, through establishment of Wnt gradient during ESCs' differentiation. Moreover, contrary to mere activation/inhibition, a specific threshold of Wnt and BMP and their synergy seemed necessary for providing the guiding cues in orchestrating mesoderm induction and subsequent cardiomyogenesis. © 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  1. Putative histogenesis of post nasal angiofibroma

    OpenAIRE

    Mishra, S. C.

    2000-01-01

    Inspite of the histological resemblance, these tumefactions do not behave like true neoplasms. Harma (1959) believed their histogenesis from angioblasls. Taxy (1977) regards the fihroblasts as the main stroma cell which has resemblences like those of the granulation tissues, and hence appear to be hybrid fihroblasts. Vascular and fibrous element could be produced by any mesodermal “stem cell” (Shenoi. 1989). Therefore both fihroblasts and angioblasts may be inter-convertible.

  2. Cell-Autonomous and Non-Cell-Autonomous Roles for Irf6 during Development of the Tongue

    Science.gov (United States)

    Goudy, Steven; Angel, Peggi; Jacobs, Britni; Hill, Cynthia; Mainini, Veronica; Smith, Arianna L.; Kousa, Youssef A.; Caprioli, Richard; Prince, Lawrence S.; Baldwin, Scott; Schutte, Brian C.

    2013-01-01

    Interferon regulatory factor 6 (IRF6) encodes a highly conserved helix-turn-helix DNA binding protein and is a member of the interferon regulatory family of DNA transcription factors. Mutations in IRF6 lead to isolated and syndromic forms of cleft lip and palate, most notably Van der Woude syndrome (VWS) and Popliteal Ptyerigium Syndrome (PPS). Mice lacking both copies of Irf6 have severe limb, skin, palatal and esophageal abnormalities, due to significantly altered and delayed epithelial development. However, a recent report showed that MCS9.7, an enhancer near Irf6, is active in the tongue, suggesting that Irf6 may also be expressed in the tongue. Indeed, we detected Irf6 staining in the mesoderm-derived muscle during development of the tongue. Dual labeling experiments demonstrated that Irf6 was expressed only in the Myf5+ cell lineage, which originates from the segmental paraxial mesoderm and gives rise to the muscles of the tongue. Fate mapping of the segmental paraxial mesoderm cells revealed a cell-autonomous Irf6 function with reduced and poorly organized Myf5+ cell lineage in the tongue. Molecular analyses showed that the Irf6−/− embryos had aberrant cytoskeletal formation of the segmental paraxial mesoderm in the tongue. Fate mapping of the cranial neural crest cells revealed non-cell-autonomous Irf6 function with the loss of the inter-molar eminence. Loss of Irf6 function altered Bmp2, Bmp4, Shh, and Fgf10 signaling suggesting that these genes are involved in Irf6 signaling. Based on these data, Irf6 plays important cell-autonomous and non-cell-autonomous roles in muscular differentiation and cytoskeletal formation in the tongue. PMID:23451037

  3. [Novel concepts in biology of diffuse endocrine system: results and future investigations].

    Science.gov (United States)

    Iaglov, V V; Iaglova, N V

    2012-01-01

    Diffuse endocrine system is a largest part of endocrine system of vertebrates. Recend findings showed that DES-cells are not neuroectodermal but have ectodermal, mesodermal, and entodermal ontogeny. The article reviews novel concept of diffuse endocrine system anatomy and physiology, functional role of DES hormones and poorly investigated aspects like DES-cell morphology, hormones secretion in normal and pathologic conditions. Further research of diffuse endocrine system has a great significance for biochemistry, morphology, and clinical medicine.

  4. Experiment list: SRX100887 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available raembryonic mesoderm, trophectoderm|Description=chorion cells (outermost of two fetal membranes), fetal membranes... were collected from women who underwent planned cesarean delivery at term, before labor and without rupture of membranes...an || cell description=chorion cells (outermost of two fetal membranes), fetal membranes were collected from... women who underwent planned cesarean delivery at term, before labor and without rupture of membranes. || ce

  5. Razvoj srca: Development of the heart:

    OpenAIRE

    Petrovič, Danijel; Zorc, Marjeta

    2003-01-01

    The cardiovascular system is the first major organ system that develops and starts functioning in a growing embryo, because diffusion alone can no longer supply it with enough oxygen and nutrients. The heart forms at the end of the third week from the splanchnic mesoderm as a horseshoe-shaped primordium. Bilateral cardiac tubes fuse in the midline, and the fused cardiac tube undergoes further S-shaped bending. The heart increases in size, and several chambers (two atria and two ventricles) an...

  6. Expression of the zic1, zic2, zic3, and zic4 genes in early chick embryos

    Directory of Open Access Journals (Sweden)

    Merzdorf Christa S

    2010-06-01

    Full Text Available Abstract Background The zic genes encode a family of transcription factors with important roles during early development. Since little is known about zic gene expression in chick embryos, we have characterized the expression patterns of the zic1, zic2, zic3, and zic4 (zic1-4 genes during neurulation and somitogenesis. Findings We used in situ hybridization to analyze the expression patterns of the zic1-4 genes during early chick development (HH stages 7-19. The zic1-3 genes showed both overlapping and gene-specific expression patterns along the length of the dorsal neural tube and in the dorsal parts of the somites. In addition, unique expression domains of zic genes included: zic2 in the neural plate, periotic mesoderm and limb buds; zic3 in the paraxial mesoderm surrounding the neural plate, in presomitic mesoderm and in the most recently formed epithelial somites; zic2 and zic3 in developing eyes. zic4 expression was limited to dorsal fore- and midbrain regions and, unlike the expression of the zic1-3 genes, zic4 expression was not detected in the hindbrain and trunk. This was in contrast to more extensive zic4 expression in other vertebrates. Conclusions The zic1-3 genes were expressed in both overlapping and unique domains within the neural tube, somites and other ectoderm and mesoderm-derived structures in the future head and trunk. zic4 expression, however, was limited to dorso-anterior regions of the future brain. This is the first comprehensive study of zic1-4 gene expression in chick embryos during neurulation and somitogenesis.

  7. Primary Pulmonary Leiomyoma in a Male

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    Ail Kutluk

    2016-07-01

    Full Text Available Primary pulmonary leiomyoma of the lung is benign in nature and is one of the rarest tumors of mesodermal origin. Because of the increasing number of routine chest roentgenograms, these lesions are being discovered more frequently. Treatment is by conservative surgical resection and carries a favorable prognosis. We presented a 30-year-old patient with expectoration cough and night sweats who undergone resection due to a mass in left lower lobe and diagnosed primary pulmonary leiomyoma.

  8. Inhibition of Rho kinase regulates specification of early differentiation events in P19 embryonal carcinoma stem cells.

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    Roman J Krawetz

    Full Text Available The Rho kinase pathway plays a key role in many early cell/tissue determination events that take place in embryogenesis. Rho and its downstream effector Rho kinase (ROCK play pivotal roles in cell migration, apoptosis (membrane blebbing, cell proliferation/cell cycle, cell-cell adhesion and gene regulation. We and others have previously demonstrated that inhibition of ROCK blocks endoderm differentiation in embryonal carcinoma stem cells, however, the effect of ROCK inhibition on mesoderm and ectoderm specification has not been fully examined. In this study, the role of ROCK within the specification and differentiation of all three germ layers was examined.P19 cells were treated with the specific ROCK inhibitor Y-27623, and increase in differentiation efficiency into neuro-ectodermal and mesodermal lineages was observed. However, as expected a dramatic decrease in early endodermal markers was observed when ROCK was inhibited. Interestingly, within these ROCK-inhibited RA treated cultures, increased levels of mesodermal or ectodermal markers were not observed, instead it was found that the pluripotent markers SSEA-1 and Oct-4 remained up-regulated similar to that seen in undifferentiated cultures. Using standard and widely accepted methods for reproducible P19 differentiation into all three germ layers, an enhancement of mesoderm and ectoderm differentiation with a concurrent loss of endoderm lineage specification was observed with Y-27632 treatment. Evidence would suggest that this effect is in part mediated through TGF-β and SMAD signaling as ROCK-inhibited cells displayed aberrant SMAD activation and did not return to a 'ground' state after the inhibition had been removed.Given this data and the fact that only a partial rescue of normal differentiation capacity occurred when ROCK inhibition was alleviated, the effect of ROCK inhibition on the differentiation capacity of pluripotent cell populations should be further examined to elucidate the

  9. Exogenous Sonic hedgehog protein does not rescue cultured intestine from atresia formation.

    Science.gov (United States)

    Reeder, Amy L; Zaremba, Krzysztof M; Liebl, Rebeca M; Kowalkowski, Anna; Nichol, Peter F

    2014-03-01

    The mechanism of intestinal atresia formation remains undefined. Atresia in fibroblast growth factor receptor 2IIIb (Fgfr2IIIb(-/-)) mutant mouse embryos is preceded by endodermal apoptosis and involution of the surrounding mesoderm. We have observed that involution of the atretic segment is preceded by the downregulation of Sonic hedgehog (SHH) in the endoderm, which is a critical organizer of the intestinal mesoderm. We hypothesized that supplementation of Fgfr2IIIb(-/-) intestinal tracts with exogenous SHH protein before atresia formation would prevent involution of the mesoderm and rescue normal intestinal development. In situ hybridization was performed on control and Fgfr2IIIb(-/-) intestinal tracts for Shh or forkhead box protein F1 (FoxF1) between embryonic (E) day 11.5 and E12.0. Control and Fgfr2IIIb(-/-) intestinal tracts were harvested at E10.5 and cultured in media supplemented with fibroblast growth factor (FGF) 10 + SHH, or FGF10 with a SHH-coated bead. In situ hybridization was performed at E12.5 for Foxf1. SHH and Foxf1 expression were downregulated during intestinal atresia formation. Media containing exogenous FGF10 + SHH did not prevent colonic atresia formation (involution). A SHH protein point source bead did induce Foxf1 expression in controls and mutants. Shh and Foxf1 expression are disrupted in atresia formation of distal colon, thereby serving as potential markers of atretic events. Application of exogenous SHH (in media supplement or as a point source bead) is sufficient to induce Foxf1 expression, but insufficient to rescue development of distal colonic mesoderm in Fgfr2IIIb(-/-) mutant embryos. Shh signal disruption is not the critical mechanism by which loss of Fgfr2IIIb function results in atresia formation. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Neurofibromatosis and multiple non-ossifying fibromas

    International Nuclear Information System (INIS)

    Erlemann, R.; Fischedick, A.R.; Edel, G.; Peters, P.E.; Galanski, M.; Muenster Univ.; Medizinische Hochschule Hannover

    1987-01-01

    Three patients with a combination of neurofibromatosis and multiple non-ossifying fibromas are presented. All patients possessed multiple osteolytic lesions with sclerotic margins, resembling non-ossifying fibromas. Two patients showed similar lesions in additional localizations. In two patients, non-ossifying fibroma was histologically verified. The simultaneous occurrence of neurofibromatosis and multiple non-ossifying fibromas can possibly be put down to a generalized mesodermal dysplasia. However, the definite explanation is unknown. (orig.) [de

  11. Ruptured profunda femoris aneurysm secondary to neurofibromatosis: vascular involvement in an unusual location.

    Science.gov (United States)

    Emrecan, Bilgin; Onem, Gokhan; Susam, Ibrahim

    2010-01-01

    Neurofibromatosis is an autosomal dominant genetic disease characterized by abnormal growth that involves tissues of mesodermal and neuroectodermal origin. Aneurysms are rarely seen in peripheral arteries. This report presents a case of ruptured arterial aneurysm secondary to neurofibromatosis; the lesion occurred in the profunda femoris artery, a highly unusual location. Treatment of patients with ruptured arterial aneurysm secondary to neurofibromatosis may be interventional or surgical. In this case, a surgical approach was successful.

  12. Morphological and dynamic MR evaluation of a giant spontaneous vertebrovertebral fistula during endovascular therapy

    International Nuclear Information System (INIS)

    McGlade, C.; Lufkin, R.; Vinuela, F.; Dion, J.; Lylyck, P.; Bentson, J.; Martin, N.

    1989-01-01

    A case of verbro-vertebral fistula in a patient with neurofibromatosis is presented with emphasis on magnetic resonance (MR) evaluation and integration with endovascular therapy. Vascular involvement is a known complication of neurofibromatosis ranging from intimal proliferation causing arterial narrowing, development of small aneurysms, to spontaneous fistulas probably secondary to mesodermal dysplasia. This case report illustrates the latter and portrays a role for MR in diagnosis and follow-up during therapeutic measures. (author). 14 refs.; 3 figs

  13. Bevacizumab Modulation of the Interaction Between the MCF-7 Cell Line and the Chick Embryo Chorioallantoic Membrane

    OpenAIRE

    COMŞA, ŞERBAN; POPESCU, ROXANA; AVRAM, ŞTEFANA; CEAUȘU, RALUCA AMALIA; CÎMPEAN, ANCA MARIA; RAICA, MARIUS

    2017-01-01

    Aim: To evaluate the interaction between MCF-7 breast cancer cells and the chick embryo chorioallantoic membrane (CAM) and the ability of bevacizumab to modulate this process. Materials and Methods: We implanted MCF-7 cells onto CAM and repeatedly added bevacizumab to a subset of eggs. We then evaluated the morphological and immunohistochemical profiles of CAM and MCF-7. Results: MCF-7 cells entered the mesoderm and stimulated the mesenchymal cells to acquire vasculogenic and myofibroblastoid...

  14. A Giant Pedunculated Urothelial Polyp Mimicking Bladder Mass in a Child: A Rare Case

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    Mehmet Kaba

    2014-01-01

    Full Text Available Ureteral fibroepithelial polyps are rarely seen benign tumors with mesodermal origin. These polyps can involve kidney, pelvis, ureter, bladder, and urethra. The most common symptoms are hematuria and flank pain. The choice of treatment is either endoscopic or surgical resection of polyp by sparing kidney. Here, we presented a pediatric case with giant, fibroepithelial polyp that mimics bladder tumor, originating from middle segment of the ureter.

  15. ABCC5 is required for cAMP-mediated hindgut invagination in sea urchin embryos.

    Science.gov (United States)

    Shipp, Lauren E; Hill, Rose Z; Moy, Gary W; Gökırmak, Tufan; Hamdoun, Amro

    2015-10-15

    ATP-binding cassette (ABC) transporters are evolutionarily conserved proteins that pump diverse substrates across membranes. Many are known to efflux signaling molecules and are extensively expressed during development. However, the role of transporters in moving extracellular signals that regulate embryogenesis is largely unexplored. Here, we show that a mesodermal ABCC (MRP) transporter is necessary for endodermal gut morphogenesis in sea urchin embryos. This transporter, Sp-ABCC5a (C5a), is expressed in pigment cells and their precursors, which are a subset of the non-skeletogenic mesoderm (NSM) cells. C5a expression depends on Delta/Notch signaling from skeletogenic mesoderm and is downstream of Gcm in the aboral NSM gene regulatory network. Long-term imaging of development reveals that C5a knockdown embryos gastrulate, but ∼90% develop a prolapse of the hindgut by the late prism stage (∼8 h after C5a protein expression normally peaks). Since C5a orthologs efflux cyclic nucleotides, and cAMP-dependent protein kinase (Sp-CAPK/PKA) is expressed in pigment cells, we examined whether C5a could be involved in gastrulation through cAMP transport. Consistent with this hypothesis, membrane-permeable pCPT-cAMP rescues the prolapse phenotype in C5a knockdown embryos, and causes archenteron hyper-invagination in control embryos. In addition, the cAMP-producing enzyme soluble adenylyl cyclase (sAC) is expressed in pigment cells, and its inhibition impairs gastrulation. Together, our data support a model in which C5a transports sAC-derived cAMP from pigment cells to control late invagination of the hindgut. Little is known about the ancestral functions of ABCC5/MRP5 transporters, and this study reveals a novel role for these proteins in mesoderm-endoderm signaling during embryogenesis. © 2015. Published by The Company of Biologists Ltd.

  16. Endoglin potentiates nitric oxide synthesis to enhance definitive hematopoiesis

    Science.gov (United States)

    Nasrallah, Rabab; Knezevic, Kathy; Thai, Thuan; Thomas, Shane R.; Göttgens, Berthold; Lacaud, Georges; Kouskoff, Valerie; Pimanda, John E.

    2015-01-01

    ABSTRACT During embryonic development, hematopoietic cells develop by a process of endothelial-to hematopoietic transition of a specialized population of endothelial cells. These hemogenic endothelium (HE) cells in turn develop from a primitive population of FLK1+ mesodermal cells. Endoglin (ENG) is an accessory TGF-β receptor that is enriched on the surface of endothelial and hematopoietic stem cells and is also required for the normal development of hemogenic precursors. However, the functional role of ENG during the transition of FLK1+ mesoderm to hematopoietic cells is ill defined. To address this we used a murine embryonic stem cell model that has been shown to mirror the temporal emergence of these cells in the embryo. We noted that FLK1+ mesodermal cells expressing ENG generated fewer blast colony-forming cells but had increased hemogenic potential when compared with ENG non-expressing cells. TIE2+/CD117+ HE cells expressing ENG also showed increased hemogenic potential compared with non-expressing cells. To evaluate whether high ENG expression accelerates hematopoiesis, we generated an inducible ENG expressing ES cell line and forced expression in FLK1+ mesodermal or TIE2+/CD117+ HE cells. High ENG expression at both stages accelerated the emergence of CD45+ definitive hematopoietic cells. High ENG expression was associated with increased pSMAD2/eNOS expression and NO synthesis in hemogenic precursors. Inhibition of eNOS blunted the ENG induced increase in definitive hematopoiesis. Taken together, these data show that ENG potentiates the emergence of definitive hematopoietic cells by modulating TGF-β/pSMAD2 signalling and increasing eNOS/NO synthesis. PMID:25979706

  17. Endoglin potentiates nitric oxide synthesis to enhance definitive hematopoiesis

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    Rabab Nasrallah

    2015-07-01

    Full Text Available During embryonic development, hematopoietic cells develop by a process of endothelial-to hematopoietic transition of a specialized population of endothelial cells. These hemogenic endothelium (HE cells in turn develop from a primitive population of FLK1+ mesodermal cells. Endoglin (ENG is an accessory TGF-β receptor that is enriched on the surface of endothelial and hematopoietic stem cells and is also required for the normal development of hemogenic precursors. However, the functional role of ENG during the transition of FLK1+ mesoderm to hematopoietic cells is ill defined. To address this we used a murine embryonic stem cell model that has been shown to mirror the temporal emergence of these cells in the embryo. We noted that FLK1+ mesodermal cells expressing ENG generated fewer blast colony-forming cells but had increased hemogenic potential when compared with ENG non-expressing cells. TIE2+/CD117+ HE cells expressing ENG also showed increased hemogenic potential compared with non-expressing cells. To evaluate whether high ENG expression accelerates hematopoiesis, we generated an inducible ENG expressing ES cell line and forced expression in FLK1+ mesodermal or TIE2+/CD117+ HE cells. High ENG expression at both stages accelerated the emergence of CD45+ definitive hematopoietic cells. High ENG expression was associated with increased pSMAD2/eNOS expression and NO synthesis in hemogenic precursors. Inhibition of eNOS blunted the ENG induced increase in definitive hematopoiesis. Taken together, these data show that ENG potentiates the emergence of definitive hematopoietic cells by modulating TGF-β/pSMAD2 signalling and increasing eNOS/NO synthesis.

  18. Tendon and Ligament Regeneration and Repair: Clinical Relevance and Developmental Paradigm

    OpenAIRE

    Yang, Guang; Rothrauff, Benjamin B.; Tuan, Rocky S.

    2013-01-01

    Tendon and ligament (T/L) are dense connective tissues connecting bone to muscle and bone to bone, respectively. Similar to other musculoskeletal tissues, T/L arise from the somitic mesoderm, but they are derived from a recently discovered somitic compartment, the syndetome. The adjacent sclerotome and myotome provide inductive signals to the interposing syndetome, thereby upregulating the expression of the transcription factor Scleraxis, which in turn leads to further tenogenic and ligamento...

  19. REGIONAL ODONTODYSPLASIA: CASE REPORT

    OpenAIRE

    Magalh?es, Ana Carolina; Pessan, Juliano Pelim; Cunha, Robson Frederico; Delbem, Alberto Carlos Botazzo

    2007-01-01

    Regional odontodysplasia (RO) is a rare developmental anomaly involving both mesodermal and ectodermal dental components in a group of contiguous teeth. It affects the primary and permanent dentitions in the maxilla and mandible or both jaws. Generally it is localized in only one arch. The etiology of this dental anomaly is uncertain. Clinically, affected teeth have an abnormal morphology, are soft on probing and typically discolored, yellow or yellowish-brown. Radiographically, the affected ...

  20. Crabnioficial Development and the Evolution of the Vertebrates : the Old Problems on a New Background

    OpenAIRE

    Shigeru, Kuratani; Laboratory for Evolutionary Morphology Center for Developmental Biology (CDB), RIKEN

    2005-01-01

    Based on recent advances in experimental embryology and molecular genetics, the morphogenetic program for the vertebrate cranium is summarized and several unanswered classical problems are reviewed. In particular, the presence of mesodermal segmentation in the head, the homology of the trabecular cartilage, and the origin of the dermal skull roof are discussed. The discovery of the neural-crest-derived ectomesenchyme and the roles of the homeobox genes have allowed the classical concept of he...

  1. Development, triploblastism, physics of wetting and the Cambrian explosion.

    Science.gov (United States)

    Fleury, Vincent

    2013-09-01

    The Cambrian explosion is characterized by the sudden outburst of organized animal plans, which occurred circa 530 M years ago. Around that time, many forms of animal life appeared, including several which have since disappeared. There is no general consensus about "why" this happened, and why it had any form of suddenness. However, all organized animal plans share a common feature: they are triploblastic, i.e., composed of 3 layers of tissue, endoderm, ectoderm and mesoderm. I show here that, within simple hypotheses, the formation of the mesoderm has intrinsically a physical exponential dynamics, leading rapidly to triploblastism, and eventually, to animal formation. A novel physico-mathematical framework including epithelium-mesenchyme transition, visco-elastic constitutive equations, and conservation laws, is presented which allows one to describe gastrulation as a self-wetting phenomenon of a soft solid onto itself. This phenomenon couples differentiation and migration during gastrulation, and leads in a closed form to an exponential scaling law for the formation of the mesoderm. Therefore, the Cambrian explosion might have started, actually, by a true viscoelastic "explosion": the exponential run-away of mesenchymal cells.

  2. Multiple cranial organ defects after conditionally knocking out Fgf10 in the neural crest

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    Tathyane H.N. Teshima

    2016-10-01

    Full Text Available Fgf10 is necessary for the development of a number of organs that fail to develop or are reduced in size in the null mutant. Here we have knocked out Fgf10 specifically in the neural crest driven by Wnt1cre. The Wnt1creFgf10fl/fl mouse phenocopies many of the null mutant defects, including cleft palate, loss of salivary glands and ocular glands, highlighting the neural crest origin of the Fgf10 expressing mesenchyme surrounding these organs. In contrast tissues such as the limbs and lungs, where Fgf10 is expressed by the surrounding mesoderm, were unaffected, as was the pituitary gland where Fgf10 is expressed by the neuroepithelium. The circumvallate papilla of the tongue formed but was hypoplastic in the conditional and Fgf10 null embryos, suggesting that other sources of FGF can compensate in development of this structure. The tracheal cartilage rings showed normal patterning in the conditional knockout, indicating that the source of Fgf10 for this tissue is mesodermal, which was confirmed using Wnt1cre-dtTom to lineage trace the boundary of the neural crest in this region. The thyroid, thymus and parathyroid glands surrounding the trachea were present but hypoplastic in the conditional mutant, indicating that a neighbouring source of mesodermal Fgf10 might be able to partially compensate for loss of neural crest derived Fgf10.

  3. Wnt signaling positively regulates endothelial cell fate specification in the Fli1a-positive progenitor population via Lef1.

    Science.gov (United States)

    Hübner, Kathleen; Grassme, Kathrin S; Rao, Jyoti; Wenke, Nina K; Zimmer, Cordula L; Korte, Laura; Mu Ller, Katja; Sumanas, Saulius; Greber, Boris; Herzog, Wiebke

    2017-10-01

    During vertebrate embryogenesis, vascular endothelial cells (ECs) and primitive erythrocytes become specified within close proximity in the posterior lateral plate mesoderm (LPM) from a common progenitor. However, the signaling cascades regulating the specification into either lineage remain largely elusive. Here, we analyze the contribution of β-catenin dependent Wnt signaling to EC and erythrocyte specification during zebrafish embryogenesis. We generated novel β-catenin dependent Wnt signaling reporters which, by using destabilized fluorophores (Venus-Pest, dGFP), specifically allow us to detect Wnt signaling responses in narrow time windows as well as in spatially restricted domains, defined by Cre recombinase expression (Tg(axin2 BAC :Venus-Pest) mu288 ; Tg(14TCF:loxP-STOP-loxP-dGFP) mu202 ). We therefore can detect β-catenin dependent Wnt signaling activity in a subset of the Fli1a-positive progenitor population. Additionally, we show that mesodermal Wnt3a-mediated signaling via the transcription factor Lef1 positively regulates EC specification (defined by kdrl expression) at the expense of primitive erythrocyte specification (defined by gata1 expression) in zebrafish embryos. Using mesoderm derived from human embryonic stem cells, we identified the same principle of Wnt signaling dependent EC specification in conjunction with auto-upregulation of LEF1. Our data indicate a novel role of β-catenin dependent Wnt signaling in regulating EC specification during vasculogenesis. Copyright © 2017. Published by Elsevier Inc.

  4. Evolution and development of the vertebrate neck.

    Science.gov (United States)

    Ericsson, Rolf; Knight, Robert; Johanson, Zerina

    2013-01-01

    Muscles of the vertebrate neck include the cucullaris and hypobranchials. Although a functional neck first evolved in the lobe-finned fishes (Sarcopterygii) with the separation of the pectoral/shoulder girdle from the skull, the neck muscles themselves have a much earlier origin among the vertebrates. For example, lampreys possess hypobranchial muscles, and may also possess the cucullaris. Recent research in chick has established that these two muscles groups have different origins, the hypobranchial muscles having a somitic origin but the cucullaris muscle deriving from anterior lateral plate mesoderm associated with somites 1-3. Additionally, the cucullaris utilizes genetic pathways more similar to the head than the trunk musculature. Although the latter results are from experiments in the chick, cucullaris homologues occur in a variety of more basal vertebrates such as the sharks and zebrafish. Data are urgently needed from these taxa to determine whether the cucullaris in these groups also derives from lateral plate mesoderm or from the anterior somites, and whether the former or the latter represent the basal vertebrate condition. Other lateral plate mesoderm derivatives include the appendicular skeleton (fins, limbs and supporting girdles). If the cucullaris is a definitive lateral plate-derived structure it may have evolved in conjunction with the shoulder/limb skeleton in vertebrates and thereby provided a greater degree of flexibility to the heads of predatory vertebrates. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

  5. Regulatory heterochronies and loose temporal scaling between sea star and sea urchin regulatory circuits.

    Science.gov (United States)

    Gildor, Tsvia; Hinman, Veronica; Ben-Tabou-De-Leon, Smadar

    2017-01-01

    It has long been argued that heterochrony, a change in relative timing of a developmental process, is a major source of evolutionary innovation. Heterochronic changes of regulatory gene activation could be the underlying molecular mechanism driving heterochronic changes through evolution. Here, we compare the temporal expression profiles of key regulatory circuits between sea urchin and sea star, representative of two classes of Echinoderms that shared a common ancestor about 500 million years ago. The morphologies of the sea urchin and sea star embryos are largely comparable, yet, differences in certain mesodermal cell types and ectodermal patterning result in distinct larval body plans. We generated high resolution temporal profiles of 17 mesodermally-, endodermally- and ectodermally-expressed regulatory genes in the sea star, Patiria miniata, and compared these to their orthologs in the Mediterranean sea urchin, Paracentrotus lividus. We found that the maternal to zygotic transition is delayed in the sea star compared to the sea urchin, in agreement with the longer cleavage stage in the sea star. Interestingly, the order of gene activation shows the highest variation in the relatively diverged mesodermal circuit, while the correlations of expression dynamics are the highest in the strongly conserved endodermal circuit. We detected loose scaling of the developmental rates of these species and observed interspecies heterochronies within all studied regulatory circuits. Thus, after 500 million years of parallel evolution, mild heterochronies between the species are frequently observed and the tight temporal scaling observed for closely related species no longer holds.

  6. Analysis of coelom development in the sea urchin Holopneustes purpurescens yielding a deuterostome body plan

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    Valerie B. Morris

    2016-03-01

    Full Text Available An analysis of early coelom development in the echinoid Holopneustes purpurescens yields a deuterostome body plan that explains the disparity between the pentameral plan of echinoderms and the bilateral plans of chordates and hemichordates, the three major phyla of the monophyletic deuterostomes. The analysis shows an early separation into a medial hydrocoele and lateral coelomic mesoderm with an enteric channel between them before the hydrocoele forms the pentameral plan of five primary podia. The deuterostome body plan thus has a single axial or medial coelom and a pair of lateral coeloms, all surrounding an enteric channel, the gut channel. Applied to the phyla, the medial coelom is the hydrocoele in echinoderms, the notochord in chordates and the proboscis coelom in hemichordates: the lateral coeloms are the coelomic mesoderm in echinoderms, the paraxial mesoderm in chordates and the lateral coeloms in hemichordates. The plan fits frog and chick development and the echinoderm fossil record, and predicts genes involved in coelomogenesis as the source of deuterostome macroevolution.

  7. Endogenous WNT Signals Mediate BMP-Induced and Spontaneous Differentiation of Epiblast Stem Cells and Human Embryonic Stem Cells

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    Dorota Kurek

    2015-01-01

    Full Text Available Therapeutic application of human embryonic stem cells (hESCs requires precise control over their differentiation. However, spontaneous differentiation is prevalent, and growth factors induce multiple cell types; e.g., the mesoderm inducer BMP4 generates both mesoderm and trophoblast. Here we identify endogenous WNT signals as BMP targets that are required and sufficient for mesoderm induction, while trophoblast induction is WNT independent, enabling the exclusive differentiation toward either lineage. Furthermore, endogenous WNT signals induce loss of pluripotency in hESCs and their murine counterparts, epiblast stem cells (EpiSCs. WNT inhibition obviates the need to manually remove differentiated cells to maintain cultures and improves the efficiency of directed differentiation. In EpiSCs, WNT inhibition stabilizes a pregastrula epiblast state with novel characteristics, including the ability to contribute to blastocyst chimeras. Our findings show that endogenous WNT signals function as hidden mediators of growth factor-induced differentiation and play critical roles in the self-renewal of hESCs and EpiSCs.

  8. Embryogenesis of the Uropygial Glands in the Laysan Albatross (Phoebastria immutabilis (Rothschild, 1893): Procellariiformes).

    Science.gov (United States)

    Rehorek, S J; Wu, J L; Smith, T D; Beeching, S C

    2017-08-01

    An avian uropygial gland is located on the mid-dorsum of the tail, and is the only external gland found in birds. Most studies have focused on the function, gross anatomy and chemical nature of this gland, with little research on its ontogeny. The purpose of this study was to examine the development of this gland in a series of Laysan Albatross (Phoebastria immutabilis) embryos. Specimens were examined anatomically and histologically. It was found that grooves preceded glandular development by many stages. The embryogenesis of the uropygial gland was divided into 6 phases: preinception, groove inception, mesodermal separation, migrating mesodermal cells, oval shaped "depressions", constriction and finally glandular inception. No other gland is known to develop similarly, though there may be parallels with femoral gland development. In comparison to other bird species, the length of the development period in the Albatross, as well as other compounding factors, make it difficult to determine the significance of these observations. The development of a mesodermal band, soon to be a connective tissue capsule, is more complex than originally described in ducks. Thus, the unique nature of this gland is established, but the significance of the observations required further studies into uropygial gland development. Anat Rec, 300:1420-1428, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Divergent and conserved roles of Dll1 signaling in development of craniofacial and trunk muscle.

    Science.gov (United States)

    Czajkowski, Maciej T; Rassek, Claudia; Lenhard, Diana C; Bröhl, Dominique; Birchmeier, Carmen

    2014-11-15

    Craniofacial and trunk skeletal muscles are evolutionarily distinct and derive from cranial and somitic mesoderm, respectively. Different regulatory hierarchies act upstream of myogenic regulatory factors in cranial and somitic mesoderm, but the same core regulatory network - MyoD, Myf5 and Mrf4 - executes the myogenic differentiation program. Notch signaling controls self-renewal of myogenic progenitors as well as satellite cell homing during formation of trunk muscle, but its role in craniofacial muscles has been little investigated. We show here that the pool of myogenic progenitor cells in craniofacial muscle of Dll1(LacZ/Ki) mutant mice is depleted in early fetal development, which is accompanied by a major deficit in muscle growth. At the expense of progenitor cells, supernumerary differentiating myoblasts appear transiently and these express MyoD. The progenitor pool in craniofacial muscle of Dll1(LacZ/Ki) mutants is largely rescued by an additional mutation of MyoD. We conclude from this that Notch exerts its decisive role in craniofacial myogenesis by repression of MyoD. This function is similar to the one previously observed in trunk myogenesis, and is thus conserved in cranial and trunk muscle. However, in cranial mesoderm-derived progenitors, Notch signaling is not required for Pax7 expression and impinges little on the homing of satellite cells. Thus, Dll1 functions in satellite cell homing and Pax7 expression diverge in cranial- and somite-derived muscle. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Lhx1 is required for specification of the renal progenitor cell field.

    Directory of Open Access Journals (Sweden)

    M Cecilia Cirio

    2011-04-01

    Full Text Available In the vertebrate embryo, the kidney is derived from the intermediate mesoderm. The LIM-class homeobox transcription factor lhx1 is expressed early in the intermediate mesoderm and is one of the first genes to be expressed in the nephric mesenchyme. In this study, we investigated the role of Lhx1 in specification of the kidney field by either overexpressing or depleting lhx1 in Xenopus embryos or depleting lhx1 in an explant culture system. By overexpressing a constitutively-active form of Lhx1, we established its capacity to expand the kidney field during the specification stage of kidney organogenesis. In addition, the ability of Lhx1 to expand the kidney field diminishes as kidney organogenesis transitions to the morphogenesis stage. In a complimentary set of experiments, we determined that embryos depleted of lhx1, show an almost complete loss of the kidney field. Using an explant culture system to induce kidney tissue, we confirmed that expression of genes from both proximal and distal kidney structures is affected by the absence of lhx1. Taken together our results demonstrate an essential role for Lhx1 in driving specification of the entire kidney field from the intermediate mesoderm.

  11. Msx1 and Msx2 in limb mesenchyme modulate digit number and identity.

    Science.gov (United States)

    Bensoussan-Trigano, Vardina; Lallemand, Yvan; Saint Cloment, Cécile; Robert, Benoît

    2011-05-01

    Msx1 and Msx2 encode homeodomain transcription factors that play a crucial role in limb development. However, the limb phenotype of the double Msx1(null/null) Msx2(null/null) mutant is difficult to analyze, particularly along the anteroposterior axis, because of the complex effects of the double mutation on both ectoderm- and mesoderm-derived structures. Namely, in the mutant, formation of the apical ectodermal ridge (AER) is impaired anteriorly and, consequently, the subjacent mesenchyme does not form. Using the Cre/loxP system, we investigated the respective roles of Msx genes in ectoderm and mesoderm by generating conditional mutant embryos with no Msx activity solely in the mesoderm. In these mutants, the integrity of the ectoderm-derived AER was maintained, allowing formation of the anterior mesenchyme. With this strategy, we demonstrate that mesenchymal expression of Msx1 and Msx2 is required for proper Shh and Bmp4 signaling to specify digit number and identity. Copyright © 2011 Wiley-Liss, Inc.

  12. Molecular Mechanism of Somite Development

    Directory of Open Access Journals (Sweden)

    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

  13. Robustness and Accuracy in Sea Urchin Developmental Gene Regulatory Networks.

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    Ben-Tabou de-Leon, Smadar

    2016-01-01

    Developmental gene regulatory networks robustly control the timely activation of regulatory and differentiation genes. The structure of these networks underlies their capacity to buffer intrinsic and extrinsic noise and maintain embryonic morphology. Here I illustrate how the use of specific architectures by the sea urchin developmental regulatory networks enables the robust control of cell fate decisions. The Wnt-βcatenin signaling pathway patterns the primary embryonic axis while the BMP signaling pathway patterns the secondary embryonic axis in the sea urchin embryo and across bilateria. Interestingly, in the sea urchin in both cases, the signaling pathway that defines the axis controls directly the expression of a set of downstream regulatory genes. I propose that this direct activation of a set of regulatory genes enables a uniform regulatory response and a clear cut cell fate decision in the endoderm and in the dorsal ectoderm. The specification of the mesodermal pigment cell lineage is activated by Delta signaling that initiates a triple positive feedback loop that locks down the pigment specification state. I propose that the use of compound positive feedback circuitry provides the endodermal cells enough time to turn off mesodermal genes and ensures correct mesoderm vs. endoderm fate decision. Thus, I argue that understanding the control properties of repeatedly used regulatory architectures illuminates their role in embryogenesis and provides possible explanations to their resistance to evolutionary change.

  14. Robustness and accuracy in sea urchin developmental gene regulatory networks

    Directory of Open Access Journals (Sweden)

    Smadar eBen-Tabou De-Leon

    2016-02-01

    Full Text Available Developmental gene regulatory networks robustly control the timely activation of regulatory and differentiation genes. The structure of these networks underlies their capacity to buffer intrinsic and extrinsic noise and maintain embryonic morphology. Here I illustrate how the use of specific architectures by the sea urchin developmental regulatory networks enables the robust control of cell fate decisions. The Wnt-βcatenin signaling pathway patterns the primary embryonic axis while the BMP signaling pathway patterns the secondary embryonic axis in the sea urchin embryo and across bilateria. Interestingly, in the sea urchin in both cases, the signaling pathway that defines the axis controls directly the expression of a set of downstream regulatory genes. I propose that this direct activation of a set of regulatory genes enables a uniform regulatory response and a clear cut cell fate decision in the endoderm and in the dorsal ectoderm. The specification of the mesodermal pigment cell lineage is activated by Delta signaling that initiates a triple positive feedback loop that locks down the pigment specification state. I propose that the use of compound positive feedback circuitry provides the endodermal cells enough time to turn off mesodermal genes and ensures correct mesoderm vs. endoderm fate decision. Thus, I argue that understanding the control properties of repeatedly used regulatory architectures illuminates their role in embryogenesis and provides possible explanations to their resistance to evolutionary change.

  15. A sticky problem: the Xenopus cement gland as a paradigm for anteroposterior patterning.

    Science.gov (United States)

    Sive, H; Bradley, L

    1996-03-01

    The cement gland is a mucus-secreting organ found at the extreme anterior of frog embryos. It attaches the embryo to a solid support before swimming and feeding begin, and also serves a related sensory function that stops the embryo from moving once it is attached. Cement gland is an extremely useful anterior marker, whose study continues to yield fundamental information concerning vertebrate axial patterning. Cement gland arises from the outer layer of the embryonic ectoderm and, in Xenopus, forms a cone of columnar epithelium. It is the first ectodermal organ to differentiate, beginning to do so by late gastrula. A battery of genes expressed in the developing and mature cement gland serve as useful markers. Cement gland development can be influenced by both stimulatory and inhibitory cell interactions. Stimulatory signals arise from the anterior neural plate, head endoderm, and the dorsal mesoderm. Inhibitory signals are present in the posterior dorsal mesoderm and in ventral ectoderm and mesoderm. Further, signalling between the ectodermal layers may restrict cement gland differentiation to the outer ectodermal cells. Several secreted molecules are able to induce or repress cement gland formation: these include noggin, follistatin, hedgehog, chordin, retinoic acid, embryonic fibroblast growth factor (eFGF), Bone Morphogenetic Protein-4 (BMP-4), and Xwnt-8. Several of these factors alter expression of the homeodomain gene Xotx2, which may be a transcriptional activator of cement gland differentiation genes. The significance of the cell interactions and factors described in positioning cement gland at the front of the embryo is explored.

  16. Pitx2 is a critical early regulatory gene in normal cecal development.

    Science.gov (United States)

    Nichol, Peter F; Saijoh, Yukio

    2011-09-01

    The murine cecum is a critical digestive structure. Morphogenesis of the cecum involves several key genes, including Homeobox (Hox) d12. Ectopic expression of Hoxd12 has been shown to result in cecal agenesis and a down-regulation of both Fibroblast growth factor 10 (Fgf10) and the Pituitary homeobox 2 gene (Pitx2). Homozygous null mutation of Fgf10 or its cognate receptor Fgfr2IIIb results in severe cecal defects where there is the initiation of mesodermal budding, but a failure of the endoderm to grow and extend into this structure. We examined the expression of Pitx2 in the cecum and hypothesized that homozygous null mutation of Pitx2 would result in cecal agenesis. IACUC approval was obtained for these studies. Whole mount in situ hybridizations for Pitx2 were performed on wild-type embryos between embryonic d (E)11.0 and E12.5. Pitx2 -/- and Fgfr2IIIb -/- embryos were generated from n/+ heterozygote breedings and harvested at E10.5, E11.5, and E13.5. Genotypes were confirmed by PCR. Morphology of Pitx2 -/- cecae were compared with those of wild-type littermates and Fgfr2IIIb -/- embryos at identical stages. Embryos were fixed overnight and photographed the following day. Pitx2 is expressed in the cecal mesoderm and endoderm as early as E11.0. Expression becomes increasingly more robust by E12.5. Homozygous null mutation of Pitx2 results in agenesis of the cecum. In contrast to Fgfr2IIIb -/- embryos, which demonstrate a persistent mesodermal bud as late as E18.5, no mesodermal bud is present in Pitx2 -/- embryos. Our findings demonstrate that Pitx2 is a critical regulatory gene in cecal morphogenesis and suggest that Pitx2 is required for initiation of mesodermal budding and likely resides upstream of Fgf10-Fgfr2IIIb signaling in the normal development of this structure. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Stepwise renal lineage differentiation of mouse embryonic stem cells tracing in vivo development

    Energy Technology Data Exchange (ETDEWEB)

    Nishikawa, Masaki, E-mail: masakiwestriver@gmail.com [Medical and Research Services, Greater Los Angeles Veterans Affairs Healthcare System at Sepulveda, North Hills, CA (United States); University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 91343 (United States); Yanagawa, Naomi [Medical and Research Services, Greater Los Angeles Veterans Affairs Healthcare System at Sepulveda, North Hills, CA (United States); University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 91343 (United States); Kojima, Nobuhiko [Institute of Industrial Science (IIS), University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505 (Japan); Yuri, Shunsuke; Hauser, Peter V.; Jo, Oak D.; Yanagawa, Norimoto [Medical and Research Services, Greater Los Angeles Veterans Affairs Healthcare System at Sepulveda, North Hills, CA (United States); University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 91343 (United States)

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer We induced renal lineages from mESCs by following the in vivo developmental cues. Black-Right-Pointing-Pointer We induced nephrogenic intermediate mesoderm by stepwise addition of factors. Black-Right-Pointing-Pointer We induced two types of renal progenitor cells by reciprocal conditioned media. Black-Right-Pointing-Pointer We propose the potential role of CD24 for the enrichment of renal lineage cells. -- Abstract: The in vitro derivation of renal lineage progenitor cells is essential for renal cell therapy and regeneration. Despite extensive studies in the past, a protocol for renal lineage induction from embryonic stem cells remains unestablished. In this study, we aimed to induce renal lineages from mouse embryonic stem cells (mESC) by following in vivo developmental stages, i.e., the induction of mesoderm (Stage I), intermediate mesoderm (Stage II) and renal lineages (Stage III). For stage I induction, in accordance with known signaling pathways involved in mesoderm development in vivo, i.e., Nodal, bone morphogenic proteins (BMPs) and Wnt, we found that the sequential addition of three factors, i.e., Activin-A (A), a surrogate for Nodal signaling, during days 0-2, A plus BMP-4 (4) during days 2-4, and A4 plus lithium (L), a surrogate for Wnt signaling, during days 4-6, was most effective to induce the mesodermal marker, Brachyury. For stage II induction, the addition of retinoic acid (R) in the continuous presence of A4L during days 6-8 was most effective to induce nephrogenic intermediate mesodermal markers, such as Pax2 and Lim1. Under this condition, more than 30% of cells were stained positive for Pax2, and there was a concomitant decrease in the expression of non-mesodermal markers. For stage III induction, in resemblance to the reciprocal induction between ureteric bud (UB) and metanephric mesenchyme (MM) during kidney development, we found that the exposure to conditioned media derived from UB and MM cells was

  18. NFAT5 regulates the canonical Wnt pathway and is required for cardiomyogenic differentiation

    International Nuclear Information System (INIS)

    Adachi, Atsuo; Takahashi, Tomosaburo; Ogata, Takehiro; Imoto-Tsubakimoto, Hiroko; Nakanishi, Naohiko; Ueyama, Tomomi; Matsubara, Hiroaki

    2012-01-01

    Highlights: ► NFAT5 protein expression is downregulated during cardiomyogenesis. ► Inhibition of NFAT5 function suppresses canonical Wnt signaling. ► Inhibition of NFAT5 function attenuates mesodermal induction. ► NFAT5 function is required for cardiomyogenesis. -- Abstract: While nuclear factor of activated T cells 5 (NFAT5), a transcription factor implicated in osmotic stress response, is suggested to be involved in other processes such as migration and proliferation, its role in cardiomyogenesis is largely unknown. Here, we examined the role of NFAT5 in cardiac differentiation of P19CL6 cells, and observed that it was abundantly expressed in undifferentiated P19CL6 cells, and its protein expression was significantly downregulated by enhanced proteasomal degradation during DMSO-induced cardiomyogenesis. Expression of a dominant negative mutant of NFAT5 markedly attenuated cardiomyogenesis, which was associated with the inhibition of mesodermal differentiation. TOPflash reporter assay revealed that the transcriptional activity of canonical Wnt signaling was activated prior to mesodermal differentiation, and this activation was markedly attenuated by NFAT5 inhibition. Pharmacological activation of canonical Wnt signaling by [2′Z, 3′E]-6-bromoindirubin-3′-oxime (BIO) restored Brachyury expression in NFAT5DN-expressing cells. Inhibition of NFAT5 markedly attenuated Wnt3 and Wnt3a induction. Expression of Dkk1 and Cerberus1, which are secreted Wnt antagonists, was also inhibited by NFAT5 inhibition. Thus, endogenous NFAT5 regulates the coordinated expression of Wnt ligands and antagonists, which are essential for cardiomyogenesis through the canonical Wnt pathway. These results demonstrated a novel role of NFAT5 in cardiac differentiation of stem cells.

  19. Genome-wide screens for in vivo Tinman binding sites identify cardiac enhancers with diverse functional architectures.

    Directory of Open Access Journals (Sweden)

    Hong Jin

    Full Text Available The NK homeodomain factor Tinman is a crucial regulator of early mesoderm patterning and, together with the GATA factor Pannier and the Dorsocross T-box factors, serves as one of the key cardiogenic factors during specification and differentiation of heart cells. Although the basic framework of regulatory interactions driving heart development has been worked out, only about a dozen genes involved in heart development have been designated as direct Tinman target genes to date, and detailed information about the functional architectures of their cardiac enhancers is lacking. We have used immunoprecipitation of chromatin (ChIP from embryos at two different stages of early cardiogenesis to obtain a global overview of the sequences bound by Tinman in vivo and their linked genes. Our data from the analysis of ~50 sequences with high Tinman occupancy show that the majority of such sequences act as enhancers in various mesodermal tissues in which Tinman is active. All of the dorsal mesodermal and cardiac enhancers, but not some of the others, require tinman function. The cardiac enhancers feature diverse arrangements of binding motifs for Tinman, Pannier, and Dorsocross. By employing these cardiac and non-cardiac enhancers in machine learning approaches, we identify a novel motif, termed CEE, as a classifier for cardiac enhancers. In vivo assays for the requirement of the binding motifs of Tinman, Pannier, and Dorsocross, as well as the CEE motifs in a set of cardiac enhancers, show that the Tinman sites are essential in all but one of the tested enhancers; although on occasion they can be functionally redundant with Dorsocross sites. The enhancers differ widely with respect to their requirement for Pannier, Dorsocross, and CEE sites, which we ascribe to their different position in the regulatory circuitry, their distinct temporal and spatial activities during cardiogenesis, and functional redundancies among different factor binding sites.

  20. Small heat shock proteins are necessary for heart migration and laterality determination in zebrafish

    Science.gov (United States)

    Lahvic, Jamie L.; Ji, Yongchang; Marin, Paloma; Zuflacht, Jonah P.; Springel, Mark W.; Wosen, Jonathan E.; Davis, Leigh; Hutson, Lara D.; Amack, Jeffrey D.; Marvin, Martha J.

    2013-01-01

    Small heat shock proteins (sHsps) regulate cellular functions not only under stress, but also during normal development, when they are expressed in organ-specific patterns. Here we demonstrate that two small heat shock proteins expressed in embryonic zebrafish heart, hspb7 and hspb12, have roles in the development of left-right asymmetry. In zebrafish, laterality is determined by the motility of cilia in Kupffer’s vesicle (KV), where hspb7 is expressed; knockdown of hspb7 causes laterality defects by disrupting the motility of these cilia. In embryos with reduced hspb7, the axonemes of KV cilia have a 9+0 structure, while control embyros have a predominately 9+2 structure. Reduction of either hspb7 or hspb12 alters the expression pattern of genes that propagate the signals that establish left-right asymmetry: the nodal-related gene southpaw (spaw) in the lateral plate mesoderm, and its downstream targets pitx2, lefty1 and lefty2. Partial depletion of hspb7 causes concordant heart, brain and visceral laterality defects, indicating that loss of KV cilia motility leads causes coordinated but randomized laterality. Reducing hspb12 leads to similar alterations in the expression of downstream laterality genes, but at a lower penetrance. Simultaneous reduction of hspb7 and hspb12 randomizes heart, brain and visceral laterality, suggesting that these two genes have partially redundant functions in the establishment of left-right asymmetry. In addition, both hspb7 and hspb12 are expressed in the precardiac mesoderm and in the yolk syncytial layer, which supports the migration and fusion of mesodermal cardiac precursors. In embryos in which the reduction of hspb7 or hspb12 was limited to the yolk, migration defects predominated, suggesting that the yolk expression of these genes rather than heart expression is responsible for the migration defects. PMID:24140541

  1. Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications.

    Science.gov (United States)

    Coppola, Antonietta; Romito, Antonio; Borel, Christelle; Gehrig, Corinne; Gagnebin, Maryline; Falconnet, Emilie; Izzo, Antonella; Altucci, Lucia; Banfi, Sandro; Antonarakis, Stylianos E; Minchiotti, Gabriella; Cobellis, Gilda

    2014-03-01

    Understanding the molecular basis of cardiomyocyte development is critical for understanding the pathogenesis of pre- and post-natal cardiac disease. MicroRNAs (miRNAs) are post-transcriptional modulators of gene expression that play an important role in many developmental processes. Here, we show that the miR-99a/let-7c cluster, mapping on human chromosome 21, is involved in the control of cardiomyogenesis by altering epigenetic factors. By perturbing miRNA expression in mouse embryonic stem cells, we find that let-7c promotes cardiomyogenesis by upregulating genes involved in mesoderm specification (T/Bra and Nodal) and cardiac differentiation (Mesp1, Nkx2.5 and Tbx5). The action of let-7c is restricted to the early phase of mesoderm formation at the expense of endoderm and its late activation redirects cells toward other mesodermal derivatives. The Polycomb complex group protein Ezh2 is a direct target of let-7c, which promotes cardiac differentiation by modifying the H3K27me3 marks from the promoters of crucial cardiac transcription factors (Nkx2.5, Mef2c, Tbx5). In contrast, miR-99a represses cardiac differentiation via the nucleosome-remodeling factor Smarca5, attenuating the Nodal/Smad2 signaling. We demonstrated that the identified targets are underexpressed in human Down syndrome fetal heart specimens. By perturbing the expression levels of these miRNAs in embryonic stem cells, we were able to demonstrate that these miRNAs control lineage- and stage-specific transcription factors, working in concert with chromatin modifiers to direct cardiomyogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Human adipose tissue possesses a unique population of pluripotent stem cells with nontumorigenic and low telomerase activities: potential implications in regenerative medicine.

    Science.gov (United States)

    Ogura, Fumitaka; Wakao, Shohei; Kuroda, Yasumasa; Tsuchiyama, Kenichiro; Bagheri, Mozhdeh; Heneidi, Saleh; Chazenbalk, Gregorio; Aiba, Setsuya; Dezawa, Mari

    2014-04-01

    In this study, we demonstrate that a small population of pluripotent stem cells, termed adipose multilineage-differentiating stress-enduring (adipose-Muse) cells, exist in adult human adipose tissue and adipose-derived mesenchymal stem cells (adipose-MSCs). They can be identified as cells positive for both MSC markers (CD105 and CD90) and human pluripotent stem cell marker SSEA-3. They intrinsically retain lineage plasticity and the ability to self-renew. They spontaneously generate cells representative of all three germ layers from a single cell and successfully differentiate into targeted cells by cytokine induction. Cells other than adipose-Muse cells exist in adipose-MSCs, however, do not exhibit these properties and are unable to cross the boundaries from mesodermal to ectodermal or endodermal lineages even under cytokine inductions. Importantly, adipose-Muse cells demonstrate low telomerase activity and transplants do not promote teratogenesis in vivo. When compared with bone marrow (BM)- and dermal-Muse cells, adipose-Muse cells have the tendency to exhibit higher expression in mesodermal lineage markers, while BM- and dermal-Muse cells were generally higher in those of ectodermal and endodermal lineages. Adipose-Muse cells distinguish themselves as both easily obtainable and versatile in their capacity for differentiation, while low telomerase activity and lack of teratoma formation make these cells a practical cell source for potential stem cell therapies. Further, they will promote the effectiveness of currently performed adipose-MSC transplantation, particularly for ectodermal and endodermal tissues where transplanted cells need to differentiate across the lineage from mesodermal to ectodermal or endodermal in order to replenish lost cells for tissue repair.

  3. The Notch Ligand Delta-Like 4 Regulates Multiple Stages of Early Hemato-Vascular Development

    Science.gov (United States)

    Neves, Hélia; Gomes, Andreia C.; Saavedra, Pedro; Carvalho, Catarina C.; Duarte, António; Cidadão, António; Parreira, Leonor

    2012-01-01

    Background In mouse embryos, homozygous or heterozygous deletions of the gene encoding the Notch ligand Dll4 result in early embryonic death due to major defects in endothelial remodeling in the yolk sac and embryo. Considering the close developmental relationship between endothelial and hematopoietic cell lineages, which share a common mesoderm-derived precursor, the hemangioblast, and many key regulatory molecules, we investigated whether Dll4 is also involved in the regulation of early embryonic hematopoiesis. Methodology/Principal Findings Using Embryoid Bodies (EBs) derived from embryonic stem cells harboring hetero- or homozygous Dll4 deletions, we observed that EBs from both genotypes exhibit an abnormal endothelial remodeling in the vascular sprouts that arise late during EB differentiation, indicating that this in vitro system recapitulates the angiogenic phenotype of Dll4 mutant embryos. However, analysis of EB development at early time points revealed that the absence of Dll4 delays the emergence of mesoderm and severely reduces the number of blast-colony forming cells (BL-CFCs), the in vitro counterpart of the hemangioblast, and of endothelial cells. Analysis of colony forming units (CFU) in EBs and yolk sacs from Dll4+/− and Dll4−/− embryos, showed that primitive erythropoiesis is specifically affected by Dll4 insufficiency. In Dll4 mutant EBs, smooth muscle cells (SMCs) were seemingly unaffected and cardiomyocyte differentiation was increased, indicating that SMC specification is Dll4-independent while a normal dose of this Notch ligand is essential for the quantitative regulation of cardiomyogenesis. Conclusions/Significance This study highlights a previously unnoticed role for Dll4 in the quantitative regulation of early hemato-vascular precursors, further indicating that it is also involved on the timely emergence of mesoderm in early embryogenesis. PMID:22514637

  4. Role of mesenchymal stem cells in osteoarthritis treatment

    Directory of Open Access Journals (Sweden)

    Ling Kong

    2017-04-01

    Full Text Available As the most common form of joint disorder, osteoarthritis (OA imposes a tremendous burden on health care systems worldwide. Without effective cure, OA represents a unique opportunity for innovation in therapeutic development. In contrast to traditional treatments based on drugs, proteins, or antibodies, stem cells are poised to revolutionize medicine as they possess the capacity to replace and repair tissues and organs such as osteoarthritic joints. Among different types of stem cells, mesenchymal stem cells (MSCs are of mesoderm origin and have been shown to generate cells for tissues of the mesoderm lineage, thus, raising the hope for them being used to treat diseases such as OA. However, given their ability to differentiate into other cell types, MSCs have also been tested in treating a myriad of conditions from diabetes to Parkinson's disease, apparently of the ectoderm and endoderm lineages. There are ongoing debates whether MSCs can differentiate into lineages outside of the mesoderm and consequently their effectiveness in treating conditions from the ectoderm and endoderm lineages. In this review, we discuss the developmental origin of MSCs, their differentiation potential and immunomodulatory effects, as well as their applications in treating OA. We suggest further investigations into new therapies or combination therapies that may provide more effective treatment for bone and joint diseases. Furthermore, cell-based therapy and its associated safety and effectiveness should be carefully evaluated before clinical translation. This review provides updated information on recent approval of clinical trials and related applications of MSCs, and discusses additional efforts on cell-based therapy for treating OA and other joint and bone diseases.

  5. Evolutionarily conserved morphogenetic movements at the vertebrate head-trunk interface coordinate the transport and assembly of hypopharyngeal structures.

    Science.gov (United States)

    Lours-Calet, Corinne; Alvares, Lucia E; El-Hanfy, Amira S; Gandesha, Saniel; Walters, Esther H; Sobreira, Débora Rodrigues; Wotton, Karl R; Jorge, Erika C; Lawson, Jennifer A; Kelsey Lewis, A; Tada, Masazumi; Sharpe, Colin; Kardon, Gabrielle; Dietrich, Susanne

    2014-06-15

    The vertebrate head-trunk interface (occipital region) has been heavily remodelled during evolution, and its development is still poorly understood. In extant jawed vertebrates, this region provides muscle precursors for the throat and tongue (hypopharyngeal/hypobranchial/hypoglossal muscle precursors, HMP) that take a stereotype path rostrally along the pharynx and are thought to reach their target sites via active migration. Yet, this projection pattern emerged in jawless vertebrates before the evolution of migratory muscle precursors. This suggests that a so far elusive, more basic transport mechanism must have existed and may still be traceable today. Here we show for the first time that all occipital tissues participate in well-conserved cell movements. These cell movements are spearheaded by the occipital lateral mesoderm and ectoderm that split into two streams. The rostrally directed stream projects along the floor of the pharynx and reaches as far rostrally as the floor of the mandibular arch and outflow tract of the heart. Notably, this stream leads and engulfs the later emerging HMP, neural crest cells and hypoglossal nerve. When we (i) attempted to redirect hypobranchial/hypoglossal muscle precursors towards various attractants, (ii) placed non-migratory muscle precursors into the occipital environment or (iii) molecularly or (iv) genetically rendered muscle precursors non-migratory, they still followed the trajectory set by the occipital lateral mesoderm and ectoderm. Thus, we have discovered evolutionarily conserved morphogenetic movements, driven by the occipital lateral mesoderm and ectoderm, that ensure cell transport and organ assembly at the head-trunk interface. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Maternal inheritance of twist and analysis of MAPK activation in embryos of the polychaete annelid Platynereis dumerilii.

    Directory of Open Access Journals (Sweden)

    Kathrin Pfeifer

    Full Text Available In this study, we aimed to identify molecular mechanisms involved in the specification of the 4d (mesentoblast lineage in Platynereis dumerilii. We employ RT-PCR and in situ hybridization against the Platynereis dumerilii twist homolog (Pdu-twist to reveal mesodermal specification within this lineage. We show that Pdu-twist mRNA is already maternally distributed. After fertilization, ooplasmatic segregation leads to relocation of Pdu-twist transcripts into the somatoblast (2d lineage and 4d, indicating that the maternal component of Pdu-twist might be an important prerequisite for further mesoderm specification but does not represent a defining characteristic of the mesentoblast. However, after the primordial germ cells have separated from the 4d lineage, zygotic transcription of Pdu-twist is exclusively observed in the myogenic progenitors, suggesting that mesodermal specification occurs after the 4d stage. Previous studies on spiral cleaving embryos revealed a spatio-temporal correlation between the 4d lineage and the activity of an embryonic organizer that is capable to induce the developmental fates of certain micromeres. This has raised the question if specification of the 4d lineage could be connected to the organizer activity. Therefore, we aimed to reveal the existence of such a proposed conserved organizer in Platynereis employing antibody staining against dpERK. In contrast to former observations in other spiralian embryos, activation of MAPK signaling during 2d and 4d formation cannot be detected which questions the existence of a conserved connection between organizer function and specification of the 4d lineage. However, our experiments unveil robust MAPK activation in the prospective nephroblasts as well as in the macromeres and some micromeres at the blastopore in gastrulating embryos. Inhibition of MAPK activation leads to larvae with a shortened body axis, defects in trunk muscle spreading and improper nervous system

  7. Lineage tracing of neuromesodermal progenitors reveals novel Wnt-dependent roles in trunk progenitor cell maintenance and differentiation.

    Science.gov (United States)

    Garriock, Robert J; Chalamalasetty, Ravindra B; Kennedy, Mark W; Canizales, Lauren C; Lewandoski, Mark; Yamaguchi, Terry P

    2015-05-01

    In the development of the vertebrate body plan, Wnt3a is thought to promote the formation of paraxial mesodermal progenitors (PMPs) of the trunk region while suppressing neural specification. Recent lineage-tracing experiments have demonstrated that these trunk neural progenitors and PMPs derive from a common multipotent progenitor called the neuromesodermal progenitor (NMP). NMPs are known to reside in the anterior primitive streak (PS) region; however, the extent to which NMPs populate the PS and contribute to the vertebrate body plan, and the precise role that Wnt3a plays in regulating NMP self-renewal and differentiation are unclear. To address this, we used cell-specific markers (Sox2 and T) and tamoxifen-induced Cre recombinase-based lineage tracing to locate putative NMPs in vivo. We provide functional evidence for NMP location primarily in the epithelial PS, and to a lesser degree in the ingressed PS. Lineage-tracing studies in Wnt3a/β-catenin signaling pathway mutants provide genetic evidence that trunk progenitors normally fated to enter the mesodermal germ layer can be redirected towards the neural lineage. These data, combined with previous PS lineage-tracing studies, support a model that epithelial anterior PS cells are Sox2(+)T(+) multipotent NMPs and form the bulk of neural progenitors and PMPs of the posterior trunk region. Finally, we find that Wnt3a/β-catenin signaling directs trunk progenitors towards PMP fates; however, our data also suggest that Wnt3a positively supports a progenitor state for both mesodermal and neural progenitors. © 2015. Published by The Company of Biologists Ltd.

  8. PTEN is involved in modulation of vasculogenesis in early chick embryos

    Science.gov (United States)

    Li, Yan; Wang, Xiao-yu; Wu, Ting; Chuai, Manli; Lee, Kenneth Ka Ho; Wang, Li-jing; Yang, Xuesong

    2013-01-01

    Summary PTEN is a tumor suppressor gene that is mutated and/or deleted in many types of tumor. This gene also plays a very distinct role in the early stages of embryonic development such as cell migration, proliferation and migration. Nevertheless, little is known of the function of PTEN in vasculogenesis during chick embryonic development. In this study, we used in situ hybridization to first demonstrate the expression pattern of PTEN during gastrulation. PTEN was found mainly expressed in the blood islands of area opaca, the neural tube and mesodermal structures. Overexpression of PTEN obstructed the epithelial–mesenchymal transition (EMT) process in the primitive streak. EMT is the first prerequisite required for the emigration of hemangioblasts during vasculogenesis. When PTEN expression was silenced, we observed that it produced an adverse effect on mesodermal cell emigration to the extra-embryonic blood islands. In addition, we also demonstrated that even if the perturbed-PTEN cells did not affect the formation of blood islands, migrant mesodermal cells overexpressing wt PTEN-GFP had difficulties integrating into the blood islands. Instead, these cells were either localized on the periphery of the blood islands or induced to differentiate into endothelial cells if they managed to integrate into blood islands. Development of the intra-embryonic primary vascular plexus was also affected by overexpression of PTEN. We proposed that it was elevated PTEN lipid phosphatase activity that was responsible for the morphogenetic defects induced by PTEN overexpression. In this context, we did not find PTEN affecting VEGF signaling. In sum, our study has provided evidence that PTEN is involved in vasculogenesis during the early stages of chick embryo development. PMID:23789109

  9. Cell lineage of timed cohorts of Tbx6-expressing cells in wild-type and Tbx6 mutant embryos.

    Science.gov (United States)

    Concepcion, Daniel; Washkowitz, Andrew J; DeSantis, Akiko; Ogea, Phillip; Yang, Jason I; Douglas, Nataki C; Papaioannou, Virginia E

    2017-07-15

    Tbx6 is a T-box transcription factor with multiple roles in embryonic development as evidenced by dramatic effects on mesoderm cell fate determination, left/right axis determination, and somite segmentation in mutant mice. The expression of Tbx6 is restricted to the primitive streak and presomitic mesoderm, but some of the phenotypic features of mutants are not easily explained by this expression pattern. We have used genetically-inducible fate mapping to trace the fate of Tbx6 -expressing cells in wild-type and mutant embryos to explain some of the puzzling features of the mutant phenotype. We created an inducible Tbx6-creERT2 transgenic mouse in which cre expression closely recapitulates endogenous Tbx6 expression both temporally and spatially. Using a lacZ-based Cre reporter and timed tamoxifen injections, we followed temporally overlapping cohorts of cells that had expressed Tbx6 and found contributions to virtually all mesodermally-derived embryonic structures as well as the extraembryonic allantois. Contribution to the endothelium of major blood vessels may account for the embryonic death of homozygous mutant embryos. In mutant embryos, Tbx6-creERT2-traced cells contributed to the abnormally segmented anterior somites and formed the characteristic ectopic neural tubes. Retention of cells in the mutant tail bud indicates a deficiency in migratory behavior of the mutant cells and the presence of Tbx6-creERT2-traced cells in the notochord, a node derivative provides a possible explanation for the heterotaxia seen in mutant embryos. © 2017. Published by The Company of Biologists Ltd.

  10. The hedgehog pathway gene shifted functions together with the hmgcr-dependent isoprenoid biosynthetic pathway to orchestrate germ cell migration.

    Directory of Open Access Journals (Sweden)

    Girish Deshpande

    Full Text Available The Drosophila embryonic gonad is assembled from two distinct cell types, the Primordial Germ Cells (PGCs and the Somatic Gonadal Precursor cells (SGPs. The PGCs form at the posterior of blastoderm stage embryos and are subsequently carried inside the embryo during gastrulation. To reach the SGPs, the PGCs must traverse the midgut wall and then migrate through the mesoderm. A combination of local repulsive cues and attractive signals emanating from the SGPs guide migration. We have investigated the role of the hedgehog (hh pathway gene shifted (shf in directing PGC migration. shf encodes a secreted protein that facilitates the long distance transmission of Hh through the proteoglycan matrix after it is released from basolateral membranes of Hh expressing cells in the wing imaginal disc. shf is expressed in the gonadal mesoderm, and loss- and gain-of-function experiments demonstrate that it is required for PGC migration. Previous studies have established that the hmgcr-dependent isoprenoid biosynthetic pathway plays a pivotal role in generating the PGC attractant both by the SGPs and by other tissues when hmgcr is ectopically expressed. We show that production of this PGC attractant depends upon shf as well as a second hh pathway gene gγ1. Further linking the PGC attractant to Hh, we present evidence indicating that ectopic expression of hmgcr in the nervous system promotes the release/transmission of the Hh ligand from these cells into and through the underlying mesodermal cell layer, where Hh can contact migrating PGCs. Finally, potentiation of Hh by hmgcr appears to depend upon cholesterol modification.

  11. Cell lineage of timed cohorts of Tbx6-expressing cells in wild-type and Tbx6 mutant embryos

    Directory of Open Access Journals (Sweden)

    Daniel Concepcion

    2017-07-01

    Full Text Available Tbx6 is a T-box transcription factor with multiple roles in embryonic development as evidenced by dramatic effects on mesoderm cell fate determination, left/right axis determination, and somite segmentation in mutant mice. The expression of Tbx6 is restricted to the primitive streak and presomitic mesoderm, but some of the phenotypic features of mutants are not easily explained by this expression pattern. We have used genetically-inducible fate mapping to trace the fate of Tbx6-expressing cells in wild-type and mutant embryos to explain some of the puzzling features of the mutant phenotype. We created an inducible Tbx6-creERT2 transgenic mouse in which cre expression closely recapitulates endogenous Tbx6 expression both temporally and spatially. Using a lacZ-based Cre reporter and timed tamoxifen injections, we followed temporally overlapping cohorts of cells that had expressed Tbx6 and found contributions to virtually all mesodermally-derived embryonic structures as well as the extraembryonic allantois. Contribution to the endothelium of major blood vessels may account for the embryonic death of homozygous mutant embryos. In mutant embryos, Tbx6-creERT2-traced cells contributed to the abnormally segmented anterior somites and formed the characteristic ectopic neural tubes. Retention of cells in the mutant tail bud indicates a deficiency in migratory behavior of the mutant cells and the presence of Tbx6-creERT2-traced cells in the notochord, a node derivative provides a possible explanation for the heterotaxia seen in mutant embryos.

  12. Expression of the pair-rule gene homologs runt, Pax3/7, even-skipped-1 and even-skipped-2 during larval and juvenile development of the polychaete annelid Capitella teleta does not support a role in segmentation

    Directory of Open Access Journals (Sweden)

    Seaver Elaine C

    2012-04-01

    Full Text Available Abstract Background Annelids and arthropods each possess a segmented body. Whether this similarity represents an evolutionary convergence or inheritance from a common segmented ancestor is the subject of ongoing investigation. Methods To investigate whether annelids and arthropods share molecular components that control segmentation, we isolated orthologs of the Drosophila melanogaster pair-rule genes, runt, paired (Pax3/7 and eve, from the polychaete annelid Capitella teleta and used whole mount in situ hybridization to characterize their expression patterns. Results When segments first appear, expression of the single C. teleta runt ortholog is only detected in the brain. Later, Ct-runt is expressed in the ventral nerve cord, foregut and hindgut. Analysis of Pax genes in the C. teleta genome reveals the presence of a single Pax3/7 ortholog. Ct-Pax3/7 is initially detected in the mid-body prior to segmentation, but is restricted to two longitudinal bands in the ventral ectoderm. Each of the two C. teleta eve orthologs has a unique and complex expression pattern, although there is partial overlap in several tissues. Prior to and during segment formation, Ct-eve1 and Ct-eve2 are both expressed in the bilaterial pair of mesoteloblasts, while Ct-eve1 is expressed in the descendant mesodermal band cells. At later stages, Ct-eve2 is expressed in the central and peripheral nervous system, and in mesoderm along the dorsal midline. In late stage larvae and adults, Ct-eve1 and Ct-eve2 are expressed in the posterior growth zone. Conclusions C. teleta eve, Pax3/7 and runt homologs all have distinct expression patterns and share expression domains with homologs from other bilaterians. None of the pair-rule orthologs examined in C. teleta exhibit segmental or pair-rule stripes of expression in the ectoderm or mesoderm, consistent with an independent origin of segmentation between annelids and arthropods.

  13. Embryonic and foetal Islet-1 positive cells in human hearts are also positive to c-Kit

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    C. Serradifalco

    2011-12-01

    Full Text Available During embryogenesis, the mammalian heart develops from a primitive heart tube originating from two bilateral primary heart fields located in the lateral plate mesoderm. Cells belongings to the pre-cardiac mesoderm will differentiate into early cardiac progenitors, which express early transcription factors which are also common to the Isl-1 positive cardiac progenitor cells isolated from the developing pharyngeal mesoderm and the foetal and post-natal mice hearts. A second population of cardiac progenitor cells positive to c-Kit has been abundantly isolated from adult hearts. Until now, these two populations have been considered two different sets of progenitor cells present in the heart in different stages of an individual life. In the present study we collected embryonic, foetal and infant hearts, and we tested the hypotheses that c-Kit positive cells, usually isolated from the adult heart, are also present in the intra-uterine life and persist in the adult heart after birth, and that foetal Isl-1 positive cells are also positive to c-Kit. Using immunohistochemistry we studied the temporal distribution of Isl-1 positive and c-Kit/CD105 double positive cells, and by immunofluorescence and confocal analysis we studied the co-localization of c-Kit and Isl-1 positive cells. The results indicated that cardiomyocytes and interstitial cells were positive for c-Kit from the 9th to the 19th gestational week, that cells positive for both c-Kit and CD105 appeared in the interstitium at the 17th gestational week and persisted in the postnatal age, and that the Isl-1 positive cells were a subset of the c-Kit positive population.

  14. Increased cardiogenesis in P19-GFP teratocarcinoma cells expressing the propeptide IGF-1Ea

    International Nuclear Information System (INIS)

    Poudel, Bhawana; Bilbao, Daniel; Sarathchandra, Padmini; Germack, Renee; Rosenthal, Nadia; Santini, Maria Paola

    2011-01-01

    Highlights: ► In this study, we explored the function of IGF-1Ea propeptide in inducing cardiogenesis of stem cells. ► IGF-1Ea promoted cardiac mesodermal induction in uncommitted cells. ► Under differentiation condition, IGF-1Ea increased expression of cardiac differentiation markers. ► Furthermore, it promoted formation of finely organized sarcomeric structure. ► IGF-1Ea propeptide may be a good candidate to improve production of cardiomyocytes from pluripotent cells. -- Abstract: The mechanism implicated in differentiation of endogenous cardiac stem cells into cardiomyocytes to regenerate the heart tissue upon an insult remains elusive, limiting the therapeutical goals to exogenous cell injection and/or gene therapy. We have shown previously that cardiac specific overexpression of the insulin-like growth factor 1 propeptide IGF-1Ea induces beneficial myocardial repair after infarct. Although the mechanism is still under investigation, the possibility that this propeptide may be involved in promoting stem cell differentiation into the cardiac lineage has yet to be explored. To investigate whether IGF-1Ea promote cardiogenesis, we initially modified P19 embryonal carcinoma cells to express IGF-1Ea. Taking advantage of their cardiomyogenic nature, we analyzed whether overexpression of this propeptide affected cardiac differentiation program. The data herein presented showed for the first time that constitutively overexpressed IGF-1Ea increased cardiogenic differentiation program in both undifferentiated and DMSO-differentiated cells. In details, IGF-1Ea overexpression promoted localization of alpha-actinin in finely organized sarcomeric structure compared to control cells and upregulated the cardiac mesodermal marker NKX-2.5 and the ventricular structural protein MLC2v. Furthermore, activated IGF-1 signaling promoted cardiac mesodermal induction in undifferentiated cells independently of cell proliferation. This analysis suggests that IGF-1Ea may be a

  15. Evolutionarily conserved morphogenetic movements at the vertebrate head–trunk interface coordinate the transport and assembly of hypopharyngeal structures

    Science.gov (United States)

    Lours-Calet, Corinne; Alvares, Lucia E.; El-Hanfy, Amira S.; Gandesha, Saniel; Walters, Esther H.; Sobreira, Débora Rodrigues; Wotton, Karl R.; Jorge, Erika C.; Lawson, Jennifer A.; Kelsey Lewis, A.; Tada, Masazumi; Sharpe, Colin; Kardon, Gabrielle; Dietrich, Susanne

    2014-01-01

    The vertebrate head–trunk interface (occipital region) has been heavily remodelled during evolution, and its development is still poorly understood. In extant jawed vertebrates, this region provides muscle precursors for the throat and tongue (hypopharyngeal/hypobranchial/hypoglossal muscle precursors, HMP) that take a stereotype path rostrally along the pharynx and are thought to reach their target sites via active migration. Yet, this projection pattern emerged in jawless vertebrates before the evolution of migratory muscle precursors. This suggests that a so far elusive, more basic transport mechanism must have existed and may still be traceable today. Here we show for the first time that all occipital tissues participate in well-conserved cell movements. These cell movements are spearheaded by the occipital lateral mesoderm and ectoderm that split into two streams. The rostrally directed stream projects along the floor of the pharynx and reaches as far rostrally as the floor of the mandibular arch and outflow tract of the heart. Notably, this stream leads and engulfs the later emerging HMP, neural crest cells and hypoglossal nerve. When we (i) attempted to redirect hypobranchial/hypoglossal muscle precursors towards various attractants, (ii) placed non-migratory muscle precursors into the occipital environment or (iii) molecularly or (iv) genetically rendered muscle precursors non-migratory, they still followed the trajectory set by the occipital lateral mesoderm and ectoderm. Thus, we have discovered evolutionarily conserved morphogenetic movements, driven by the occipital lateral mesoderm and ectoderm, that ensure cell transport and organ assembly at the head–trunk interface. PMID:24662046

  16. Immunogold-labeled S-phase neoblasts, total neoblast number, their distribution, and evidence for arrested neoblasts in Macrostomum lignano (Platyhelminthes, Rhabditophora).

    Science.gov (United States)

    Bode, A; Salvenmoser, W; Nimeth, K; Mahlknecht, M; Adamski, Z; Rieger, R M; Peter, R; Ladurner, P

    2006-09-01

    Neoblasts in Platyhelminthes are the only cells to proliferate and differentiate into all cell types. In Macrostomum lignano, the incorporation of 5'-bromo-2'-deoxyuridine (BrdU) in neoblasts confirmed the distribution of S-phase cells in two lateral bands. BrdU labeling for light and for transmission electron microscopy (TEM) identified three populations of proliferating cells: somatic neoblasts located between the epidermis and gastrodermis (mesodermal neoblasts), neoblasts located within the gastrodermis (gastrodermal neoblasts), and gonadal S-phase cells. In adults, three stages of mesodermal neoblasts (2, 2-3, and 3) defined by their ultrastructure were found. Stage 1 neoblasts where only seen in hatchlings. These stages either were phases within the S-phase of one neoblast pool or were subsequent stages of differentiating neoblasts, each with its own cell cycle. Regular TEM and immunogold labeling provided the basis for calculating the total number of neoblasts and the ratio of labeled to non-labeled neoblasts. Somatic neoblasts represented 6.5% of the total number of cells. Of these, 27% were labeled in S-phase. Of this fraction, 33% were in stage 2, 46% in stage 2-3, and 21% in stage 3. Immunogold labeling substantiated results concerning the differentiation of neoblasts into somatic cells. Non-labeled stage 2 neoblasts were present, even after a 2-week BrdU exposure. Double labeling of mitoses and FMRF-amide revealed a close spatial relationship of mesodermal neoblasts with the nervous system. Immunogold-labeled sections showed that nearly 70% of S-phase cells were in direct contact or within 5 microm from nerve cords.

  17. Ectopia lentis et pupillae

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    Gupta Naresh

    1989-01-01

    Full Text Available A rare case of congenital bilateral ectopia lentis et pupillae (ELEP is reported in a 32 year old female presenting with complaints of diminution of vision in both eyes. Associations of optic nerve hypoplasia and myelinated nerve fibers are being reported for the first time in such a case. The aetiopathogenesis of ELEP is controversial. Combined neuroectodermal and mesodermal origin is being postulated for this syndrome on the basis of aforesaid abnormalities and presence of pupillary dilator muscle hypoplasia, "annular endotheliopathy", and persistent pupillary membrane in both eyes.

  18. Immunohistochemical markers for corneal stem cells in the early developing human eye

    DEFF Research Database (Denmark)

    Lyngholm, Mikkel; Høyer, Poul E; Vorum, Henrik

    2008-01-01

    markers and potential markers for LSCs and early transient amplifying cells in human adults. In this study, we describe the development of the ectodermally derived LSCs and the mesodermally derived niche cells from the time at which the cornea is defined (week 6) until the formation of the early limbal...... niche (week 14) in human embryos and fetuses. The expression of SOD2 and CK15 was investigated together with other recently identified limbal proteins. Previously suggested LSC and differentiation markers (PAX6, aquaporin-1 and nestin) were also investigated. Both SOD2 and CK15 were present...

  19. Roentgenographic features of neurofibromatosis von Recklinghausen

    Energy Technology Data Exchange (ETDEWEB)

    Galanski, M.; Vogelsang, H.; Cramer, B.M.; Thun, F.; Peters, P.E.

    1983-10-01

    The basic abnormality of neurofibromatosis consists not only of a maldevelopment of the neuroectoderm but also of the mesoderm. Therefore any organ or system of the body may be involved. Following a short clinical review of the central (acoustic) and peripheral type the well known and the more unusual radiographic findings are summarized. They include cranial and intracranial manifestations (orbitosphenoid dysplasia, bone defects of the skull, acoustic neuroma, glioma of the optic nerve and chiasm, meningioma), spinal lesions (scoliosis, vetebral scalloping, meningocele, neuroma, ependymoma), skeletal abnormalities (pseudarthrosis), cardiovascular manifestations, pulmonary fibrosis, tumors of the gastrointestinal and urinary tract and different endocrinopathies. Some of the roentgeologic symptoms are very characteristic and allow definitive diagnosis.

  20. Prune belly syndrome with pouch colon and absent dermatome.

    Science.gov (United States)

    Baba, Aejaz A; Hussain, Syed A; Shera, Altaf H; Patnaik, Rekha

    2010-01-01

    Prune belly syndrome (PBS) is a rare congenital constellation of defects in pediatric surgical practice. Although anorectal anomalies have been reported in association with PBS, only few case of pouch colon with PBS has been reported. [1] In addition, our patient had deficient abdominal wall with absent dermatome in left upper quadrant, which has never been reported in the English literature. This association with abdominal wall deficiency and absent dermatome not only strengthens the theory of mesodermal arrest in the etiology of PBS but also points towards a defect in the ectodermal development.

  1. Prune belly syndrome with pouch colon and absent dermatome

    Directory of Open Access Journals (Sweden)

    Baba Aejaz

    2010-01-01

    Full Text Available Prune belly syndrome (PBS is a rare congenital constellation of defects in pediatric surgical practice. Although anorectal anomalies have been reported in association with PBS, only few case of pouch colon with PBS has been reported. [1] In addition, our patient had deficient abdominal wall with absent dermatome in left upper quadrant, which has never been reported in the English literature. This association with abdominal wall deficiency and absent dermatome not only strengthens the theory of mesodermal arrest in the etiology of PBS but also points towards a defect in the ectodermal development.

  2. L’ectoderme, le mésoderme et le neurectoderme sont des types tissulaires importants pour la compréhension et la prévention des résorptions radiculaires. Recommandations cliniques

    DEFF Research Database (Denmark)

    Kjær, Inger

    2016-01-01

    for root resorption (ectoderm and mesoderm), so are local or general virus attacks (neuroectoderm). Resorption often occurs in dentitions never treated orthodontically. MATERIAL AND METHOD: The author performed a review of the literature in order to present a new diagnostic approach incorporating...... histological and embryological concepts. RESULTS: The review revealed different etiologies and sites involved in root resorption. Patients presenting variations of the peri-root sheet are most exposed to root resorption. DISCUSSION: At this stage, it is difficult to diagnose these variations. The author offers...

  3. EphrinB1/EphB3b Coordinate Bidirectional Epithelial-Mesenchymal Interactions Controlling Liver Morphogenesis and Laterality

    DEFF Research Database (Denmark)

    Cayuso, Jordi; Dzementsei, Aliaksandr; Fischer, Johanna C

    2016-01-01

    Positioning organs in the body often requires the movement of multiple tissues, yet the molecular and cellular mechanisms coordinating such movements are largely unknown. Here, we show that bidirectional signaling between EphrinB1 and EphB3b coordinates the movements of the hepatic endoderm...... and adjacent lateral plate mesoderm (LPM), resulting in asymmetric positioning of the zebrafish liver. EphrinB1 in hepatoblasts regulates directional migration and mediates interactions with the LPM, where EphB3b controls polarity and movement of the LPM. EphB3b in the LPM concomitantly repels hepatoblasts...

  4. An interview with Jim Smith.

    Science.gov (United States)

    Maartens, Aidan

    2017-08-01

    Jim Smith is Director of Science at the Wellcome Trust and a group leader at the Francis Crick Institute, where he was formerly Director of Research. A Fellow of both the Royal Society and the Academy of Medical Sciences, he was knighted for his services to medical research and science education in 2016. His lab works on mesoderm induction in the early vertebrate embryo. We met Jim in the Crick to hear about his life in science, his visions for the Crick and the Wellcome Trust, and his advice for early career scientists. © 2017. Published by The Company of Biologists Ltd.

  5. Three-dimensional localisation of NANOG, OCT4, and E-CADHERIN in porcine pre- and peri-implantation embryos

    DEFF Research Database (Denmark)

    Wolf, Xenia Asbæk; Serup, Palle; Hyttel, Poul

    2011-01-01

    The expression patterns of NANOG and OCT4 have previously been reported to differ markedly between mammalian species indicating distinct species-specific roles during development. We investigate the three-dimensional expression pattern of NANOG and OCT4 in porcine pre- and peri-implantation embryos...... NANOG was localised to nuclei in a minor portion of the epiblast cells in which E-CADHERIN seemed to be up-regulated and OCT4 down-regulated. Later NANOG was restricted to the potential PGCs. OCT4 was detected in inner cell mass, epiblast, and mesoderm, and we found that OCT4 expression, in contrast...

  6. Bilateral congenital lacrimal fistulas in an adult as part of ectrodactyly-ectodermal dysplasia-clefting syndrome: A rare anomaly

    Directory of Open Access Journals (Sweden)

    Debangshu Ghosh

    2015-01-01

    Full Text Available Ectrodactyly-ectodermal dysplasia and clefting syndrome or "Lobster claw" deformity is a rare congenital anomaly that affects tissues of ectodermal and mesodermal origin. Nasolacrimal duct (NLD obstruction with or without atresia of lacrimal passage is a common finding of such a syndrome. The authors report here even a rarer presentation of the syndrome which manifested as bilateral NLD obstruction and lacrimal fistula along with cleft lip and palate, syndactyly affecting all four limbs, mild mental retardation, otitis media, and sinusitis. Lacrimal duct obstruction and fistula were managed successfully with endoscopic dacryocystorhinostomy (DCR which is a good alternative to lacrimal probing or open DCR in such a case.

  7. Gene transfer to pre-hematopoietic and committed hematopoietic precursors in the early mouse Yolk Sac: a comparative study between in situ electroporation and retroviral transduction

    Directory of Open Access Journals (Sweden)

    Lécluse Yann

    2007-07-01

    Full Text Available Abstract Background Hematopoietic development in vertebrate embryos results from the sequential contribution of two pools of precursors independently generated. While intra-embryonic precursors harbour the features of hematopoietic stem cells (HSC, precursors formed earlier in the yolk sac (YS display limited differentiation and self-renewal potentials. The mechanisms leading to the generation of the precursors in both sites are still largely unknown, as are the molecular basis underlying their different potential. A possible approach to assess the role of candidate genes is to transfer or modulate their expression/activity in both sites. We thus designed and compared transduction protocols to target either native extra-embryonic precursors, or hematopoietic precursors. Results One transduction protocol involves transient modification of gene expression through in situ electroporation of the prospective blood islands, which allows the evolution of transfected mesodermal cells in their "normal" environment, upon organ culture. Following in situ electroporation of a GFP reporter construct into the YS cavity of embryos at post-streak (mesodermal/pre-hematopoietic precursors or early somite (hematopoietic precursors stages, high GFP expression levels as well as a good preservation of cell viability is observed in YS explants. Moreover, the erythro-myeloid progeny typical of the YS arises from GFP+ mesodermal cells or hematopoietic precursors, even if the number of targeted precursors is low. The second approach, based on retroviral transduction allows a very efficient transduction of large precursor numbers, but may only be used to target 8 dpc YS hematopoietic precursors. Again, transduced cells generate a progeny quantitatively and qualitatively similar to that of control YS. Conclusion We thus provide two protocols whose combination may allow a thorough study of both early and late events of hematopoietic development in the murine YS. In situ

  8. Tamoxifen-dependent, inducible Bmp2CreER drives selective recombinase activity in early interdigital mesenchyme and digit collateral ligaments.

    Science.gov (United States)

    Huang, Bau-Lin; Mackem, Susan

    2015-01-01

    During limb development, the interdigital mesenchyme has been proposed to play a signaling role instructing morphogenesis of different digit types, as well as undergoing programmed cell death necessary to free digits in animals not adapted for swimming or flying. We have generated a conditional, tamoxifen-dependent Cre line, Bmp2CreER, which drives highly selective recombination restricted to the distal limb mesoderm, largely restricted to the interdigits, and selectively active in digit ligament but not tendon progenitors at later stages. The Bmp2CreER provides a valuable new tool to dissect roles of interdigital mesenchyme and potentially investigate divergence of ligament and tendon lineages.

  9. Human stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Aldahmash, Abdullah; Zaher, Walid; Al-Nbaheen, May

    2012-01-01

    Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self......-renewal and multi-lineage differentiation into mesoderm-type of cells, e.g., to osteoblasts, adipocytes, chondrocytes and possibly other cell types including hepatocytes and astrocytes. Due to their ease of culture and multipotentiality, hMSC are increasingly employed as a source for cells suitable for a number...

  10. Human bone-marrow-derived mesenchymal stem cells

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Abdallah, Basem M

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of cells present in bone-marrow stroma and the stroma of various organs with the capacity for mesoderm-like cell differentiation into, for example, osteoblasts, adipocytes, and chondrocytes. MSC are being introduced in the clinic for the treatment...... of a variety of clinical conditions. The aim of this review is to provide an update regarding the biology of MSC, their identification and culture, and mechanisms controlling their proliferation and differentiation. We also review the current status of their clinical use. Areas in which research is needed...

  11. MicroRNAs as Regulators of Adipogenic Differentiation of Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

    Hamam, Dana; Ali, Dalia; Kassem, Moustapha

    2015-01-01

    MicroRNAs (miRNAs) constitute complex regulatory network, fine tuning the expression of a myriad of genes involved in different biological and physiological processes, including stem cell differentiation. Mesenchymal stem cells (MSCs) are multipotent stem cells present in the bone marrow stroma......, and the stroma of many other tissues, and can give rise to a number of mesoderm-type cells including adipocytes and osteoblasts, which form medullary fat and bone tissues, respectively. The role of bone marrow fat in bone mass homeostasis is an area of intensive investigation with the aim of developing novel...

  12. Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

    Horwood, Nicole J.; Dazzi, Francesco; Zaher, Walid

    2012-01-01

    Mesenchymal stem cells (MSC) are stem cell populations present among the bone marrow stroma and a number of other tissues that are capable of multi-lineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. MSC provide supportive stroma for growth...... and differentiation of hematopoietic stem cells (HSC) and hematopoiesis. These cells have been described as important immunoregulators due to their ability to suppress T cells proliferation. MSC can also directly contribute to tissue repair by migrating to sites of injury and providing a source of cells...

  13. Radiological features of Goltz syndrome: Focal dermal hypoplasia. A report of two cases

    Energy Technology Data Exchange (ETDEWEB)

    Boothyrod, A.E.; Hall, C.M.

    1988-10-01

    Two female infants with Goltz syndrome (focal dermal hypoplasia) were recently investigated for severe feeding problems and failure to thrive. Both demonstrated severe skeletal malformations and marked gastrooesophageal reflux with laxity of the hiatus. One child (case 1) exhibited nasal regurgitation during feeding. Interestingly, both children had undergone surgery; Case 1 or a right parasagittal abdominal hernia associated with focal dermal hypoplasia of the abdominal wall and Case 2 for an exomphalos also associated with dermal hypoplasia. This observation suggests more widespread mesodermal abnormality. (orig./GDG).

  14. A report of three cases of neurofibromatosis in the head

    International Nuclear Information System (INIS)

    Shin, In Sook; Cho, Jeong Shin; Lee, Jang Yeol; Go, Jee Young; Kim, Sun Yong; Park, Chang Seo; Kim, Kee Deog

    1994-01-01

    Neurofibromatosis or Von Recklinghausen's disease is inherited as an autosomal dominant neuro-cutaneous systemic disease. It is characterized by multiple Cafe-au-lait spots, generalized cutaneous neurofibromas. It affects one in 3000 births. We observed the clinical, radiologic and histopathologic findings of 3 cases of neurofibromatosis and obtained following results. 1. All patients had multiple Cafe-au-lait spots and neurofibromas. 2. Two patients had radiographic changes of pressive erosion and mesodermal dysplasia. 3. Two patients had plexiform neurofibromas and 1 patient had diffuse neurofibromas. Conclusively, we classified these 3 cases as NF-I.

  15. Neurofibromatosis revisited: A pictorial review

    Directory of Open Access Journals (Sweden)

    Nausheen Khan

    2010-03-01

    Full Text Available Neurofibromatosis (or von Recklinghausen disease is a hereditary condition due to mesodermal and neuroectodermal dysplasia, eponymously named after the researcher who reported it in 1882. The disorder is transmitted as an autosomal dominant condition, but 50% of cases arise as spontaneous mutations. The incidence falls within the range 1:2 000 - 1:4 000, and has no gender bias. We present a series of images produced by different modalities that show lesions and pathologies that are characteristic of the disease.

  16. A report of three cases of neurofibromatosis in the head

    Energy Technology Data Exchange (ETDEWEB)

    Shin, In Sook; Cho, Jeong Shin; Lee, Jang Yeol; Go, Jee Young; Kim, Sun Yong; Park, Chang Seo; Kim, Kee Deog [Dept. of Dental Radiology, College of Dentistry, Yensei University, Seoul (Korea, Republic of)

    1994-02-15

    Neurofibromatosis or Von Recklinghausen's disease is inherited as an autosomal dominant neuro-cutaneous systemic disease. It is characterized by multiple Cafe-au-lait spots, generalized cutaneous neurofibromas. It affects one in 3000 births. We observed the clinical, radiologic and histopathologic findings of 3 cases of neurofibromatosis and obtained following results. 1. All patients had multiple Cafe-au-lait spots and neurofibromas. 2. Two patients had radiographic changes of pressive erosion and mesodermal dysplasia. 3. Two patients had plexiform neurofibromas and 1 patient had diffuse neurofibromas. Conclusively, we classified these 3 cases as NF-I.

  17. Solitary odontodysplasia: A rare entity

    Directory of Open Access Journals (Sweden)

    D Gurunathan

    2011-01-01

    Full Text Available Odontodysplasia is a rare, non-hereditary developmental anomaly affecting dental tissues derived from both the mesoderm and ectoderm which results in a bizarre clinical and radiographic appearance. Regional odontodysplasia describes the segmental and localized nature of the condition. Odontodysplasia occurring in a single tooth is a rare occurrence. A case of Solitary odontodysplasia in an eleven year and half old male whose chief complaint was the absence of eruption of permanent maxillary right central incisor teeth is presented. Clinical, radiographic and histological findings of a single tooth, odontodysplasia are described in this case report.

  18. Myogenesis in the sea urchin embryo: the molecular fingerprint of the myoblast precursors

    Science.gov (United States)

    2013-01-01

    Background In sea urchin larvae the circumesophageal fibers form a prominent muscle system of mesodermal origin. Although the morphology and later development of this muscle system has been well-described, little is known about the molecular signature of these cells or their precise origin in the early embryo. As an invertebrate deuterostome that is more closely related to the vertebrates than other commonly used model systems in myogenesis, the sea urchin fills an important phylogenetic gap and provides a unique perspective on the evolution of muscle cell development. Results Here, we present a comprehensive description of the development of the sea urchin larval circumesophageal muscle lineage beginning with its mesodermal origin using high-resolution localization of the expression of several myogenic transcriptional regulators and differentiation genes. A few myoblasts are bilaterally distributed at the oral vegetal side of the tip of the archenteron and first appear at the late gastrula stage. The expression of the differentiation genes Myosin Heavy Chain, Tropomyosin I and II, as well as the regulatory genes MyoD2, FoxF, FoxC, FoxL1, Myocardin, Twist, and Tbx6 uniquely identify these cells. Interestingly, evolutionarily conserved myogenic factors such as Mef2, MyoR and Six1/2 are not expressed in sea urchin myoblasts but are found in other mesodermal domains of the tip of the archenteron. The regulatory states of these domains were characterized in detail. Moreover, using a combinatorial analysis of gene expression we followed the development of the FoxF/FoxC positive cells from the onset of expression to the end of gastrulation. Our data allowed us to build a complete map of the Non-Skeletogenic Mesoderm at the very early gastrula stage, in which specific molecular signatures identify the precursors of different cell types. Among them, a small group of cells within the FoxY domain, which also express FoxC and SoxE, have been identified as plausible myoblast

  19. Myogenesis in the sea urchin embryo: the molecular fingerprint of the myoblast precursors.

    Science.gov (United States)

    Andrikou, Carmen; Iovene, Edmondo; Rizzo, Francesca; Oliveri, Paola; Arnone, Maria Ina

    2013-12-02

    In sea urchin larvae the circumesophageal fibers form a prominent muscle system of mesodermal origin. Although the morphology and later development of this muscle system has been well-described, little is known about the molecular signature of these cells or their precise origin in the early embryo. As an invertebrate deuterostome that is more closely related to the vertebrates than other commonly used model systems in myogenesis, the sea urchin fills an important phylogenetic gap and provides a unique perspective on the evolution of muscle cell development. Here, we present a comprehensive description of the development of the sea urchin larval circumesophageal muscle lineage beginning with its mesodermal origin using high-resolution localization of the expression of several myogenic transcriptional regulators and differentiation genes. A few myoblasts are bilaterally distributed at the oral vegetal side of the tip of the archenteron and first appear at the late gastrula stage. The expression of the differentiation genes Myosin Heavy Chain, Tropomyosin I and II, as well as the regulatory genes MyoD2, FoxF, FoxC, FoxL1, Myocardin, Twist, and Tbx6 uniquely identify these cells. Interestingly, evolutionarily conserved myogenic factors such as Mef2, MyoR and Six1/2 are not expressed in sea urchin myoblasts but are found in other mesodermal domains of the tip of the archenteron. The regulatory states of these domains were characterized in detail. Moreover, using a combinatorial analysis of gene expression we followed the development of the FoxF/FoxC positive cells from the onset of expression to the end of gastrulation. Our data allowed us to build a complete map of the Non-Skeletogenic Mesoderm at the very early gastrula stage, in which specific molecular signatures identify the precursors of different cell types. Among them, a small group of cells within the FoxY domain, which also express FoxC and SoxE, have been identified as plausible myoblast precursors. Together

  20. Vitamin D metabolism and effects on pluripotency genes and cell differentiation in testicular germ cell tumors in vitro and in vivo

    DEFF Research Database (Denmark)

    Blomberg Jensen, Martin; Jørgensen, Anne; Nielsen, John Erik

    2012-01-01

    TGCTs. VD metabolism diminished markedly during the malignant transformation from CIS to EC but was reestablished in differentiated components of nonseminomas, distinguished by coexpression of mesodermal markers and loss of OCT4. Subsequent in vitro studies confirmed that 1,25(OH)(2)D(3) (active VD...... xenografted into nude mice and treated with 1,25(OH)(2)D(3), which induced down-regulation of pluripotency factors but caused no significant reduction of tumor growth. During NTera2 tumor formation, down-regulation of VDR was observed, resulting in limited responsiveness to cholecalciferol and 1,25(OH)(2)D(3...

  1. The radiological features of Goltz syndrome: Focal dermal hypoplasia

    International Nuclear Information System (INIS)

    Boothyrod, A.E.; Hall, C.M.

    1988-01-01

    Two female infants with Goltz syndrome (focal dermal hypoplasia) were recently investigated for severe feeding problems and failure to thrive. Both demonstrated severe skeletal malformations and marked gastrooesophageal reflux with laxity of the hiatus. One child (case 1) exhibited nasal regurgitation during feeding. Interestingly, both children had undergone surgery; Case 1 or a right parasagittal abdominal hernia associated with focal dermal hypoplasia of the abdominal wall and Case 2 for an exomphalos also associated with dermal hypoplasia. This observation suggests more widespread mesodermal abnormality. (orig./GDG)

  2. Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock

    OpenAIRE

    Bessho, Yasumasa; Hirata, Hiromi; Masamizu, Yoshito; Kageyama, Ryoichiro

    2003-01-01

    Hes7, a bHLH gene essential for somitogenesis, displays cyclic expression of mRNA in the presomitic mesoderm (PSM). Here, we show that Hes7 protein is also expressed in a dynamic manner, which depends on proteasome-mediated degradation. Spatial comparison revealed that Hes7 and Lunatic fringe (Lfng) transcription occurs in the Hes7 protein-negative domains. Furthermore, Hes7 and Lfng transcription is constitutively up-regulated in the absence of Hes7 protein and down-regulated by stabi...

  3. Human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Abdallah, Basem; Kassem, Moustapha

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being...... introduced into clinical medicine in variety of applications and through different ways of administration. Here, we discuss approaches for isolation, characterization and directing differentiation of human mesenchymal stem cells (hMSC). An update of the current clinical use of the cells is also provided....

  4. Antero-posterior patterning of the vertebrate digestive tract: 40 years after Nicole Le Douarin's PhD thesis.

    Science.gov (United States)

    Grapin-Botton, Anne

    2005-01-01

    This review is dedicated to the work on chick digestive tract organogenesis that Nicole Le Douarin performed as a PhD student under the direction of Etienne Wolf. I discuss how she laid the grounds for future work by establishing fate maps at somitic stages, by describing morphogenetic movements between germ layers and by pointing to signaling events between endoderm and mesoderm. Her inspiring work was extended by others, in particular at the molecular level, leading to a better understanding of antero-posterior patterning in the digestive tract. Antero-posterior patterning of endoderm is initiated at gastrulation when future anterior and posterior endoderm ingress at different times and accordingly express different genes. Plasticity is however maintained at somite stages and even later, when organ primordia can be delineated. There is a cross-talk between endoderm and mesoderm and the two layers exchange instructive signals that induce specific antero-posterior identities as well as permissive signals required for organogenesis from previously patterned fields. Recent experiments suggest that several signaling molecules involved in neural tube antero-posterior patterning are also instrumental in the digestive tract including retinoic acid and FGF4.

  5. Lessons learned about adult kidney stem cells from the malpighian tubules of Drosophila.

    Science.gov (United States)

    Singh, Shree Ram; Hou, Steven X

    2008-04-01

    All multicellular organisms have a specialized organ to concentrate and excrete wastes from the body. The kidneys in vertebrates and the malpighian tubules in Drosophila accomplish these functions. Mammals and Drosophila share some similar features during renal tubular development. Vertebrate kidneys are derived through the mutual induction of the ureteric bud and metanephric mesoderm, whereas the malpighian tubules of Drosophila develop from the hindgut primordium and visceral mesoderm. The vertebrate kidney also has the capacity to recover and regenerate following episodes of acute injury. Previous studies suggest that stem cells and progenitor cells may be involved in the repair and regeneration of injured renal tissue. However, studies differ as to the source of the regenerating renal cells. Recently, multipotent stem cells in Drosophila malpighian tubules were identified, and it was demonstrated that several differentiated cells in the malpighian tubules arise from these stem cells. In this article, the current understanding of kidney development and stem cell fate in mammal and Drosophila is compared. Furthermore, the potential application of the adult renal stem cells in kidney repair and the treatment of kidney cancers are discussed.

  6. A systemic evaluation of cardiac differentiation from mRNA reprogrammed human induced pluripotent stem cells.

    Science.gov (United States)

    Mehta, Ashish; Verma, Vinod; Nandihalli, Manasi; Ramachandra, Chrishan J A; Sequiera, Glen L; Sudibyo, Yuliansa; Chung, Yingying; Sun, William; Shim, Winston

    2014-01-01

    Genetically unmodified cardiomyocytes mandated for cardiac regenerative therapy is conceivable by "foot-print free" reprogramming of somatic cells to induced pluripotent stem cells (iPSC). In this study, we report generation of foot-print free hiPSC through messenger RNA (mRNA) based reprograming. Subsequently, we characterize cardiomyocytes derived from these hiPSC using molecular and electrophysiological methods to characterize their applicability for regenerative medicine. Our results demonstrate that mRNA-iPSCs differentiate ontogenetically into cardiomyocytes with increased expression of early commitment markers of mesoderm, cardiac mesoderm, followed by cardiac specific transcriptional and sarcomeric structural and ion channel genes. Furthermore, these cardiomyocytes stained positively for sarcomeric and ion channel proteins. Based on multi-electrode array (MEA) recordings, these mRNA-hiPSC derived cardiomyocytes responded predictably to various pharmacologically active drugs that target adrenergic, sodium, calcium and potassium channels. The cardiomyocytes responded chronotropically to isoproterenol in a dose dependent manner, inotropic activity of nifidipine decreased spontaneous contractions. Moreover, Sotalol and E-4031 prolonged QT intervals, while TTX reduced sodium influx. Our results for the first time show a systemic evaluation based on molecular, structural and functional properties of cardiomyocytes differentiated from mRNA-iPSC. These results, coupled with feasibility of generating patient-specific iPSCs hold great promise for the development of large-scale generation of clinical grade cardiomyocytes for cardiac regenerative medicine.

  7. Epigenetic Reprogramming of Human Embryonic Stem Cells into Skeletal Muscle Cells and Generation of Contractile Myospheres

    Directory of Open Access Journals (Sweden)

    Sonia Albini

    2013-03-01

    Full Text Available Direct generation of a homogeneous population of skeletal myoblasts from human embryonic stem cells (hESCs and formation of three-dimensional contractile structures for disease modeling in vitro are current challenges in regenerative medicine. Previous studies reported on the generation of myoblasts from ESC-derived embryoid bodies (EB, but not from undifferentiated ESCs, indicating the requirement for mesodermal transition to promote skeletal myogenesis. Here, we show that selective absence of the SWI/SNF component BAF60C (encoded by SMARCD3 confers on hESCs resistance to MyoD-mediated activation of skeletal myogenesis. Forced expression of BAF60C enables MyoD to directly activate skeletal myogenesis in hESCs by instructing MyoD positioning and allowing chromatin remodeling at target genes. BAF60C/MyoD-expressing hESCs are epigenetically committed myogenic progenitors, which bypass the mesodermal requirement and, when cultured as floating clusters, give rise to contractile three-dimensional myospheres composed of skeletal myotubes. These results identify BAF60C as a key epigenetic determinant of hESC commitment to the myogenic lineage and establish the molecular basis for the generation of hESC-derived myospheres exploitable for “disease in a dish” models of muscular physiology and dysfunction.

  8. A systemic evaluation of cardiac differentiation from mRNA reprogrammed human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Ashish Mehta

    Full Text Available Genetically unmodified cardiomyocytes mandated for cardiac regenerative therapy is conceivable by "foot-print free" reprogramming of somatic cells to induced pluripotent stem cells (iPSC. In this study, we report generation of foot-print free hiPSC through messenger RNA (mRNA based reprograming. Subsequently, we characterize cardiomyocytes derived from these hiPSC using molecular and electrophysiological methods to characterize their applicability for regenerative medicine. Our results demonstrate that mRNA-iPSCs differentiate ontogenetically into cardiomyocytes with increased expression of early commitment markers of mesoderm, cardiac mesoderm, followed by cardiac specific transcriptional and sarcomeric structural and ion channel genes. Furthermore, these cardiomyocytes stained positively for sarcomeric and ion channel proteins. Based on multi-electrode array (MEA recordings, these mRNA-hiPSC derived cardiomyocytes responded predictably to various pharmacologically active drugs that target adrenergic, sodium, calcium and potassium channels. The cardiomyocytes responded chronotropically to isoproterenol in a dose dependent manner, inotropic activity of nifidipine decreased spontaneous contractions. Moreover, Sotalol and E-4031 prolonged QT intervals, while TTX reduced sodium influx. Our results for the first time show a systemic evaluation based on molecular, structural and functional properties of cardiomyocytes differentiated from mRNA-iPSC. These results, coupled with feasibility of generating patient-specific iPSCs hold great promise for the development of large-scale generation of clinical grade cardiomyocytes for cardiac regenerative medicine.

  9. Sirenomelia phenotype in bmp7;shh compound mutants: a novel experimental model for studies of caudal body malformations.

    Directory of Open Access Journals (Sweden)

    Carlos Garrido-Allepuz

    Full Text Available Sirenomelia is a severe congenital malformation of the lower body characterized by the fusion of the legs into a single lower limb. This striking external phenotype consistently associates severe visceral abnormalities, most commonly of the kidneys, intestine, and genitalia that generally make the condition lethal. Although the causes of sirenomelia remain unknown, clinical studies have yielded two major hypotheses: i a primary defect in the generation of caudal mesoderm, ii a primary vascular defect that leaves the caudal part of the embryo hypoperfused. Interestingly, Sirenomelia has been shown to have a genetic basis in mice, and although it has been considered a sporadic condition in humans, recently some possible familial cases have been reported. Here, we report that the removal of one or both functional alleles of Shh from the Bmp7-null background leads to a sirenomelia phenotype that faithfully replicates the constellation of external and internal malformations, typical of the human condition. These mutants represent an invaluable model in which we have analyzed the pathogenesis of sirenomelia. We show that the signaling defect predominantly impacts the morphogenesis of the hindgut and the development of the caudal end of the dorsal aortas. The deficient formation of ventral midline structures, including the interlimb mesoderm caudal to the umbilicus, leads to the approximation and merging of the hindlimb fields. Our study provides new insights for the understanding of the mechanisms resulting in caudal body malformations, including sirenomelia.

  10. Targeted disruption of cubilin reveals essential developmental roles in the structure and function of endoderm and in somite formation

    Directory of Open Access Journals (Sweden)

    Cooley Marion A

    2006-06-01

    Full Text Available Abstract Background Cubilin is a peripheral membrane protein that interacts with the integral membrane proteins megalin and amnionless to mediate ligand endocytosis by absorptive epithelia such as the extraembryonic visceral endoderm (VE. Results Here we report the effects of the genetic deletion of cubilin on mouse embryonic development. Cubilin gene deletion is homozygous embryonic lethal with death occurring between 7.5–13.5 days post coitum (dpc. Cubilin-deficient embryos display developmental retardation and do not advance morphologically beyond the gross appearance of wild-type 8–8.5 dpc embryos. While mesodermal structures such as the allantois and the heart are formed in cubilin mutants, other mesoderm-derived tissues are anomalous or absent. Yolk sac blood islands are formed in cubilin mutants but are unusually large, and the yolk sac blood vessels fail to undergo remodeling. Furthermore, somite formation does not occur in cubilin mutants. Morphological abnormalities of endoderm occur in cubilin mutants and include a stratified epithelium in place of the normally simple columnar VE epithelium and a stratified cuboidal epithelium in place of the normally simple squamous epithelium of the definitive endoderm. Cubilin-deficient VE is also functionally defective, unable to mediate uptake of maternally derived high-density lipoprotein (HDL. Conclusion In summary, cubilin is required for embryonic development and is essential for the formation of somites, definitive endoderm and VE and for the absorptive function of VE including the process of maternal-embryo transport of HDL.

  11. The Drosophila Transcription Factors Tinman and Pannier Activate and Collaborate with Myocyte Enhancer Factor-2 to Promote Heart Cell Fate.

    Directory of Open Access Journals (Sweden)

    TyAnna L Lovato

    Full Text Available Expression of the MADS domain transcription factor Myocyte Enhancer Factor 2 (MEF2 is regulated by numerous and overlapping enhancers which tightly control its transcription in the mesoderm. To understand how Mef2 expression is controlled in the heart, we identified a late stage Mef2 cardiac enhancer that is active in all heart cells beginning at stage 14 of embryonic development. This enhancer is regulated by the NK-homeodomain transcription factor Tinman, and the GATA transcription factor Pannier through both direct and indirect interactions with the enhancer. Since Tinman, Pannier and MEF2 are evolutionarily conserved from Drosophila to vertebrates, and since their vertebrate homologs can convert mouse fibroblast cells to cardiomyocytes in different activator cocktails, we tested whether over-expression of these three factors in vivo could ectopically activate known cardiac marker genes. We found that mesodermal over-expression of Tinman and Pannier resulted in approximately 20% of embryos with ectopic Hand and Sulphonylurea receptor (Sur expression. By adding MEF2 alongside Tinman and Pannier, a dramatic expansion in the expression of Hand and Sur was observed in almost all embryos analyzed. Two additional cardiac markers were also expanded in their expression. Our results demonstrate the ability to initiate ectopic cardiac fate in vivo by the combination of only three members of the conserved Drosophila cardiac transcription network, and provide an opportunity for this genetic model system to be used to dissect the mechanisms of cardiac specification.

  12. Expression of GATA and POU transcription factors during the development of the planktotrophic trochophore of the polychaete serpulid Hydroides elegans.

    Science.gov (United States)

    Wong, Kimberly Suk-Ying; Arenas-Mena, Cesar

    2016-07-01

    The expression of transcription factors with endodermal and mesodermal roles in bilaterians is characterized during the development of Hydroides elegans, a serpulid polychaete with planktotrophic trochophore. GATA 4/5/6 is expressed in endodermal and mesodermal precursors during embryogenesis and in the midgut of trochophore larvae. HeGATA1/2/3a is expressed in animal hemisphere blastomeres 1d121 and 1d122, in dorsal ectoderm and in 4d endomesodermal derivatives that maintain their expression in trochophore larvae. HeGATA1/2/3b is not expressed during embryogenesis, but in several regions of the larva during postembryonic development. During very early gastrulation, Brn1/2/4 is first expressed in cells associated with the prospective oral/foregut side of the blastopore, and during larval development in 4d blastomere descendants. Comparison with orthologs in other metazoans suggests ancestral expression of GATA4/5/6 in the midgut of the last common ancestor of protostomes and deuterostomes. The conserved expression of Brn1/2/4 in the foregut precursors of Hydroides and sea urchins suggests an ancestral role in patterning the tripartite gut of planktotrophic larvae. Broader analysis of these and other regulatory genes reveals variability of developmental gene expression among polychaetes with lecithotrophic larvae, suggesting that they are evolutionarily derived from polychaetes with planktotrophic larvae. © 2016 Wiley Periodicals, Inc.

  13. Pitx2-mediated cardiac outflow tract remodeling.

    Science.gov (United States)

    Ma, Hsiao-Yen; Xu, Jun; Eng, Diana; Gross, Michael K; Kioussi, Chrissa

    2013-05-01

    Heart morphogenesis involves sequential anatomical changes from a linear tube of a single channel peristaltic pump to a four-chamber structure with two channels controlled by one-way valves. The developing heart undergoes continuous remodeling, including septation. Pitx2-null mice are characterized by cardiac septational defects of the atria, ventricles, and outflow tract. Pitx2-null mice also exhibited a short outflow tract, including unseptated conus and deformed endocardial cushions. Cushions were characterized with a jelly-like structure, rather than the distinct membrane-looking leaflets, indicating that endothelial mesenchymal transition was impaired in Pitx2(-/-) embryos. Mesoderm cells from the branchial arches and neural crest cells from the otic region contribute to the development of the endocardial cushions, and both were reduced in number. Members of the Fgf and Bmp families exhibited altered expression levels in the mutants. We suggest that Pitx2 is involved in the cardiac outflow tract septation by promoting and/or maintaining the number and the remodeling process of the mesoderm progenitor cells. Pitx2 influences the expression of transcription factors and signaling molecules involved in the differentiation of the cushion mesenchyme during heart development. Copyright © 2013 Wiley Periodicals, Inc.

  14. Early development of coelomic structures in an echinoderm larva and a similarity with coelomic structures in a chordate embryo.

    Science.gov (United States)

    Morris, Valerie B

    2012-11-01

    Early coelomic development in the abbreviated development of the sea urchin Holopneustes purpurescens is described and then used in a comparison with coelomic development in chordate embryos to support homology between a single arm of the five-armed radial body plan of an echinoderm and the single bilateral axis of a chordate. The homology depends on a positional similarity between the origin of the hydrocoele in echinoderm development and the origin of the notochord in chordate development, and a positional similarity between the respective origins of the coelomic mesoderm and chordate mesoderm in echinoderm and chordate development. The hydrocoele is homologous with the notochord and the secondary podia are homologous with the somites. The homology between a single echinoderm arm and the chordate axis becomes clear when the aboral to oral growth from the archenteron in the echinoderm larva is turned anteriorly, more in line with the anterior-posterior axis of the early zygote. A dorsoventral axis inversion in chordates is not required in the proposed homology.

  15. Expression of wnt and frizzled genes during early sea star development.

    Science.gov (United States)

    McCauley, Brenna S; Akyar, Eda; Filliger, Laura; Hinman, Veronica F

    2013-12-01

    The Wnt signaling pathway is highly conserved across metazoa and has pleiotropic functions in the development of many animals. Binding of a secreted Wnt ligand to its Frizzled (Fz) receptor activates Dishevelled, which then drives one of three major signaling cascades, canonical (β-catenin), calcium, or planar cell polarity signaling. These pathways have distinct developmental effects and function in different processes in different organisms. Here we report the expression of six wnt and three fz genes during embryogenesis of the sea star, Patiria miniata, as a first step in uncovering the roles of Wnt signaling in the development of this organism. wnt3, wnt4, wnt8, and wnt16 are expressed in nested domains in the endoderm and lateral ectoderm from blastula through late gastrula stages; wnt2 and wnt5 are expressed in the mesoderm and anterior endoderm. Expression of different fz paralogs is detected in the mesoderm; posterior endoderm and ectoderm; and anterior ectoderm. Taken together, this suggests that Wnt signaling can occur throughout most of the embryo and may therefore play multiple roles during sea star development. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Dose-dependent nuclear β-catenin response segregates endomesoderm along the sea star primary axis.

    Science.gov (United States)

    McCauley, Brenna S; Akyar, Eda; Saad, H Rosa; Hinman, Veronica F

    2015-01-01

    In many invertebrates, the nuclearization of β-catenin at one pole of the embryo initiates endomesoderm specification. An intriguing possibility is that a gradient of nuclear β-catenin (nβ-catenin), similar to that operating in vertebrate neural tube patterning, functions to distinguish cell fates in invertebrates. To test this hypothesis, we determined the function of nβ-catenin during the early development of the sea star, which undergoes a basal deuterostomal mode of embryogenesis. We show that low levels of nβ-catenin activity initiate bra, which is expressed in the future posterior endoderm-fated territory; intermediate levels are required for expression of foxa and gata4/5/6, which are later restricted to the endoderm; and activation of ets1 and erg in the mesoderm-fated territory requires the highest nβ-catenin activity. Transcription factors acting downstream of high nβ-catenin segregate the endoderm/mesoderm boundary, which is further reinforced by Delta/Notch signaling. Significantly, therefore, in sea stars, endomesoderm segregation arises through transcriptional responses to levels of nβ-catenin activity. Here, we describe the first empirical evidence of a dose-dependent response to a dynamic spatiotemporal nβ-catenin activity that patterns cell fates along the primary axis in an invertebrate. © 2015. Published by The Company of Biologists Ltd.

  17. Two novel EGFP insertion alleles reveal unique aspects of Pax2 function in embryonic and adult kidneys.

    Science.gov (United States)

    Soofi, Abdul; Levitan, Inna; Dressler, Gregory R

    2012-05-01

    The Pax2 gene encodes a DNA binding protein with multiple functions in the developing intermediate mesoderm and urogenital tract. Loss of Pax2 in mice results in the complete absence of kidneys, ureters, and sex specific epithelial structures derived from the intermediate mesoderm in both males and females. In this report, we describe two new alleles of Pax2 created by inserting the enhanced green fluorescent protein coding region into the 5' untranslated leader sequence. One allele is a hypomorph that generates less protein and exhibits structural defects in kidneys and ureters upon homozygosity. A second allele is a true null that can be used to image Pax2 expressing cells in a mutant background. Organ culture and embryo analyses point to a loss of epithelial cell polarity and increased mobility in cells that have deleted Pax2 function. These experiments provide new insight into the role of Pax2 protein levels in determining correct renal architecture and cell fate. These new Pax2 alleles are valuable genetic reagents for in vivo studies of urogenital development. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Ultrastructure of male reproductive accessory glands and ejaculatory duct in the Queensland fruit fly, Bactrocera tryoni (Diptera: Tephritidae).

    Science.gov (United States)

    Radhakrishnan, Preethi; Marchini, Daniela; Taylor, Phillip W

    2009-05-01

    Ultrastructure of male reproductive accessory glands and ejaculatory duct in the Queensland fruit fly (Q-fly), Bactrocera tryoni, were investigated and compared with those of other tephritid flies. Male accessory glands were found to comprise one pair of mesodermic glands and three pairs of ectodermic glands. The mesodermic accessory glands consist of muscle-lined, binucleate epithelial cells, which are highly microvillated and extrude electron-dense secretions by means of macroapocrine transport into a central lumen. The ectodermic accessory glands consist of muscle-lined epithelial cells which have wide subcuticular cavities, lined with microvilli. The electron-transparent secretions from these glands are first extruded into the cavities and then forced out through small pores of the cuticle into the gland lumen. Secretions from the two types of accessory glands then flow into the ejaculatory duct, which is highly muscular, with epithelial cells rich in rough endoplasmic reticulum and lined with a thick, deeply invaginated cuticle. While there are some notable differences, reproductive accessory glands of male Q-flies generally resemble those of the olive fruitfly, Bactrocera oleae, and to a lesser extent the Mediterranean fruit fly, Ceratitis capitata.

  19. The Expression of Insulin-like Growth Factor and Insulin-like Growth Factor Binding Protein mRNAs in Mouse Placenta

    DEFF Research Database (Denmark)

    Carter, Anthony M.; Nygard, K.; Mazzuca, D.M.

    2006-01-01

    RNA weakly. The endothelium of maternal blood vessels in decidua expressed IGFBP-3 and -5 mRNAs, and some deeper vessels expressed IGFBP-4 mRNA. In the yolk sac, IGF-II mRNA was expressed in endoderm and mesoderm, whereas IGFBP-1, -2 and -4 mRNAs were expressed only in endoderm, and IGFBP-4 mRNA in mesoderm......, later strongly in glycogen cells and variably in giant cells. IGFBP-2 mRNA was expressed weakly in spongiotrophoblasts and glycogen cells. IGFBP-2, -5 and -6 mRNAs were detected in the stroma of the metrial gland. Myometrium expressed IGFBP-2 mRNA strongly, IGFBP-6 mRNA moderately and IGFBP-5 m...... in endothelium of maternal blood vessels, and IGFBP-2 and -6 mRNAs in myometrium, where IGFBPs may play a critical role in regulating trophoblast invasion. These findings suggest possible biological roles of the peptides at the feto-maternal interface....

  20. Differentiation defect in neural crest-derived smooth muscle cells in patients with aortopathy associated with bicuspid aortic valves

    Directory of Open Access Journals (Sweden)

    Jiao Jiao

    2016-08-01

    Full Text Available Individuals with bicuspid aortic valves (BAV are at a higher risk of developing thoracic aortic aneurysms (TAA than patients with trileaflet aortic valves (TAV. The aneurysms associated with BAV most commonly involve the ascending aorta and spare the descending aorta. Smooth muscle cells (SMCs in the ascending and descending aorta arise from neural crest (NC and paraxial mesoderm (PM, respectively. We hypothesized defective differentiation of the neural crest stem cells (NCSCs-derived SMCs but not paraxial mesoderm cells (PMCs-derived SMCs contributes to the aortopathy associated with BAV. When induced pluripotent stem cells (iPSCs from BAV/TAA patients were differentiated into NCSC-derived SMCs, these cells demonstrated significantly decreased expression of marker of SMC differentiation (MYH11 and impaired contraction compared to normal control. In contrast, the PMC-derived SMCs were similar to control cells in these aspects. The NCSC-SMCs from the BAV/TAA also showed decreased TGF-β signaling based on phosphorylation of SMAD2, and increased mTOR signaling. Inhibition of mTOR pathway using rapamycin rescued the aberrant differentiation. Our data demonstrates that decreased differentiation and contraction of patient's NCSC-derived SMCs may contribute to that aortopathy associated with BAV.

  1. Transcriptome analysis of primary bovine extra-embryonic cultured cells

    Directory of Open Access Journals (Sweden)

    Séverine A. Degrelle

    2015-12-01

    Full Text Available The dataset described in this article pertains to the article by Hue et al. (2015 entitled “Primary bovine extra-embryonic cultured cells: A new resource for the study of in vivo peri-implanting phenotypes and mesoderm formation” [1]. In mammals, extra-embryonic tissues are essential to support not only embryo patterning but also embryo survival, especially in late implanting species. These tissues are composed of three cell types: trophoblast (bTCs, endoderm (bXECs and mesoderm (bXMCs. Until now, it is unclear how these cells interact. In this study, we have established primary cell cultures of extra-embryonic tissues from bovine embryos collected at day-18 after artificial insemination. We used our homemade bovine 10K array (GPL7417 to analyze the gene expression profiles of these primary extra-embryonic cultured cells compared to the corresponding cells from in vivo micro-dissected embryos. Here, we described the experimental design, the isolation of bovine extra-embryonic cell types as well as the microarray expression analysis. The dataset has been deposited in Gene Expression Omnibus (GEO (accession number GSE52967. Finally, these primary cell cultures were a powerful tool to start studying their cellular properties, and will further allow in vitro studies on cellular interactions among extra-embryonic tissues, and potentially between extra-embryonic vs embryonic tissues.

  2. Microfluidic-based patterning of embryonic stem cells for in vitro development studies.

    Science.gov (United States)

    Suri, Shalu; Singh, Ankur; Nguyen, Anh H; Bratt-Leal, Andres M; McDevitt, Todd C; Lu, Hang

    2013-12-07

    In vitro recapitulation of mammalian embryogenesis and examination of the emerging behaviours of embryonic structures require both the means to engineer complexity and accurately assess phenotypes of multicellular aggregates. Current approaches to study multicellular populations in 3D configurations are limited by the inability to create complex (i.e. spatially heterogeneous) environments in a reproducible manner with high fidelity thus impeding the ability to engineer microenvironments and combinations of cells with similar complexity to that found during morphogenic processes such as development, remodelling and wound healing. Here, we develop a multicellular embryoid body (EB) fusion technique as a higher-throughput in vitro tool, compared to a manual assembly, to generate developmentally relevant embryonic patterns. We describe the physical principles of the EB fusion microfluidic device design; we demonstrate that >60 conjoined EBs can be generated overnight and emulate a development process analogous to mouse gastrulation during early embryogenesis. Using temporal delivery of bone morphogenic protein 4 (BMP4) to embryoid bodies, we recapitulate embryonic day 6.5 (E6.5) during mouse embryo development with induced mesoderm differentiation in murine embryonic stem cells leading to expression of Brachyury-T-green fluorescent protein (T-GFP), an indicator of primitive streak development and mesoderm differentiation during gastrulation. The proposed microfluidic approach could be used to manipulate hundreds or more of individual embryonic cell aggregates in a rapid fashion, thereby allowing controlled differentiation patterns in fused multicellular assemblies to generate complex yet spatially controlled microenvironments.

  3. Smoc2 modulates embryonic myelopoiesis during zebrafish development.

    Science.gov (United States)

    Mommaerts, Hendrik; Esguerra, Camila V; Hartmann, Ursula; Luyten, Frank P; Tylzanowski, Przemko

    2014-11-01

    SMOC2 is a member of the BM-40 (SPARC) family of matricellular proteins, reported to influence signaling in the extracellular compartment. In mice, Smoc2 is expressed in many different tissues and was shown to enhance the response to angiogenic growth factors, mediate cell adhesion, keratinocyte migration, and metastasis. Additionally, SMOC2 is associated with vitiligo and craniofacial and dental defects. The function of Smoc2 during early zebrafish development has not been determined to date. In pregastrula zebrafish embryos, smoc2 is expressed ubiquitously. As development progresses, the expression pattern becomes more anteriorly restricted. At the onset of blood cell circulation, smoc2 morphants presented a mild ventralization of posterior structures. Molecular analysis of the smoc2 morphants indicated myelopoietic defects in the rostral blood islands during segmentation stages. Hemangioblast development and further specification of the myeloid progenitor cells were shown to be impaired. Additional experiments indicated that Bmp target genes were down-regulated in smoc2 morphants. Our findings reveal that Smoc2 is an essential player in the development of myeloid cells of the anterior lateral plate mesoderm during embryonic zebrafish development. Furthermore, our data show that Smoc2 affects the transcription of Bmp target genes without affecting initial dorsoventral patterning or mesoderm development. Copyright © 2014 Wiley Periodicals, Inc.

  4. The gastrocoel roof plate in embryos of different frogs.

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    Sáenz-Ponce, Natalia; Santillana-Ortiz, Juan-Diego; del Pino, Eugenia M

    2012-02-01

    The morphology of the gastrocoel roof plate and the presence of cilia in this structure were examined in embryos of four species of frogs. Embryos of Ceratophrys stolzmanni (Ceratophryidae) and Engystomops randi (Leiuperidae) develop rapidly, provide comparison for the analysis of gastrocoel roof plate development in the slow-developing embryos of Epipedobates machalilla (Dendrobatidae) and Gastrotheca riobambae (Hemiphractidae). Embryos of the analyzed frogs develop from eggs of different sizes, and display different reproductive and developmental strategies. In particular, dorsal convergence and extension and archenteron elongation begin during gastrulation in embryos of rapidly developing frogs, as in Xenopus laevis. In contrast, cells that involute during gastrulation are stored in the large circumblastoporal collar that develops around the closed blastopore in embryos of slow-developing frogs. Dorsal convergence and extension only start after blastopore closure in slow-developing frog embryos. However, in the neurulae, a gastrocoel roof plate develops, despite the accumulation of superficial mesodermal cells in the circumblastoporal collar. Embryos of all four species develop a ciliated gastrocoel roof plate at the beginning of neurulation. Accordingly, fluid-flow across the gastrocoel roof plate is likely the mechanism of left-right asymmetry patterning in these frogs, as in X. laevis and other vertebrates. A ciliated gastrocoel roof plate, with a likely origin as superficial mesoderm, is conserved in frogs belonging to four different families and with different modes of gastrulation. Copyright © 2011 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  5. [The development of the mycetome in the embryo of Euscelis plebejus Fall. (Homoptera-Cicadina)].

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    Körner, Helge Klaus

    1969-03-01

    The egg of the leafhopper Euscelis plebejus contains 2 types of symbiontic bacteria classified by MüLLER (1949) as t- and a-symbionts. They are lodged near the posterior egg pole as a nearly spherical mass surrounded by periplasm. During anatrepsis of the germ band the volume of the symbiont mass increases considerably. At the same time the a-symbionts are taken up by primary a-mycetocytes which then form a spherical layer around the as yet extracellular mass of t-symbionts. When the mesoderm of the abdominal segments starts to differentiate into organ primordia, a cluster of presumably polyploid mesoderm cells leaves the 2nd abdominal segment and migrates towards the 5th and 6th abdominal segments where the symbionts are lodged. There these cells are filled with the t-symbionts which they harbour through all further stages of embryonic and postembryonic life. The a-symbionts before katatrepsis of the germ band appear to be taken over by a second type of a-mycetocyte which stems from the genital ridge of the 4th-6th abdominal segments and as a rule is binucleate. During and after katatrepsis the t-mycetocytes and secondary a-mycetocytes migrate from their medial position to the lateral walls of the abdomen where they form one compound mycetome on each side.

  6. Essential role of chromatin remodeling protein Bptf in early mouse embryos and embryonic stem cells.

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    Joseph Landry

    2008-10-01

    Full Text Available We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor, the largest subunit of NURF (Nucleosome Remodeling Factor in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8.5. Histological analyses of lineage markers show that Bptf(-/- embryos implant but fail to establish a functional distal visceral endoderm. Microarray analysis at early stages of differentiation has identified Bptf-dependent gene targets including homeobox transcriptions factors and genes essential for the development of ectoderm, mesoderm, and both definitive and visceral endoderm. Differentiation of Bptf(-/- embryonic stem cell lines into embryoid bodies revealed its requirement for development of mesoderm, endoderm, and ectoderm tissue lineages, and uncovered many genes whose activation or repression are Bptf-dependent. We also provide functional and physical links between the Bptf-containing NURF complex and the Smad transcription factors. These results suggest that Bptf may co-regulate some gene targets of this pathway, which is essential for establishment of the visceral endoderm. We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo.

  7. The migrations of Drosophila muscle founders and primordial germ cells are interdependent.

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    Stepanik, Vincent; Dunipace, Leslie; Bae, Young-Kyung; Macabenta, Frank; Sun, Jingjing; Trisnadi, Nathanie; Stathopoulos, Angelike

    2016-09-01

    Caudal visceral mesoderm (CVM) cells migrate from posterior to anterior of the Drosophila embryo as two bilateral streams of cells to support the specification of longitudinal muscles along the midgut. To accomplish this long-distance migration, CVM cells receive input from their environment, but little is known about how this collective cell migration is regulated. In a screen we found that wunen mutants exhibit CVM cell migration defects. Wunens are lipid phosphate phosphatases known to regulate the directional migration of primordial germ cells (PGCs). PGC and CVM cell types interact while PGCs are en route to the somatic gonadal mesoderm, and previous studies have shown that CVM impacts PGC migration. In turn, we found here that CVM cells exhibit an affinity for PGCs, localizing to the position of PGCs whether mislocalized or trapped in the endoderm. In the absence of PGCs, CVM cells exhibit subtle changes, including more cohesive movement of the migrating collective, and an increased number of longitudinal muscles is found at anterior sections of the larval midgut. These data demonstrate that PGC and CVM cell migrations are interdependent and suggest that distinct migrating cell types can coordinately influence each other to promote effective cell migration during development. © 2016. Published by The Company of Biologists Ltd.

  8. Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile.

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    Sugawa, Fumihiro; Araúzo-Bravo, Marcos J; Yoon, Juyong; Kim, Kee-Pyo; Aramaki, Shinya; Wu, Guangming; Stehling, Martin; Psathaki, Olympia E; Hübner, Karin; Schöler, Hans R

    2015-04-15

    Primordial germ cells (PGCs) develop only into sperm and oocytes in vivo. The molecular mechanisms underlying human PGC specification are poorly understood due to inaccessibility of cell materials and lack of in vitro models for tracking the earliest stages of germ cell development. Here, we describe a defined and stepwise differentiation system for inducing pre-migratory PGC-like cells (PGCLCs) from human pluripotent stem cells (PSCs). In response to cytokines, PSCs differentiate first into a heterogeneous mesoderm-like cell population and then into PGCLCs, which exhibit minimal PRDM14 expression. PGC specification in humans is similar to the murine process, with the sequential activation of mesodermal and PGC genes, and the suppression of neural induction and of de novo DNA methylation, suggesting that human PGC formation is induced via epigenesis, the process of germ cell specification via inductive signals from surrounding somatic cells. This study demonstrates that PGC commitment in humans shares key features with that of the mouse, but also highlights key differences, including transcriptional regulation during the early stage of human PGC development (3-6 weeks). A more comprehensive understanding of human germ cell development may lead to methodology for successfully generating PSC-derived gametes for reproductive medicine. © 2015 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  9. Clarification of mural cell coverage of vascular endothelial cells by live imaging of zebrafish.

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    Ando, Koji; Fukuhara, Shigetomo; Izumi, Nanae; Nakajima, Hiroyuki; Fukui, Hajime; Kelsh, Robert N; Mochizuki, Naoki

    2016-04-15

    Mural cells (MCs) consisting of vascular smooth muscle cells and pericytes cover the endothelial cells (ECs) to regulate vascular stability and homeostasis. Here, we clarified the mechanism by which MCs develop and cover ECs by generating transgenic zebrafish lines that allow live imaging of MCs and by lineage tracing in vivo To cover cranial vessels, MCs derived from either neural crest cells or mesoderm emerged around the preformed EC tubes, proliferated and migrated along EC tubes. During their migration, the MCs moved forward by extending their processes along the inter-EC junctions, suggesting a role for inter-EC junctions as a scaffold for MC migration. In the trunk vasculature, MCs derived from mesoderm covered the ventral side of the dorsal aorta (DA), but not the posterior cardinal vein. Furthermore, the MCs migrating from the DA or emerging around intersegmental vessels (ISVs) preferentially covered arterial ISVs rather than venous ISVs, indicating that MCs mostly cover arteries during vascular development. Thus, live imaging and lineage tracing enabled us to clarify precisely how MCs cover the EC tubes and to identify the origins of MCs. © 2016. Published by The Company of Biologists Ltd.

  10. Evo-engineering and the cellular and molecular origins of the vertebrate spinal cord.

    Science.gov (United States)

    Steventon, Ben; Martinez Arias, Alfonso

    2017-12-01

    The formation of the spinal cord during early embryonic development in vertebrate embryos is a continuous process that begins at gastrulation and continues through to the completion of somitogenesis. Despite the conserved usage of patterning mechanisms and gene regulatory networks that act to generate specific spinal cord progenitors, there now exists two seemingly disparate models to account for their action. In the first, a posteriorly localized signalling source transforms previously anterior-specified neural plate into the spinal cord. In the second, a population of bipotent stem cells undergo continuous self-renewal and differentiation to progressively lay down the spinal cord and axial mesoderm by posterior growth. Whether this represents fundamental differences between the experimental model organisms utilised in the generation of these models remains to be addressed. Here we review lineage studies across four key vertebrate models: mouse, chicken, Xenopus and zebrafish and relate them to the underlying gene regulatory networks that are known to be required for spinal cord formation. We propose that by applying a dynamical systems approach to understanding how distinct neural and mesodermal fates arise from a bipotent progenitor pool, it is possible to begin to understand how differences in the dynamical cell behaviours such as proliferation rates and cell movements can map onto conserved regulatory networks to generate diversity in the timing of tissue generation and patterning during development. Copyright © 2017. Published by Elsevier Inc.

  11. Anatomical integration of the sacral-hindlimb unit coordinated by GDF11 underlies variation in hindlimb positioning in tetrapods.

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    Matsubara, Yoshiyuki; Hirasawa, Tatsuya; Egawa, Shiro; Hattori, Ayumi; Suganuma, Takaya; Kohara, Yuhei; Nagai, Tatsuya; Tamura, Koji; Kuratani, Shigeru; Kuroiwa, Atsushi; Suzuki, Takayuki

    2017-09-01

    Elucidating how body parts from different primordia are integrated during development is essential for understanding the nature of morphological evolution. In tetrapod evolution, while the position of the hindlimb has diversified along with the vertebral formula, the mechanism responsible for this coordination has not been well understood. However, this synchronization suggests the presence of an evolutionarily conserved developmental mechanism that coordinates the positioning of the hindlimb skeleton derived from the lateral plate mesoderm with that of the sacral vertebrae derived from the somites. Here we show that GDF11 secreted from the posterior axial mesoderm is a key factor in the integration of sacral vertebrae and hindlimb positioning by inducing Hox gene expression in two different primordia. Manipulating the onset of GDF11 activity altered the position of the hindlimb in chicken embryos, indicating that the onset of Gdf11 expression is responsible for the coordinated positioning of the sacral vertebrae and hindlimbs. Through comparative analysis with other vertebrate embryos, we also show that each tetrapod species has a unique onset timing of Gdf11 expression, which is tightly correlated with the anteroposterior levels of the hindlimb bud. We conclude that the evolutionary diversity of hindlimb positioning resulted from heterochronic shifts in Gdf11 expression, which led to coordinated shifts in the sacral-hindlimb unit along the anteroposterior axis.

  12. Adipose-derived stem and stromal cells for cell-based therapy: current status of preclinical studies and clinical trials.

    Science.gov (United States)

    Mizuno, Hiroshi

    2010-08-01

    The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift that may provide alternative therapeutic solutions for several diseases. The clinical use of either embryonic stem cells or induced pluripotent stem cells remains limited because of cell regulations, ethical considerations and the requirement for genetic manipulation, although these cells are theoretically highly beneficial. Adipose-derived stem cells (ASCs) appear to be an ideal population of stem cells for practical regenerative medicine, given that they are plentiful, of autologous tissue origin and thus non-immunogenic, and are more easily available because of minimal ethical considerations. Although ASCs originate from mesodermal lineages, recent preclinical studies have demonstrated that the use of ASCs in regenerative medicine is not limited to mesodermal tissue, but can also extend to both exodermal and endodermal tissues and organs. This review summarizes and discusses current preclinical and clinical data on the use of ASCs in regenerative medicine and discusses the future applications of such cell-based therapies.

  13. OEIS complex (omphalocele-exstrophy-imperforate anus-spinal defects): a review of 14 cases.

    Science.gov (United States)

    Keppler-Noreuil, K M

    2001-04-01

    OEIS complex refers to a combination of defects consisting of omphalocele, exstrophy of the cloaca, imperforate anus, and spinal defects. Possible embryologic mechanisms proposed for these findings have included: a single defect of early blastogenesis or a defect of mesodermal migration during the primitive streak period. Fourteen cases with OEIS complex and related malformations were reviewed for demographic features, prenatal and family histories, and clinical, radiological and pathological findings including the frequency and types of associated anomalies. The pathogenetic mechanisms causing OEIS complex and related malformations, such as anorectal and spinal defects, are discussed. The findings in these cases illustrate the spectrum of defects that can occur in the embryologic development of the cloaca and the urorectal septum. Differences in the timing and extent of mesenchymal ingrowth as well as cloacal membrane rupture may account for these variable findings. A developmental field defect involving the intraembryonic mesoderm suggests a possible etiologic role for homeobox genes, such as HLXB9 with mutations, resulting in anorectal and spine abnormalities, or retinoic acid receptors. OEIS complex with its mostly sporadic occurrence suggests etiologic heterogeneity with a possible role for environmental and genetic causes. Copyright 2001 Wiley-Liss, Inc.

  14. Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

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    Sophie R. Miller

    2017-03-01

    Full Text Available Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs, we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1 into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia.

  15. The Hectd1 Ubiquitin Ligase is Required for Development of the Head Mesenchyme and Neural Tube Closure

    Science.gov (United States)

    Zohn, Irene E.; Anderson, Kathryn V.; Niswander, Lee

    2009-01-01

    Closure of the cranial neural tube depends on normal development of the head mesenchyme. Homozygous-mutant embryos for the ENU-induced open mind (opm) mutation exhibit exencephaly associated with defects in head mesenchyme development and dorsal-lateral hinge point formation. The head mesenchyme in opm mutant embryos is denser than in wildtype embryos and displays an abnormal cellular organization. Since cells that originate from both the cephalic paraxial mesoderm and the neural crest populate the head mesenchyme, we explored the origin of the abnormal head mesenchyme. opm mutant embryos show apparently normal development of neural crest-derived structures. Furthermore, the abnormal head mesenchyme in opm mutant embryos is not derived from the neural crest, but instead expresses molecular markers of cephalic mesoderm. We also report the identification of the opm mutation in the ubiquitously expressed Hectd1 E3 ubiquitin ligase. Two different Hectd1 alleles cause incompletely penetrant neural tube defects in heterozygous animals, indicating that Hectd1 function is required at a critical threshold for neural tube closure. This low penetrance of neural tube defects in embryos heterozygous for Hectd1 mutations suggests that Hectd1 should be considered as candidate susceptibility gene in human neural tube defects. PMID:17442300

  16. Colonic mesenchyme differentiates into smooth muscle before its colonization by vagal enteric neural crest-derived cells in the chick embryo.

    Science.gov (United States)

    Bourret, Annick; Chauvet, Norbert; de Santa Barbara, Pascal; Faure, Sandrine

    2017-06-01

    During development, the gastrointestinal (GI) tract arises from a primary tube composed of mesoderm and endoderm. The mesoderm gives rise to the digestive mesenchyme, which in turn differentiates into multiple tissues, namely the submucosa, the interstitial cells of Cajal and the smooth muscle cells (SMCs). Concomitant with these early patterning events, the primitive GI tract is colonized by vagal enteric neural crest-derived cells (vENCDCs), a population of cells that gives rise to the enteric nervous system, the intrinsic innervation of the GI tract. Reciprocal neuro-mesenchymal interactions are essential for the coordinated development of GI musculature. The aim of this study is to examine and compare the kinetics of mesenchymal cell differentiation into SMCs along the anterior-posterior axis to the pattern of vENCDCs migration using whole-mount in situ hybridization and paraffin section immunofluorescence analyses on chick embryonic GI tracts from E4-Stage 23 to E7-Stages 30-31. We confirmed that gastric and pre-umbilical intestine mesenchyme differentiation into SMCs occurs after vENCDCs colonization. However, we found that colonic and post-umbilical intestine mesenchyme differentiation occurs before vENCDCs colonization. These findings suggest that regional-specific mechanisms are involved in the mesenchyme differentiation into SMCs along the GI anterior-posterior axis.

  17. Pathological axes of wound repair: Gastrulation revisited

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    Aller Maria-Angeles

    2010-09-01

    Full Text Available Abstract Post-traumatic inflammation is formed by molecular and cellular complex mechanisms whose final goal seems to be injured tissue regeneration. In the skin -an exterior organ of the body- mechanical or thermal injury induces the expression of different inflammatory phenotypes that resemble similar phenotypes expressed during embryo development. Particularly, molecular and cellular mechanisms involved in gastrulation return. This is a developmental phase that delineates the three embryonic germ layers: ectoderm, endoderm and mesoderm. Consequently, in the post-natal wounded skin, primitive functions related with the embryonic mesoderm, i.e. amniotic and yolk sac-derived, are expressed. Neurogenesis and hematogenesis stand out among the primitive function mechanisms involved. Interestingly, in these phases of the inflammatory response, whose molecular and cellular mechanisms are considered as traces of the early phases of the embryonic development, the mast cell, a cell that is supposedly inflammatory, plays a key role. The correlation that can be established between the embryonic and the inflammatory events suggests that the results obtained from the research regarding both great fields of knowledge must be interchangeable to obtain the maximum advantage.

  18. Identification of Cardiomyocyte-Fated Progenitors from Human-Induced Pluripotent Stem Cells Marked with CD82

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    Masafumi Takeda

    2018-01-01

    Full Text Available Summary: Here, we find that human-induced pluripotent stem cell (hiPSC-derived cardiomyocyte (CM-fated progenitors (CFPs that express a tetraspanin family glycoprotein, CD82, almost exclusively differentiate into CMs both in vitro and in vivo. CD82 is transiently expressed in late-stage mesoderm cells during hiPSC differentiation. Purified CD82+ cells gave rise to CMs under nonspecific in vitro culture conditions with serum, as well as in vivo after transplantation to the subrenal space or injured hearts in mice, indicating that CD82 successfully marks CFPs. CD82 overexpression in mesoderm cells as well as in undifferentiated hiPSCs increased the secretion of exosomes containing β-catenin and reduced nuclear β-catenin protein, suggesting that CD82 is involved in fated restriction to CMs through Wnt signaling inhibition. This study may contribute to the understanding of CM differentiation mechanisms and to cardiac regeneration strategies. : Takeda et al. find that CD82+ is a cell-surface marker on cardiomyocyte-fated progenitors made from human iPSCs. Keywords: iPSCs, CD82, cardiomyocytes, progenitors, exosome, Wnt inhibition

  19. 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.

  20. Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1.

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    Christopher Terranova

    Full Text Available Genetic studies have placed the Fgfr1 gene at the top of major ontogenic pathways that enable gastrulation, tissue development and organogenesis. Using genome-wide sequencing and loss and gain of function experiments the present investigation reveals a mechanism that underlies global and direct gene regulation by the nuclear form of FGFR1, ensuring that pluripotent Embryonic Stem Cells differentiate into Neuronal Cells in response to Retinoic Acid. Nuclear FGFR1, both alone and with its partner nuclear receptors RXR and Nur77, targets thousands of active genes and controls the expression of pluripotency, homeobox, neuronal and mesodermal genes. Nuclear FGFR1 targets genes in developmental pathways represented by Wnt/β-catenin, CREB, BMP, the cell cycle and cancer-related TP53 pathway, neuroectodermal and mesodermal programing networks, axonal growth and synaptic plasticity pathways. Nuclear FGFR1 targets the consensus sequences of transcription factors known to engage CREB-binding protein, a common coregulator of transcription and established binding partner of nuclear FGFR1. This investigation reveals the role of nuclear FGFR1 as a global genomic programmer of cell, neural and muscle development.

  1. History of Innate Immunity in Neurodegenerative Disorders

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    Patrick eMcGeer

    2011-12-01

    Full Text Available The foundations of innate immunity in neurodegenerative disorders were first laid by Hortega in 1919. He identified and named microglia, recognizing them as cells of mesodermal origin. Van Furth in 1969 elaborated the monocyte phagocytic system with microglia as the brain representatives. Validation of these concepts did not occur until 1987 when HLA-DR was identified on activated microglia in a spectrum of neurological disorders. HLA-DR had already been established as a definitive marker of immunocompetent cells of mesodermal origin. It was soon determined that the observed inflammatory reaction was an innate immune response. A rapid expansion of the field took place as other markers of an innate immune response were found that were made by neurons, astrocytes, oligodendroglia and endothelial cells. The molecules included complement proteins and their regulators, inflammatory cytokines, chemokines, acute phase reactants, prostaglandins, proteases, protease inhibitors, coagulation factors, fibrinolytic factors, anaphylotoxins, integrins, free radical generators, and other unidentified neurotoxins. The Nimmerjahn movies demonstrated that resting microglia were constantly active, sampling the surround and responding rapidly to brain damage. Ways of reducing the neurotoxic innate immune response and stimulating a healing response continue to be sought as a means for ameliorating the pathology in a spectrum of chronic degenerative disorders.

  2. The PDZ-GEF protein Dizzy regulates the establishment of adherens junctions required for ventral furrow formation in Drosophila.

    Science.gov (United States)

    Spahn, Philipp; Ott, Alice; Reuter, Rolf

    2012-08-15

    The PDZ-GEF protein Dizzy (Dzy) and its downstream GTPase Rap1 have pleiotropic roles during development of the Drosophila embryo. Here, we show that maternally provided Dzy and Rap1 first function during ventral furrow formation (VFF) where they are critical to guarantee rapid apical cell constrictions. Contraction of the apical actomyosin filament system occurs independently of Dzy and Rap1, but loss of Dzy results in a delayed establishment of the apical adherens junction (AJ) belt, whereas in the absence of Rap1 only a fragmentary apical AJ belt is formed in the epithelium. The timely establishment of apical AJs appears to be essential for coupling actomyosin contractions to cell shape change and to assure completion of the ventral furrow. Immediately after VFF, the downregulation of Dzy and Rap1 is necessary to allow normal mesodermal development to continue after the epithelial-to-mesenchymal transition, as overexpression of Dzy or of constitutively active Rap1 compromises mesodermal migration and monolayer formation. We propose that Dzy and Rap1 are crucial factors regulating the dynamics of AJs during gastrulation.

  3. Highly conserved functions of the Brachyury gene on morphogenetic movements: insight from the early-diverging phylum Ctenophora.

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    Yamada, Atsuko; Martindale, Mark Q; Fukui, Akimasa; Tochinai, Shin

    2010-03-01

    Brachyury, a member of the T-box transcription family identified in a diverse array of metazoans, was initially recognized for its function in mesoderm formation and notochord differentiation in vertebrates; however, its ancestral role has been suggested to be in control of morphogenetic movements. Here, we show that morpholino oligonucleotide knockdown of Brachyury (MlBra) in embryos of a ctenophore, one of the most ancient groups of animals, prevents the invagination of MlBra expressing stomodeal cells and is rescued with corresponding RNA injections. Injection of RNA encoding a dominant-interfering construct of MlBra causes identical phenotypes to that of RNA encoding a dominant-interfering form of Xenopus Brachyury (Xbra) in Xenopus embryos. Both injected embryos down-regulate Xbra downstream genes, Xbra itself and Xwnt11 but not axial mesodermal markers, resulting in failure to complete gastrulation due to loss of convergent extension movements. Moreover, animal cap assay reveals that MlBra induces Xwnt11 like Xbra. Overall results using Xenopus embryos show that these two genes are functionally interchangeable. These functional experiments demonstrate for the first time in a basal metazoan that the primitive role of Brachyury is to regulate morphogenetic movements, rather than to specify endomesodermal fates, and the role is conserved between non-bilaterian metazoans and vertebrates. Copyright 2009 Elsevier Inc. All rights reserved.

  4. Skeletal Muscle Cell Induction from Pluripotent Stem Cells

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    Yusaku Kodaka

    2017-01-01

    Full Text Available Embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs have the potential to differentiate into various types of cells including skeletal muscle cells. The approach of converting ESCs/iPSCs into skeletal muscle cells offers hope for patients afflicted with the skeletal muscle diseases such as the Duchenne muscular dystrophy (DMD. Patient-derived iPSCs are an especially ideal cell source to obtain an unlimited number of myogenic cells that escape immune rejection after engraftment. Currently, there are several approaches to induce differentiation of ESCs and iPSCs to skeletal muscle. A key to the generation of skeletal muscle cells from ESCs/iPSCs is the mimicking of embryonic mesodermal induction followed by myogenic induction. Thus, current approaches of skeletal muscle cell induction of ESCs/iPSCs utilize techniques including overexpression of myogenic transcription factors such as MyoD or Pax3, using small molecules to induce mesodermal cells followed by myogenic progenitor cells, and utilizing epigenetic myogenic memory existing in muscle cell-derived iPSCs. This review summarizes the current methods used in myogenic differentiation and highlights areas of recent improvement.

  5. A spinal cord fate map in the avian embryo: while regressing, Hensen's node lays down the notochord and floor plate thus joining the spinal cord lateral walls.

    Science.gov (United States)

    Catala, M; Teillet, M A; De Robertis, E M; Le Douarin, M L

    1996-09-01

    The spinal cord of thoracic, lumbar and caudal levels is derived from a region designated as the sinus rhomboidalis in the 6-somite-stage embryo. Using quail/chick grafts performed in ovo, we show the following. (1) The floor plate and notochord derive from a common population of cells, located in Hensen's node, which is equivalent to the chordoneural hinge (CNH) as it was defined at the tail bud stage. (2) The lateral walls and the roof of the neural tube originate caudally and laterally to Hensen's node, during the regression of which the basal plate anlage is bisected by floor plate tissue. (3) Primary and secondary neurulations involve similar morphogenetic movements but, in contrast to primary neurulation, extensive bilateral cell mixing is observed on the dorsal side of the region of secondary neurulation. (4) The posterior midline of the sinus rhomboidalis gives rise to somitic mesoderm and not to spinal cord. Moreover, mesodermal progenitors are spatially arranged along the rest of the primitive streak, more caudal cells giving rise to more lateral embryonic structures. Together with the results reported in our study of tail bud development (Catala, M., Teillet, M.-A. and Le Douarin, N.M. (1995). Mech. Dev. 51, 51-65), these results show that the mechanisms that preside at axial elongation from the 6-somite stage onwards are fundamentally similar during the complete process of neurulation.

  6. Patterning and gastrulation defects caused by the tw18 lethal are due to loss of Ppp2r1a

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    Lisette Lange

    2017-06-01

    Full Text Available The mouse t haplotype, a variant 20 cM genomic region on Chromosome 17, harbors 16 embryonic control genes identified by recessive lethal mutations isolated from wild mouse populations. Due to technical constraints so far only one of these, the tw5 lethal, has been cloned and molecularly characterized. Here we report the molecular isolation of the tw18 lethal. Embryos carrying the tw18 lethal die from major gastrulation defects commencing with primitive streak formation at E6.5. We have used transcriptome and marker gene analyses to describe the molecular etiology of the tw18 phenotype. We show that both WNT and Nodal signal transduction are impaired in the mutant epiblast, causing embryonic patterning defects and failure of primitive streak and mesoderm formation. By using a candidate gene approach, gene knockout by homologous recombination and genetic rescue, we have identified the gene causing the tw18 phenotype as Ppp2r1a, encoding the PP2A scaffolding subunit PR65alpha. Our work highlights the importance of phosphatase 2A in embryonic patterning, primitive streak formation, gastrulation, and mesoderm formation downstream of WNT and Nodal signaling.

  7. CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis.

    Science.gov (United States)

    Ounzain, Samir; Micheletti, Rudi; Arnan, Carme; Plaisance, Isabelle; Cecchi, Dario; Schroen, Blanche; Reverter, Ferran; Alexanian, Michael; Gonzales, Christine; Ng, Shi Yan; Bussotti, Giovanni; Pezzuto, Iole; Notredame, Cedric; Heymans, Stephane; Guigó, Roderic; Johnson, Rory; Pedrazzini, Thierry

    2015-12-01

    Long noncoding RNAs (lncRNAs) are emerging as important regulators of developmental pathways. However, their roles in human cardiac precursor cell (CPC) remain unexplored. To characterize the long noncoding transcriptome during human CPC cardiac differentiation, we profiled the lncRNA transcriptome in CPCs isolated from the human fetal heart and identified 570 lncRNAs that were modulated during cardiac differentiation. Many of these were associated with active cardiac enhancer and super enhancers (SE) with their expression being correlated with proximal cardiac genes. One of the most upregulated lncRNAs was a SE-associated lncRNA that was named CARMEN, (CAR)diac (M)esoderm (E)nhancer-associated (N)oncoding RNA. CARMEN exhibits RNA-dependent enhancing activity and is upstream of the cardiac mesoderm-specifying gene regulatory network. Interestingly, CARMEN interacts with SUZ12 and EZH2, two components of the polycomb repressive complex 2 (PRC2). We demonstrate that CARMEN knockdown inhibits cardiac specification and differentiation in cardiac precursor cells independently of MIR-143 and -145 expression, two microRNAs located proximal to the enhancer sequences. Importantly, CARMEN expression was activated during pathological remodeling in the mouse and human hearts, and was necessary for maintaining cardiac identity in differentiated cardiomyocytes. This study demonstrates therefore that CARMEN is a crucial regulator of cardiac cell differentiation and homeostasis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Contribution of hedgehog signaling to the establishment of left-right asymmetry in the sea urchin.

    Science.gov (United States)

    Warner, Jacob F; Miranda, Esther L; McClay, David R

    2016-03-15

    Most bilaterians exhibit a left-right asymmetric distribution of their internal organs. The sea urchin larva is notable in this regard since most adult structures are generated from left sided embryonic structures. The gene regulatory network governing this larval asymmetry is still a work in progress but involves several conserved signaling pathways including Nodal, and BMP. Here we provide a comprehensive analysis of Hedgehog signaling and it's contribution to left-right asymmetry. We report that Hh signaling plays a conserved role to regulate late asymmetric expression of Nodal and that this regulation occurs after Nodal breaks left-right symmetry in the mesoderm. Thus, while Hh functions to maintain late Nodal expression, the molecular asymmetry of the future coelomic pouches is locked in. Furthermore we report that cilia play a role only insofar as to transduce Hh signaling and do not have an independent effect on the asymmetry of the mesoderm. From this, we are able to construct a more complete regulatory network governing the establishment of left-right asymmetry in the sea urchin. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Spatial expression of Hox cluster genes in the ontogeny of a sea urchin

    Science.gov (United States)

    Arenas-Mena, C.; Cameron, A. R.; Davidson, E. H.

    2000-01-01

    The Hox cluster of the sea urchin Strongylocentrous purpuratus contains ten genes in a 500 kb span of the genome. Only two of these genes are expressed during embryogenesis, while all of eight genes tested are expressed during development of the adult body plan in the larval stage. We report the spatial expression during larval development of the five 'posterior' genes of the cluster: SpHox7, SpHox8, SpHox9/10, SpHox11/13a and SpHox11/13b. The five genes exhibit a dynamic, largely mesodermal program of expression. Only SpHox7 displays extensive expression within the pentameral rudiment itself. A spatially sequential and colinear arrangement of expression domains is found in the somatocoels, the paired posterior mesodermal structures that will become the adult perivisceral coeloms. No such sequential expression pattern is observed in endodermal, epidermal or neural tissues of either the larva or the presumptive juvenile sea urchin. The spatial expression patterns of the Hox genes illuminate the evolutionary process by which the pentameral echinoderm body plan emerged from a bilateral ancestor.

  10. Characterization and mutant analysis of the Drosophila sema 5c gene.

    Science.gov (United States)

    Bahri, S M; Chia, W; Yang, X

    2001-07-01

    Class V semaphorins are transmembrane glycoproteins characterised by the presence of thrombospondin type I (Tsp) repeats linked to their extracellular semaphorin domain. Sema 5C is the only class V semaphorin found in Drosophila. Dsema 5C RNA is maternally provided and its embryonic expression is prominent in the mesoderm and muscle attachment sites. Here, we show that DSema 5C exists in two protein isoforms as a result of alternative splicing and that both protein and RNA have similar expression patterns. Using a combination of various molecular markers, we show that the DSema 5C protein becomes enriched in mesodermal cells that would normally give rise to fat body and visceral structures. In late embryos, DSema 5C is expressed in segment boundary cells that would constitute subsets of muscle attachment sites. Both RNA and protein are excluded from the somatic precursors and the mature muscles. The expression data suggest DSema 5C localised to the epidermal component of muscle attachment sites. Mutations in Dsema 5C were isolated from a P-element excision screen and by blotting analysis. The Dsema 5C mutants are homozygous viable and show no obvious embryonic phenotypes, suggesting that the maternal and zygotic components of Dsema 5C are not essential for fly development. Copyright 2001 Wiley-Liss, Inc.

  11. In Vivo Regulation of the Zebrafish Endoderm Progenitor Niche by T-Box Transcription Factors

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    Andrew C. Nelson

    2017-06-01

    Full Text Available T-box transcription factors T/Brachyury homolog A (Ta and Tbx16 are essential for correct mesoderm development in zebrafish. The downstream transcriptional networks guiding their functional activities are poorly understood. Additionally, important contributions elsewhere are likely masked due to redundancy. Here, we exploit functional genomic strategies to identify Ta and Tbx16 targets in early embryogenesis. Surprisingly, we discovered they not only activate mesodermal gene expression but also redundantly regulate key endodermal determinants, leading to substantial loss of endoderm in double mutants. To further explore the gene regulatory networks (GRNs governing endoderm formation, we identified targets of Ta/Tbx16-regulated homeodomain transcription factor Mixl1, which is absolutely required in zebrafish for endoderm formation. Interestingly, we find many endodermal determinants coordinately regulated through common genomic occupancy by Mixl1, Eomesa, Smad2, Nanog, Mxtx2, and Pou5f3. Collectively, these findings augment the endoderm GRN and reveal a panel of target genes underlying the Ta, Tbx16, and Mixl1 mutant phenotypes.

  12. Expression and functional study of extracellular BMP antagonists during the morphogenesis of the digits and their associated connective tissues.

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    Carlos I Lorda-Diez

    Full Text Available The purpose of this study is to gain insight into the role of BMP signaling in the diversification of the embryonic limb mesodermal progenitors destined to form cartilage, joints, and tendons. Given the importance of extracellular BMP modulators in in vivo systems, we performed a systematic search of those expressed in the developing autopod during the formation of the digits. Here, we monitored the expression of extracellular BMP modulators including: Noggin, Chordin, Chordin-like 1, Chordin-like 2, Twisted gastrulation, Dan, BMPER, Sost, Sostdc1, Follistatin, Follistatin-like 1, Follistatin-like 5 and Tolloid. These factors show differential expression domains in cartilage, joints and tendons. Furthermore, they are induced in specific temporal patterns during the formation of an ectopic extra digit, preceding the appearance of changes that are identifiable by conventional histology. The analysis of gene regulation, cell proliferation and cell death that are induced by these factors in high density cultures of digit progenitors provides evidence of functional specialization in the control of mesodermal differentiation but not in cell proliferation or apoptosis. We further show that the expression of these factors is differentially controlled by the distinct signaling pathways acting in the developing limb at the stages covered by this study. In addition, our results provide evidence suggesting that TWISTED GASTRULATION cooperates with CHORDINS, BMPER, and NOGGIN in the establishment of tendons or cartilage in a fashion that is dependent on the presence or absence of TOLLOID.

  13. Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes.

    Science.gov (United States)

    Nasrallah, Rabab; Fast, Eva M; Solaimani, Parham; Knezevic, Kathy; Eliades, Alexia; Patel, Rahima; Thambyrajah, Roshana; Unnikrishnan, Ashwin; Thoms, Julie; Beck, Dominik; Vink, Chris S; Smith, Aileen; Wong, Jason; Shepherd, Mairi; Kent, David; Roychoudhuri, Rahul; Paul, Fabian; Klippert, Julia; Hammes, Annette; Willnow, Thomas; Göttgens, Bertie; Dzierzak, Elaine; Zon, Leonard I; Lacaud, George; Kouskoff, Valerie; Pimanda, John E

    2016-10-13

    Enhancers are the primary determinants of cell identity, and specific promoter/enhancer combinations of Endoglin (ENG) have been shown to target blood and endothelium in the embryo. Here, we generated a series of embryonic stem cell lines, each targeted with reporter constructs driven by specific promoter/enhancer combinations of ENG, to evaluate their discriminative potential and value as molecular probes of the corresponding transcriptome. The Eng promoter (P) in combination with the -8/+7/+9-kb enhancers, targeted cells in FLK1 mesoderm that were enriched for blast colony forming potential, whereas the P/-8-kb enhancer targeted TIE2+/c-KIT+/CD41- endothelial cells that were enriched for hematopoietic potential. These fractions were isolated using reporter expression and their transcriptomes profiled by RNA-seq. There was high concordance between our signatures and those from embryos with defects at corresponding stages of hematopoiesis. Of the 6 genes that were upregulated in both hemogenic mesoderm and hemogenic endothelial fractions targeted by the reporters, LRP2, a multiligand receptor, was the only gene that had not previously been associated with hematopoiesis. We show that LRP2 is indeed involved in definitive hematopoiesis and by doing so validate the use of reporter gene-coupled enhancers as probes to gain insights into transcriptional changes that facilitate cell fate transitions. © 2016 by The American Society of Hematology.

  14. Periodic repression of Notch pathway genes governs the segmentation of Xenopus embryos.

    Science.gov (United States)

    Jen, W C; Gawantka, V; Pollet, N; Niehrs, C; Kintner, C

    1999-06-01

    During the development of the vertebrate embryo, genes encoding components of the Notch signaling pathway are required for subdividing the paraxial mesoderm into repeating segmental structures, called somites. These genes are thought to act in the presomitic mesoderm when cells form prospective somites, called somitomeres, but their exact function remains unknown. To address this issue, we have identified two novel genes, called ESR-4 and ESR-5, which are transcriptionally activated in the somitomeres of Xenopus embryos by the Su(H)-dependent Notch signaling pathway. We show that the expression of these genes divides each somitomere into an anterior and posterior half, and that this pattern of expression is generated by a mechanism that actively represses the expression of the Notch pathway genes when paraxial cells enter a critical region and form a somitomere. Repression of Notch signaling during somitomere formation requires a negative feedback loop and inhibiting the activity of genes in this loop has a profound effect on somitomere size. Finally we present evidence that once somitomeres form, ESR-5 mediates a positive feedback loop, which maintains the expression of Notch pathway genes. We propose a model in which Notch signaling plays a key role in both establishing and maintaining segmental identity during somitomere formation in Xenopus embryos.

  15. A new insight into the histogenesis of 'mesodermomas'--malignant mesotheliomas.

    Science.gov (United States)

    Donna, A; Betta, P G; Bianchi, V; Ribotta, M; Bellingeri, D; Robutti, F; Marchesini, A

    1991-09-01

    A myogenic phenotype was induced in cultures of human mesothelial cells treated for 72 h with atrazine, a triazine derivative. Immunoreactivity for both myosin and myoglobin was detected in a large number of these cells, irrespective of their polygonal or spindle morphology, whereas no expression of desmin was observed. These findings support the embryological identity of mesothelium and mesoderm, the former being, in the post-embryonic stage, potentially capable of differentiation along the same lineages which the latter normally displays during embryogenesis. In the light of this concept it can be assumed that primary malignancies arising from the mesothelium have the competence to express the pluripotent nature of embryonic mesoderm, and hence the term mesodermoma is appropriate for this group of tumours, including mesotheliomas in a classical sense. A postulated mechanism for the phenotypic change of mesothelial cells is also outlined, involving atrazine conversion to 5-aza-chloro-cytidine, a probable DNA hypomethylating and gene activating agent, like its analogue 5-azacytidine.

  16. Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1).

    Science.gov (United States)

    Terranova, Christopher; Narla, Sridhar T; Lee, Yu-Wei; Bard, Jonathan; Parikh, Abhirath; Stachowiak, Ewa K; Tzanakakis, Emmanuel S; Buck, Michael J; Birkaya, Barbara; Stachowiak, Michal K

    2015-01-01

    Genetic studies have placed the Fgfr1 gene at the top of major ontogenic pathways that enable gastrulation, tissue development and organogenesis. Using genome-wide sequencing and loss and gain of function experiments the present investigation reveals a mechanism that underlies global and direct gene regulation by the nuclear form of FGFR1, ensuring that pluripotent Embryonic Stem Cells differentiate into Neuronal Cells in response to Retinoic Acid. Nuclear FGFR1, both alone and with its partner nuclear receptors RXR and Nur77, targets thousands of active genes and controls the expression of pluripotency, homeobox, neuronal and mesodermal genes. Nuclear FGFR1 targets genes in developmental pathways represented by Wnt/β-catenin, CREB, BMP, the cell cycle and cancer-related TP53 pathway, neuroectodermal and mesodermal programing networks, axonal growth and synaptic plasticity pathways. Nuclear FGFR1 targets the consensus sequences of transcription factors known to engage CREB-binding protein, a common coregulator of transcription and established binding partner of nuclear FGFR1. This investigation reveals the role of nuclear FGFR1 as a global genomic programmer of cell, neural and muscle development.

  17. Clonal analysis identifies hemogenic endothelium as the source of the blood-endothelial common lineage in the mouse embryo.

    Science.gov (United States)

    Padrón-Barthe, Laura; Temiño, Susana; Villa del Campo, Cristina; Carramolino, Laura; Isern, Joan; Torres, Miguel

    2014-10-16

    The first blood and endothelial cells of amniote embryos appear in close association in the blood islands of the yolk sac (YS). This association and in vitro lineage analyses have suggested a common origin from mesodermal precursors called hemangioblasts, specified in the primitive streak during gastrulation. Fate mapping and chimera studies, however, failed to provide strong evidence for a common origin in the early mouse YS. Additional in vitro studies suggest instead that mesodermal precursors first generate hemogenic endothelium, which then generate blood cells in a linear sequence. We conducted an in vivo clonal analysis to determine the potential of individual cells in the mouse epiblast, primitive streak, and early YS. We found that early YS blood and endothelial lineages mostly derive from independent epiblast populations, specified before gastrulation. Additionally, a subpopulation of the YS endothelium has hemogenic activity and displays characteristics similar to those found later in the embryonic hemogenic endothelium. Our results show that the earliest blood and endothelial cell populations in the mouse embryo are specified independently, and that hemogenic endothelium first appears in the YS and produces blood precursors with markers related to definitive hematopoiesis. © 2014 by The American Society of Hematology.

  18. The Pleural Mesothelium in Development and Disease

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    Hitesh eBatra

    2014-08-01

    Full Text Available The pleural mesothelium, derived from the embryonic mesoderm, is formed by a metabolically active monolayer of cells that blanket the chest wall and lungs on the parietal and visceral surfaces, respectively. The pleura and lungs are formed as a result of an intricate relationship between the mesoderm and the endoderm during development. Pleural Mesothelial Cells (PMCs are known to express Wilms tumor-1 (Wt1 gene and in lineage labeling studies of the developing embryo, PMCs were found to track into the lung parenchyma and undergo mesothelial-mesenchymal transition (MMT to form α-smooth muscle actin (α-SMA-positive cells of the mesenchyme and vasculature. There is definite evidence that mesothelial cells can differentiate and this seems to play an important role in pleural and parenchymal pathologies. Mesothelial cells can differentiate into adipocytes, chondrocytes and osteoblasts; and have been shown to clonally generate fibroblasts and smooth muscle cells in murine models. This supports the possibility that they may also modulate lung injury-repair by re-activation of developmental programs in the adult reflecting an altered recapitulation of development, with implications for regenerative biology of the lung.

  19. Building the Vertebrate Spine

    Science.gov (United States)

    Pourquié, Olivier

    2008-03-01

    The vertebrate body can be subdivided along the antero-posterior (AP) axis into repeated structures called segments. This periodic pattern is established during embryogenesis by the somitogenesis process. Somites are generated in a rhythmic fashion from the paraxial mesoderm and subsequently differentiate to give rise to the vertebrae and skeletal muscles of the body. Somite formation involves an oscillator-the segmentation clock-whose periodic signal is converted into the periodic array of somite boundaries. This clock drives the dynamic expression of cyclic genes in the presomitic mesoderm and requires Notch and Wnt signaling. Microarray studies of the mouse presomitic mesoderm transcriptome reveal that the segmentation clock drives the periodic expression of a large network of cyclic genes involved in cell signaling. Mutually exclusive activation of the Notch/FGF and Wnt pathways during each cycle suggests that coordinated regulation of these three pathways underlies the clock oscillator. In humans, mutations in the genes associated to the function of this oscillator such as Dll3 or Lunatic Fringe result in abnormal segmentation of the vertebral column such as those seen in congenital scoliosis. Whereas the segmentation clock is thought to set the pace of vertebrate segmentation, the translation of this pulsation into the reiterated arrangement of segment boundaries along the AP axis involves dynamic gradients of FGF and Wnt signaling. The FGF signaling gradient is established based on an unusual mechanism involving mRNA decay which provides an efficient means to couple the spatio-temporal activation of segmentation to the posterior elongation of the embryo. Another striking aspect of somite production is the strict bilateral symmetry of the process. Retinoic acid was shown to control aspects of this coordination by buffering destabilizing effects from the embryonic left-right machinery. Defects in this embryonic program controlling vertebral symmetry might lead

  20. Increased cardiogenesis in P19-GFP teratocarcinoma cells expressing the propeptide IGF-1Ea

    Energy Technology Data Exchange (ETDEWEB)

    Poudel, Bhawana [Heart Science Centre, National Heart and Lung Institute, Imperial College, London (United Kingdom); Bilbao, Daniel [EMBL, Mouse Biology Unit, Monterotondo (Italy); Sarathchandra, Padmini; Germack, Renee [Heart Science Centre, National Heart and Lung Institute, Imperial College, London (United Kingdom); Rosenthal, Nadia [Heart Science Centre, National Heart and Lung Institute, Imperial College, London (United Kingdom); Australian Regenerative Medicine Institute, Monash University, Melbourne (Australia); Santini, Maria Paola, E-mail: m.santini@imperial.ac.uk [Heart Science Centre, National Heart and Lung Institute, Imperial College, London (United Kingdom)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer In this study, we explored the function of IGF-1Ea propeptide in inducing cardiogenesis of stem cells. Black-Right-Pointing-Pointer IGF-1Ea promoted cardiac mesodermal induction in uncommitted cells. Black-Right-Pointing-Pointer Under differentiation condition, IGF-1Ea increased expression of cardiac differentiation markers. Black-Right-Pointing-Pointer Furthermore, it promoted formation of finely organized sarcomeric structure. Black-Right-Pointing-Pointer IGF-1Ea propeptide may be a good candidate to improve production of cardiomyocytes from pluripotent cells. -- Abstract: The mechanism implicated in differentiation of endogenous cardiac stem cells into cardiomyocytes to regenerate the heart tissue upon an insult remains elusive, limiting the therapeutical goals to exogenous cell injection and/or gene therapy. We have shown previously that cardiac specific overexpression of the insulin-like growth factor 1 propeptide IGF-1Ea induces beneficial myocardial repair after infarct. Although the mechanism is still under investigation, the possibility that this propeptide may be involved in promoting stem cell differentiation into the cardiac lineage has yet to be explored. To investigate whether IGF-1Ea promote cardiogenesis, we initially modified P19 embryonal carcinoma cells to express IGF-1Ea. Taking advantage of their cardiomyogenic nature, we analyzed whether overexpression of this propeptide affected cardiac differentiation program. The data herein presented showed for the first time that constitutively overexpressed IGF-1Ea increased cardiogenic differentiation program in both undifferentiated and DMSO-differentiated cells. In details, IGF-1Ea overexpression promoted localization of alpha-actinin in finely organized sarcomeric structure compared to control cells and upregulated the cardiac mesodermal marker NKX-2.5 and the ventricular structural protein MLC2v. Furthermore, activated IGF-1 signaling promoted cardiac

  1. Carcinosarcoma of the Rectum: Report of a Rare Colorectal Malignancy and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Alexis Sudlow

    2015-01-01

    Full Text Available Carcinosarcoma (CS is a rare mixed mesodermal malignancy most commonly affecting the female reproductive organs, respiratory tract, head, and neck. Though infrequent, it may affect the gastrointestinal tract, most often the oesophagus and only very rarely the rectum. Histologically, it is composed of two distinct elements of epithelial and mesenchymal origin. Clinically, it is a very aggressive tumour with many patients presenting with metastatic lymph nodes or distant metastases at the time of diagnosis. Prognosis is poor despite intervention with the majority of patients dying within six months. Due to the rarity of this condition, there are no specific treatment guidelines presently available. We describe the case of an 80-year-old patient with carcinosarcoma of the rectum with discussion of the immunohistochemistry and review the available literature pertaining to this rare presentation.

  2. Hair defects in Hoxc13 mutant mice.

    Science.gov (United States)

    Godwin, A R; Capecchi, M R

    1999-12-01

    Hox genes encode transcription factors that are important during normal embryonic development of diverse organisms including vertebrates. In mammals, Hox genes are responsible for conferring regional identity in embryonic tissues, including the limb bud, the neural tube, the presomitic mesoderm and the intestinal tract. Recent studies have demonstrated expression of Hox genes in skin and hair follicles, suggesting potential functions for these genes in epidermal appendages. These studies are reviewed here with emphasis on Hoxc13, as Hoxc13 mutants are the first Hox mutants to demonstrate overt hair defects. In addition, because Hoxc13 does not show regionally restricted expression in the skin, as demonstrated for other Hox genes, the potentially different roles of Hoxc13 versus other Hox genes in the skin are discussed.

  3. Isl1 expression at the venous pole identifies a novel role for the second heart field in cardiac development.

    Science.gov (United States)

    Snarr, Brian S; O'Neal, Jessica L; Chintalapudi, Mastan R; Wirrig, Elaine E; Phelps, Aimee L; Kubalak, Steven W; Wessels, Andy

    2007-11-09

    The right ventricle and outflow tract of the developing heart are derived from mesodermal progenitor cells from the second heart field (SHF). SHF cells have been characterized by expression of the transcription factor Islet-1 (Isl1). Although Isl1 expression has also been reported in the venous pole, the specific contribution of the SHF to this part of the heart is unknown. Here we show that Isl1 is strongly expressed in the dorsal mesenchymal protrusion (DMP), a non-endocardially-derived mesenchymal structure involved in atrioventricular septation. We further demonstrate that abnormal development of the SHF-derived DMP is associated with the pathogenesis of atrioventricular septal defects. These results identify a novel role for the SHF.

  4. A late requirement for Wnt and FGF signalling during activin-induced formation of foregut endoderm from mouse embryonic stem cells

    DEFF Research Database (Denmark)

    Hansson, Mattias; Petersen, Dorthe Rønn; Peterslund, Janny M.L.

    2009-01-01

    Here we examine how BMP, Wnt, and FGF signaling modulate activin-induced mesendodermal differentiation of mouse ES cells grown under defined conditions in adherent monoculture. We monitor ES cells containing reporter genes for markers of primitive streak (PS) and its progeny and extend previous...... is found at the lowest activin concentration. The expression of Gsc and other anterior markers induced by activin is prevented by treatment with BMP4, which induces T expression and subsequent mesodermal development. We show that canonical Wnt signaling is required only during late stages of activin....... Notably, activin induction of Gsc-GFP(+) cells appears refractory to inhibition of canonical Wnt signaling but shows a dependence on early as well as late FGF signaling. Additionally, we find a late dependence on FGF signaling during induction of Sox17(+) cells by activin while BMP4-induced T expression...

  5. Roentgenographic features of neurofibromatosis von Recklinghausen

    International Nuclear Information System (INIS)

    Galanski, M.; Vogelsang, H.; Cramer, B.M.; Thun, F.; Peters, P.E.

    1983-01-01

    The basic abnormality of neurofibromatosis consists not only of a maldevelopment of the neuroectoderm but also of the mesoderm. Therefore any organ or system of the body may be involved. Following a short clinical review of the central (acoustic) and peripheral type the well known and the more unusual radiographic findings are summarized. They include cranial and intracranial manifestations (orbitosphenoid dysplasia, bone defects of the skull, acoustic neuroma, glioma of the optic nerve and chiasm, meningioma), spinal lesions (scoliosis, vetebral scalloping, meningocele, neuroma, ependymoma), skeletal abnormalities (pseudarthrosis), cardiovascular manifestations, pulmonary fibrosis, tumors of the gastrointestinal and urinary tract and different endocrinopathies. Some of the roentgeologic symptoms are very characteristic and allow definitive diagnosis. (orig.)

  6. Fibroepithelial polyps causing ureteropelvic junction obstruction in a child.

    Science.gov (United States)

    Li, Wei-Ming; Wu, Wen-Jeng; Ke, Hung-Lung; Chai, Chee-Yin; Chou, Yii-Her; Huang, Chun-Hsiung

    2005-06-01

    Fibroepithelial polyps of the ureter are benign tumors arising from mesodermal tissue in the ureter wall. They are extremely rare lesions that can cause ureteropelvic junction obstruction in children. In this report, we describe an 11-year-old boy with fibroepithelial polyps of the ureter that caused left ureteropelvic junction obstruction. He presented with a 6-month history of left abdominal and flank pain. He also had short stature. Intravenous pyelography showed hydronephrosis without filling defects at the left ureteropelvic junction. Exploration revealed several finger-like polyps obstructing the lumen. This area was resected segmentally and a dismembered pyeloplasty was performed. No complications occurred during the postoperative period. The boy caught up in growth after the operation. Fibroepithelial polyps were confirmed by histology.

  7. Fibroepithelial Polyps Causing Ureteropelvic Junction Obstruction in a Child

    Directory of Open Access Journals (Sweden)

    Wei-Ming Li

    2005-06-01

    Full Text Available Fibroepithelial polyps of the ureter are benign tumors arising from mesodermal tissue in the ureter wall. They are extremely rare lesions that can cause ureteropelvic junction obstruction in children. In this report, we describe an 11-year-old boy with fibroepithelial polyps of the ureter that caused left ureteropelvic junction obstruction. He presented with a 6-month history of left abdominal and flank pain. He also had short stature. Intravenous pyelography showed hydronephrosis without filling defects at the left ureteropelvic junction. Exploration revealed several finger-like polyps obstructing the lumen. This area was resected segmentally and a dismembered pyeloplasty was performed. No complications occurred during the postoperative period. The boy caught up in growth after the operation. Fibroepithelial polyps were confirmed by histology.

  8. [Bilateral ureteral polyps in children: a case report].

    Science.gov (United States)

    Sun, Peng-hao; Na, Wan-li; Nan, Yong-hao; Tian, Wen-jie; Liu, Ming

    2012-08-18

    Fibroepithelial polyp of the ureter is a benign tumor of mesodermal origin that rarely occurs in children. The most common presenting symptoms are hematuria and flank pain by obstruction of the urinary tract. The etiology of this tumor is still not clear. It occurs more frequently in boys and often arises in the proximal ureter and the ureteropelvic junction. The preoperative diagnosis is difficult. We present here the case of a 11-year-old boy who had fibroepithelial polyps as the cause of the left flank ureteropelvic junction obstruction at pyeloplasty, and had the same condition on the right flank 5 years ago. We used polypectomy and pyeloureterostomy to treat the boy. No major intraoperative or preoperative complications developed.

  9. Left-Right Asymmetrical Development of the Proepicardium

    Directory of Open Access Journals (Sweden)

    Jan Schlueter

    2013-07-01

    Full Text Available The proepicardium (PE is a cluster of cells that forms on the cardiac inflow tract and gives rise to the epicardium and connective tissue and largely contributes to the coronary vasculature. In many vertebrates, the PE undergoes left-right asymmetrical development. While PE cells and marker genes can be initially found on both sides, only the right-sided PE will fully develop and ultimately deliver cells to the heart. Several signalling inputs, like FGF and BMP signals, are involved in PE induction in the lateral plate mesoderm, as well as during inflow tract formation and, also, control asymmetric PE development. These signalling events will be put into the context of embryonic left-right asymmetry determination. Finally, it will be discussed whether PE development may serve as a readout for asymmetric inflow tract morphogenesis.

  10. A Glutamine-Rich Factor Affects Stem Cell Genesis in Leech

    Directory of Open Access Journals (Sweden)

    Kristi A. Hohenstein

    2010-01-01

    Full Text Available Leech embryogenesis is a model for investigating cellular and molecular processes of development. Due to the unusually large size of embryonic stem cells (teloblasts: 50–300 μm in the glossiphoniid leech, Theromyzon tessulatum, and the presence of identifiable stem cell precursors (proteloblasts, we previously isolated a group of genes upregulated upon stem cell birth. In the current study, we show that one of these genes, designated Theromyzon proliferation (Tpr, is required for normal stem cell genesis; specifically, transient Tpr knockdown experiments conducted with antisense oligonucleotides and monitored by semiquantitative RT-PCR, caused abnormal proteloblast proliferation leading to embryonic death, but did not overtly affect neuroectodermal or mesodermal stem cell development once these cells were born. Tpr encodes a large glutamine-rich (∼34% domain that shares compositional similarity with strong transcriptional enhancers many of which have been linked with trinucleotide repeat disorders (e.g., Huntington's.

  11. Craniofacial development and the evolution of the vertebrates: the old problems on a new background.

    Science.gov (United States)

    Kuratani, Shigeru

    2005-01-01

    Based on recent advances in experimental embryology and molecular genetics, the morphogenetic program for the vertebrate cranium is summarized and several unanswered classical problems are reviewed. In particular, the presence of mesodermal segmentation in the head, the homology of the trabecular cartilage, and the origin of the dermal skull roof are discussed. The discovery of the neural-crest-derived ectomesenchyme and the roles of the homeobox genes have allowed the classical concept of head segmentation unchanged since Goethe to be re-interpreted in terms of developmental mechanisms at the molecular and cellular levels. In the context of evolutionary developmental biology, the importance of generative constraints is stressed as the developmental factor that generates the homologous morphological patterns apparent in various groups of vertebrates. Furthermore, a modern version of the germ-layer theory is defined in terms of the conserved differentiation of cell lineages, which is again questioned from the vantage of evolutionary developmental biology.

  12. A new heart for a new head in vertebrate cardiopharyngeal evolution.

    Science.gov (United States)

    Diogo, Rui; Kelly, Robert G; Christiaen, Lionel; Levine, Michael; Ziermann, Janine M; Molnar, Julia L; Noden, Drew M; Tzahor, Eldad

    2015-04-23

    It has been more than 30 years since the publication of the new head hypothesis, which proposed that the vertebrate head is an evolutionary novelty resulting from the emergence of neural crest and cranial placodes. Neural crest generates the skull and associated connective tissues, whereas placodes produce sensory organs. However, neither crest nor placodes produce head muscles, which are a crucial component of the complex vertebrate head. We discuss emerging evidence for a surprising link between the evolution of head muscles and chambered hearts - both systems arise from a common pool of mesoderm progenitor cells within the cardiopharyngeal field of vertebrate embryos. We consider the origin of this field in non-vertebrate chordates and its evolution in vertebrates.

  13. Mapping Human Pluripotent-to-Cardiomyocyte Differentiation: Methylomes, Transcriptomes, and Exon DNA Methylation “Memories”

    Directory of Open Access Journals (Sweden)

    Joshua D. Tompkins

    2016-02-01

    Full Text Available The directed differentiation of human cardiomyocytes (CMs from pluripotent cells provides an invaluable model for understanding mechanisms of cell fate determination and offers considerable promise in cardiac regenerative medicine. Here, we utilize a human embryonic stem cell suspension bank, produced according to a good manufacturing practice, to generate CMs using a fully defined and small molecule-based differentiation strategy. Primitive and cardiac mesoderm purification was used to remove non-committing and multi-lineage populations and this significantly aided the identification of key transcription factors, lncRNAs, and essential signaling pathways that define cardiomyogenesis. Global methylation profiles reflect CM development and we report on CM exon DNA methylation “memories” persisting beyond transcription repression and marking the expression history of numerous developmentally regulated genes, especially transcription factors.

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

    Science.gov (United States)

    Nie, Xuguang; Wang, Qin; Jiao, Kai

    2014-01-01

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

  15. Snail regulates p21WAF/CIP1 expression in cooperation with E2 A and Twist

    International Nuclear Information System (INIS)

    Takahashi, Eishi; Funato, Noriko; Higashihori, Norihisa; Hata, Yuiro; Gridley, Thomas; Nakamura, Masataka

    2004-01-01

    Snail, a zinc-finger transcriptional repressor, is essential for mesoderm and neural crest cell formation and epithelial-mesenchymal transition. The basic helix-loop-helix transcription factors E2A and Twist have been linked with Snail during embryonic development. In this study, we examined the role of Snail in cellular differentiation through regulation of p21 WAF/CIP1 expression. A reporter assay with the p21 promoter demonstrated that Snail inhibited expression of p21 induced by E2A. Co-expression of Snail with Twist showed additive inhibitory effects. Deletion mutants of the p21 promoter revealed that sequences between -270 and -264, which formed a complex with unidentified nuclear factor(s), were critical for E2A and Snail function. The E2A-dependent expression of the endogenous p21 gene was also inhibited by Snail

  16. Stem cells in the embryonic kidney.

    Science.gov (United States)

    Nishinakamura, R

    2008-04-01

    The mammalian kidney, the metanephros, is formed by a reciprocally inductive interaction between two precursor tissues, the metanephric mesenchyme and the ureteric bud. The ureteric bud induces the metanephric mesenchyme to differentiate into the epithelia of glomeruli and renal tubules. Multipotent renal progenitors that form colonies upon Wnt4 stimulation and strongly express Sall1 exist in the metanephric mesenchyme; these cells can partially reconstitute a three-dimensional structure in an organ culture setting. Six2 maintains this mesenchymal progenitor population by opposing Wnt4-mediated epithelialization. Upon epithelial tube formation, Notch2 is required for the differentiation of proximal nephron structures (podocyte and proximal tubules). In addition, the induction methods of the intermediate mesoderm, the precursor of the metanephric mesenchyme, begin to be elucidated. If derivation of metanephric mesenchyme becomes possible, we will be closer to the generation and manipulation of multiple cell lineages in the kidney.

  17. Intractable Diseases Treated with Intra-Bone Marrow-Bone Marrow Transplantation

    Directory of Open Access Journals (Sweden)

    Ming eLi

    2014-09-01

    Full Text Available Bone marrow transplantation (BMT is used to treat hematological disorders, autoimmune diseases and lymphoid cancers. Intra bone marrow-BMT (IBM-BMT has been proven to be a powerful strategy for allogeneic BMT due to the rapid hematopoietic recovery and the complete restoration of T cell functions. IBM-BMT not only replaces hematopoietic stem cells but also mesenchymal stem cells (MSMCs. MSMCs are multi-potent stem cells that can be isolated from bone marrow, umbilical cord blood, and adipose tissue. MSMCs play an important role in the support of hematopoiesis, and modify and influence the innate and adaptive immune systems. MSMCs also differentiate into mesodermal, endodermal and ectodermal lineage cells to repair tissues. This review aims to summarize the functions of bone marrow-derived- MSMCs, and the treatment of intractable diseases such as rheumatoid arthritis and malignant tumors with IBM-BMT.

  18. Trichobezoar in Vagina: Assessment for Child Sexual Abuse and Diagnostic Result of Forensic Science.

    Science.gov (United States)

    Bağ, Özlem; Acar, Buğra Han; Öztürk, Şenol; Alşen, Sevay; Ecevit, Çiğdem

    2017-03-01

    Vaginal discharge and bleeding in children require a through and thoughtful evaluation to diagnose the underlying problem including infections, sexual abuse, and vaginal foreign bodies. We report a 6-year-old girl presenting with bloody vaginal discharge, carefully evaluated for sexual abuse, and finally diagnosed as a vaginal foreign body after vaginoscopy. A rolling hair ball was extracted from the vagina and was diagnosed as trichobezoar pathologically without any endo-ecto-mesodermal residual tissue. The hair ball was genetically detected and diagnosed to belong herself by containing no foreign structure. Child sexual abuse was ruled out by forensic interview at CAC and report of forensic science that reported genetic structure belonging to the child. Medicolegal assessment helped in final diagnosis to exclude child sexual abuse. © 2016 American Academy of Forensic Sciences.

  19. An abbreviated protocol for multilineage neural differentiation of murine embryonic stem cells and its perturbation by methyl mercury.

    Science.gov (United States)

    Theunissen, P T; Schulpen, S H W; van Dartel, D A M; Hermsen, S A B; van Schooten, F J; Piersma, A H

    2010-07-01

    Alternative assays are highly desirable to reduce the extensive experimental animal use in developmental toxicity testing. In the present study, we developed an improved test system for assessing neurodevelopmental toxicity using differentiating embryonic stem cells. We advanced previously established methods by merging, modifying and abbreviating the original 20-day protocol into a more efficient 13-day neural differentiation protocol. Using morphological observation, immunocytochemistry, gene expression and flow cytometry, it was shown predominantly multiple lineages of neuroectodermal cells were formed in our protocol and to a lower extent, endodermal and mesodermal differentiated cell types. This abbreviated protocol should lead to an advanced screening method using morphology in combination with selected differentiation markers aimed at predicting neurodevelopmental toxicity. Finally, the assay was shown to express differential sensitivity to a model developmental neurotoxicant, methyl mercury.

  20. Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-beta/Activin/Nodal signaling using SB-431542

    DEFF Research Database (Denmark)

    Mahmood, Amer; Harkness, Linda; Schrøder, Henrik Daa

    2010-01-01

    Directing differentiation of human embryonic stem cells (hESC) into specific cell types using an easy and reproducible protocol is a prerequisite for the clinical use of hESC in regenerative medicine procedures. Here, we report a protocol for directing the differentiation of hESC into mesenchymal...... in vivo. Interestingly, SB-OG cells cultured in 10% fetal bovine serum (FBS) developed into a homogeneous population of mesenchymal progenitors that expressed CD markers characteristic of mesenchymal stem cells (MSC): CD44(+) (100%), CD73(+) (98%), CD146(+) (96%) and CD166(+) (88%) with the ability...... progenitor cells. We demonstrate that inhibition of TGF-beta/Activin/Nodal signaling during embryoid bodies (EB) formation using SB-431542 (SB) in serum free medium, markedly up-regulated paraxial mesodermal markers (TBX6, TBX5), and several myogenic developmental markers including early myogenic...

  1. hESC Differentiation toward an Autonomic Neuronal Cell Fate Depends on Distinct Cues from the Co-Patterning Vasculature

    Directory of Open Access Journals (Sweden)

    Lisette M. Acevedo

    2015-06-01

    Full Text Available To gain insight into the cellular and molecular cues that promote neurovascular co-patterning at the earliest stages of human embryogenesis, we developed a human embryonic stem cell model to mimic the developing epiblast. Contact of ectoderm-derived neural cells with mesoderm-derived vasculature is initiated via the neural crest (NC, not the neural tube (NT. Neurovascular co-patterning then ensues with specification of NC toward an autonomic fate requiring vascular endothelial cell (EC-secreted nitric oxide (NO and direct contact with vascular smooth muscle cells (VSMCs via T-cadherin-mediated homotypic interactions. Once a neurovascular template has been established, NT-derived central neurons then align themselves with the vasculature. Our findings reveal that, in early human development, the autonomic nervous system forms in response to distinct molecular cues from VSMCs and ECs, providing a model for how other developing lineages might coordinate their co-patterning.

  2. The CMV early enhancer/chicken beta actin (CAG) promoter can be used to drive transgene expression during the differentiation of murine embryonic stem cells into vascular progenitors

    DEFF Research Database (Denmark)

    Alexopoulou, Annika N; Couchman, John R; Whiteford, James

    2008-01-01

    BACKGROUND: Mouse embryonic stem cells cultured in vitro have the ability to differentiate into cells of the three germ layers as well as germ cells. The differentiation mimics early developmental events, including vasculogenesis and early angiogenesis and several differentiation systems are being...... used to identify factors that are important during the formation of the vascular system. Embryonic stem cells are difficult to transfect, while downregulation of promoter activity upon selection of stable transfectants has been reported, rendering the study of proteins by overexpression difficult....... RESULTS: CCE mouse embryonic stem cells were differentiated on collagen type IV for 4-5 days, Flk1+ mesodermal cells were sorted and replated either on collagen type IV in the presence of VEGFA to give rise to endothelial cells and smooth muscle cells or in collagen type I gels for the formation...

  3. Mesenchymal cells reactivate Snail1 expression to drive three-dimensional invasion programs

    DEFF Research Database (Denmark)

    Rowe, R.G.; Li, X.Y.; Hu, Y.

    2009-01-01

    Epithelial-mesenchymal transition (EMT) is required for mesodermal differentiation during development. The zinc-finger transcription factor, Snail1, can trigger EMT and is sufficient to transcriptionally reprogram epithelial cells toward a mesenchymal phenotype during neoplasia and fibrosis....... Whether Snail1 also regulates the behavior of terminally differentiated mesenchymal cells remains unexplored. Using a Snai1 conditional knockout model, we now identify Snail1 as a regulator of normal mesenchymal cell function. Snail1 expression in normal fibroblasts can be induced by agonists known...... to promote proliferation and invasion in vivo. When challenged within a tissue-like, three-dimensional extracellular matrix, Snail1-deficient fibroblasts exhibit global alterations in gene expression, which include defects in membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invasive activity...

  4. Cloning of fragments of novel homeobox genes expressed during regeneration in planarians

    Energy Technology Data Exchange (ETDEWEB)

    Lukyanov, K.A.; Tarabykin, V.S.; Potapov, V.K. [and others

    1994-11-01

    The polymerase chain reaction with degenerate primers corresponding to the most conservative amino acids 16-21 (ELEKEF) and 49-54 (WPQNRR) of the Antennapedia class homeodomains was used for the amplification of cDNA from regenerating planarians (asexual race of Dugesia tigrina). A total of six new Antennapedia-like homeobox sequences, designated Dutarh-1-Dutarh-6 (Dugesia tigrina asexual race homeobox gene), have been identified. Their comparison with other homeobox genes using a Genebee software (the EMBL Data Library) showed that all sequences except Dutarh-6 belong to the Antennapedia class. Dutarh-6 is closely related to a recently described novel homeobox gene subfamily which includes mouse mesodermal homeobox genes Max-1 and Max-2 and rat homeobox gene Gax. 17 refs., 2 figs.

  5. Management of Klippel-Trenauny syndrome with multiple organ involvement

    Directory of Open Access Journals (Sweden)

    Nassiri Javad

    2007-01-01

    Full Text Available Klippel-Trenauny syndrome is a disturbance in the development of the mesodermal and ectodermal tissues occurring in utero, which is characterized by vascular nevi, varicose veins, soft tissue, and occasionally, bone hyperplasia. Our patient is a 6-year-old boy with presentation of left lower extremity over growth, abdominal mass, abdominal pain, bilateral buttock mass, rectal bleeding, and skin hemangiomatosis. The major problems of this case were involvement of the levator ani, external anal sphincter, and encasement of the sciatic nerves within the buttock mass. We concluded that the use of muscle and nerve stimulator for detection and saving sphincters and the nerves in these cases could improve the results of surgical resection.

  6. Expression of the metastasis-associated mts1 gene during mouse development

    DEFF Research Database (Denmark)

    Klingelhöfer, Jörg; Ambartsumian, N S; Lukanidin, E M

    1997-01-01

    motility. In order to understand the function of this gene, we studied the expression of the mts1 mRNA and protein in vivo during mouse development. Both mRNA and protein were present in high concentrations from 12.5 to 18.5 days post coitum (dpc) in a variety of developing embryonic tissue of mesodermal...... differentiation and morphogenesis of mesenchymal tissues such as the mesenchyme surrounding the tips of digits, the mesenchyme underlying the epithelium of the bladder, and the mesenchyme between the primordia of the nasal capsule and the skin as well as in the developing dermal papilla of hair and tooth follicle....... In developing bone, Mts1 was expressed in invasive mesenchymal cells and in osteoclasts. The results presented here suggest that Mtsl plays an important role in mouse development during differentiation and function of macrophages and might be involved in different processes associated with mesenchymal...

  7. Isolation of autologous adipose tissue-derived mesenchymal stem cells for bone repair.

    Science.gov (United States)

    Raposio, E; Bonomini, S; Calderazzi, F

    2016-11-01

    Adipose tissue represents an abundant and accessible source of adult stem cells that can differentiate into cells and tissues of mesodermal origin, including osteogenic cells. This paper describes the procedure to obtain a 5-cm 3 saline sample, containing the adipose-derived stem cells (ASCs) pellet, starting from lipoaspirate obtained from a conventional abdominal liposuction. A mean of 2.5×10 6  cells is isolated for each procedure; 35% (875000) of these are CD34+/CD45- cells, which express a subset of both positive (CD10, CD13, CD44, CD59, CD73, CD90, HLAABC) and negative (CD33, CD39, CD102, CD106, CD146, HLADR) cell-associated surface antigens, characterizing them as ASCs. This procedure is easy, effective, economic and safe. It allows the harvesting of a significant number of ASCs that are ready for one-step bony regenerative surgical procedures. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. A solitary fibrous tumor of the retroperitoneum: CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Min; Kim, Chong Soo; Lee, Dong Keun; Cho, Baek Hwan [Chonbuk National Univ. College of Medicine, Chunju (Korea, Republic of); Han, Hyun Young [Euljy Mecical School, Seoul (Korea, Republic of)

    1999-01-01

    The solitary fibrous tumor is a rare spindle cell neoplasm of mesodermal origin. It usually arises in the pleura, though has recently been reported in the peritoneum and at nonserosal sites ; it is, however, extremely rare in the retroperitonum. The authors describe one case of a solitary fibrous tumor that occurred as a huge complex mass in the retroperitoneum of an adult. Preenhanced CT scans showed that the mass was sharply delineated from surrounding organs and that tumor density was the same as that of surrounding musculature. Peripheral Calcifications were noted, and postenhanced scans showed intense, gradual enhancement of solid portions of the mass, with nonenhanced cystic portions. Although not specific, solitary fibrous tumors must be included in the differential diagnosis of a large retroperitoneal tumor of complex consistency and with internal calcification.

  9. Two case reports of an unusual association between Klippel-Feil syndrome and amyotrophic lateral sclerosis: Do they share same genetic defect?

    Directory of Open Access Journals (Sweden)

    Koneru Lakshmi Umamaheshwar

    2013-01-01

    Full Text Available Klippel-Feil syndrome (KFS is an unusual skeletal disorder characterized by congenital fusion of two or more cervical vertebrae which can be sporadic or familial. KFS emerges to be a failure of the normal segmentation and fusion of the mesodermal somites during 3 rd and 8 th weeks of embryonic development. The triad of low posterior hairline, short neck, and restricted neck motion is present only in 50% and often associated with scoliosis, spina bifida, Sprengel′s deformity, cervical ribs, deafness, cleft palate, renal anomalies, congenital heart defects, and so on because of heterogeneous nature of the disease. The significance of KFS lies in the secondary effects produced on the nervous system, which usually presents with features of progressive cord and brain stem compression with relatively minor trauma. We here report two cases of KFS presented in association with amyotrophic lateral sclerosis. Only two such cases have been described in the literature in 1954 and 1975.

  10. Core issues in craniofacial myogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, Robert G., E-mail: kelly@ibdml.univ-mrs.fr [Developmental Biology Institute of Marseilles-Luminy, UMR6216 CNRS Universite de la Mediterranee, Campus de Luminy Case 907, 13288 Marseille Cedex 9 France (France)

    2010-11-01

    Branchiomeric craniofacial muscles control feeding, breathing and facial expression. These muscles differ on multiple counts from all other skeletal muscles and originate in a progenitor cell population in pharyngeal mesoderm characterized by a common genetic program with an adjacent population of cardiac progenitor cells, the second heart field, that gives rise to much of the heart. The transcription factors and signaling molecules that trigger the myogenic program at sites of branchiomeric muscle formation are correspondingly distinct from those in somite-derived muscle progenitor cells. Here new insights into the regulatory hierarchies controlling branchiomeric myogenesis are discussed. Differences in embryological origin are reflected in the lineage, transcriptional program and proliferative and differentiation properties of branchiomeric muscle satellite cells. These recent findings have important implications for our understanding of the diverse myogenic strategies operative both in the embryo and adult and are of direct biomedical relevance to deciphering the mechanisms underlying the cause and progression of muscle restricted myopathies.

  11. Ellis-van Creveld Syndrome: A Rare Clinical Report of Oral Rehabilitation by Interdisciplinary Approach

    Directory of Open Access Journals (Sweden)

    Talib Amin Naqash

    2018-01-01

    Full Text Available Ellis-van Creveld syndrome (EVC is a very rare genetic disorder that affects various tissues of ectodermal and mesodermal origin; patients with EVC present with typical oral deficiencies. The affected individuals are quite young at the time of oral evaluation. It is, therefore, important that these individuals are diagnosed and receive dental treatment at an early age for their physiologic and psychosocial well-being. Albeit there are numerous articles penned on the EVC, the treatise from an oral perspective is inadequate, covering only oral exhibitions and the preventive treatments. This article reviews the literature and serves as the first disquisition for oral rehabilitation of an EVC patient utilizing surgical, orthodontic, restorative, and prosthodontic management.

  12. Direct Genesis of Functional Rodent and Human Schwann Cells from Skin Mesenchymal Precursors

    Directory of Open Access Journals (Sweden)

    Matthew P. Krause

    2014-07-01

    Full Text Available Recent reports of directed reprogramming have raised questions about the stability of cell lineages. Here, we have addressed this issue, focusing upon skin-derived precursors (SKPs, a dermally derived precursor cell. We show by lineage tracing that murine SKPs from dorsal skin originate from mesenchymal and not neural crest-derived cells. These mesenchymally derived SKPs can, without genetic manipulation, generate functional Schwann cells, a neural crest cell type, and are highly similar at the transcriptional level to Schwann cells isolated from the peripheral nerve. This is not a mouse-specific phenomenon, since human SKPs that are highly similar at the transcriptome level can be made from neural crest-derived facial and mesodermally derived foreskin dermis and the foreskin SKPs can make myelinating Schwann cells. Thus, nonneural crest-derived mesenchymal precursors can differentiate into bona fide peripheral glia in the absence of genetic manipulation, suggesting that developmentally defined lineage boundaries are more flexible than widely thought.

  13. Central cemento-ossifying fibroma of posterior maxilla

    Directory of Open Access Journals (Sweden)

    Uday Shankar Yaga

    2015-01-01

    Full Text Available Cemento-ossifying fibromas (COFs are relatively rare, benign lesions affecting the jaws and other craniofacial bones and are included in the group of mesodermal odontogenic tumors by Gorlin. They have a predilection for females between the third and fourth decades of life, and about 60% of the lesions are seen most often in the mandibular arch, predominantly occurring in the premolar/molar region of the mandible. This report describes a case of central COF in a 49-year-old male involving the maxillary posterior region. The current case is reported because of the rarity of such lesions and the paucity of information concerning them in the dental literature. We believe that this case illustrates many of the clinical, radiographic, and histologic features associated with cemento-ossifying tumors.

  14. Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro.

    Science.gov (United States)

    Harrison, Sarah Ellys; Sozen, Berna; Christodoulou, Neophytos; Kyprianou, Christos; Zernicka-Goetz, Magdalena

    2017-04-14

    Mammalian embryogenesis requires intricate interactions between embryonic and extraembryonic tissues to orchestrate and coordinate morphogenesis with changes in developmental potential. Here, we combined mouse embryonic stem cells (ESCs) and extraembryonic trophoblast stem cells (TSCs) in a three-dimensional scaffold to generate structures whose morphogenesis is markedly similar to that of natural embryos. By using genetically modified stem cells and specific inhibitors, we show that embryogenesis of ESC- and TSC-derived embryos-ETS-embryos-depends on cross-talk involving Nodal signaling. When ETS-embryos develop, they spontaneously initiate expression of mesoderm and primordial germ cell markers asymmetrically on the embryonic and extraembryonic border, in response to Wnt and BMP signaling. Our study demonstrates the ability of distinct stem cell types to self-assemble in vitro to generate embryos whose morphogenesis, architecture, and constituent cell types resemble those of natural embryos. Copyright © 2017, American Association for the Advancement of Science.

  15. Perinatal features of omphalocele-exstrophy-imperforate anus-spinal defects (OEIS complex) associated with large meningomyeloceles and severe limb defects.

    Science.gov (United States)

    Chen, C P; Shih, S L; Liu, F F; Jan, S W; Jeng, C J; Lan, C C

    1997-05-01

    Omphalocele-Exstrophy-Imperforate anus-Spinal defects (OEIS complex), a combination of omphalocele, exstrophy of the bladder, an imperforate anus and spinal defects, arises from a single localized defect in the early development of the mesoderm that will later contribute to infraumbilical mesenchyme, cloacal septum, and caudal vertebrae. In this report, we document the perinatal features of two cases of OEIS complex associated with meningomyeloceles and severe lower limb defects, and discuss the prenatal diagnosis, inheritance, and differential diagnosis of this association of malformations. Although long-term survival can be achieved by successful corrective surgery, the associated structural defects such as large meningomyelocele and severe limb aplasia or hypoplasia, as seen in our patient, can influence the patient's quality of life. We would like to emphasize that an accurate prenatal diagnosis of OEIS complex and associated malformations is important for the detailed counseling of the family as well as appropriate perinatal management by the obstetricians, pediatric surgeons, urologists, neurosurgeons, and neonatologists.

  16. IFPA Senior Award Lecture

    DEFF Research Database (Denmark)

    Carter, A M

    2016-01-01

    BACKGROUND: Fetal membrane development varies greatly across mammals with significant implications for models of human placentation. METHOD: Therefore the major patterns of fetal membrane development are reviewed with special focus on functions of the inverted yolk sac in murine rodents. FINDINGS......: In most mammals, yolk sac and chorion form a choriovitelline placenta to support the early embryo, although this soon is supplanted by a chorioallantoic placenta. Human and haplorrhine primates follow a second pattern where precocious development of the extraembryonic mesoderm leads to formation...... of a secondary yolk sac within the exocoelom. In rodents there is an inverted visceral yolk sac that encloses the embryo and amnion and functions as an accessory to the chorioallantoic placenta through term. Where present, the inverted yolk sac performs a number of functions that in human are assumed...

  17. Bone Marrow-Derived Mesenchymal Cell Differentiation toward Myogenic Lineages: Facts and Perspectives

    Directory of Open Access Journals (Sweden)

    Daniela Galli

    2014-01-01

    Full Text Available Bone marrow-derived mesenchymal stem cells (BM-MSCs are valuable platforms for new therapies based on regenerative medicine. BM-MSCs era is coming of age since the potential of these cells is increasingly demonstrated. In fact, these cells give origin to osteoblasts, chondroblasts, and adipocyte precursors in vitro, and they can also differentiate versus other mesodermal cell types like skeletal muscle precursors and cardiomyocytes. In our short review, we focus on the more recent manipulations of BM-MSCs toward skeletal and heart muscle differentiation, a growing field of obvious relevance considering the toll of muscle disease (i.e., muscular dystrophies, the heavier toll of heart disease in developed countries, and the still not completely understood mechanisms of muscle differentiation and repair.

  18. Somitogenesis: From somite to skeletal muscle.

    Science.gov (United States)

    Musumeci, Giuseppe; Castrogiovanni, Paola; Coleman, Raymond; Szychlinska, Marta Anna; Salvatorelli, Lucia; Parenti, Rosalba; Magro, Gaetano; Imbesi, Rosa

    2015-01-01

    Myogenesis is controlled by an elaborate system of extrinsic and intrinsic regulatory mechanisms in all development stages. The aim of this review is to provide an overview of the different stages of myogenesis and muscle differentiation in mammals, starting from somitogenesis and analysis of the different portions that constitute the mature somite. Particular attention was paid to regulatory genes, in addition to mesodermal stem cells, which represent the earliest elements of myogenesis. Finally, the crucial role of growth factors, molecules of vital importance in contractile regulation, hormones and their function in skeletal muscle differentiation, growth and metabolism, and the role played by central nervous system, are discussed. Copyright © 2015 Elsevier GmbH. All rights reserved.

  19. Sturge Weber Syndrome

    Directory of Open Access Journals (Sweden)

    Kazi Nilufar Moly

    2016-07-01

    Full Text Available Sturge weber syndrome is a rare sporadic condition of mesodermal phacomatosis, also called encephalotrigeminal angio­matosis (synonyms : fourth phacomatosis or mother spot, is a neurocutaneous disorder with angiomas that involve the leptomeninges (leptomeningeal angiomas and the skin of the face (purple colored flat cutaneous haemangiomas , typically in the ophthalmic (V1 and maxillary (V2 distributions of the trigeminal nerve. The hallmark of sturge weber syndrome is a facial cutaneous venous dilation, also referred to as a nevus flammeus or port wine stain (PWS. Because of the rarity, we report here a one & half year old male child who presented with features of the Sturge Weber Syndrome on both side of face.

  20. Human fetal cardiac progenitors: The role of stem cells and progenitors in the fetal and adult heart.

    Science.gov (United States)

    Bulatovic, Ivana; Månsson-Broberg, Agneta; Sylvén, Christer; Grinnemo, Karl-Henrik

    2016-02-01

    The human fetal heart is formed early during embryogenesis as a result of cell migrations, differentiation, and formative blood flow. It begins to beat around gestation day 22. Progenitor cells are derived from mesoderm (endocardium and myocardium), proepicardium (epicardium and coronary vessels), and neural crest (heart valves, outflow tract septation, and parasympathetic innervation). A variety of molecular disturbances in the factors regulating the specification and differentiation of these cells can cause congenital heart disease. This review explores the contribution of different cardiac progenitors to the embryonic heart development; the pathways and transcription factors guiding their expansion, migration, and functional differentiation; and the endogenous regenerative capacity of the adult heart including the plasticity of cardiomyocytes. Unfolding these mechanisms will become the basis for understanding the dynamics of specific congenital heart disease as well as a means to develop therapy for fetal as well as postnatal cardiac defects and heart failure. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Making headway: the roles of Hox genes and neural crest cells in craniofacial development.

    Science.gov (United States)

    Trainor, Paul A

    2003-04-14

    Craniofacial development is an extraordinarily complex process requiring the orchestrated integration of multiple specialized tissues such as the surface ectoderm, neural crest, mesoderm, and pharyngeal endoderm in order to generate the central and peripheral nervous systems, axial skeleton, musculature, and connective tissues of the head and face. How do the characteristic facial structures develop in the appropriate locations with their correct shapes and sizes, given the widely divergent patterns of cell movements that occur during head development? The patterning information could depend upon localized interactions between the epithelial and mesenchymal tissues or alternatively, the developmental program for the characteristic facial structures could be intrinsic to each individual tissue precursor. Understanding the mechanisms that control vertebrate head development is an important issue since craniofacial anomalies constitute nearly one third of all human congenital defects. This review discusses recent advances in our understanding of neural crest cell patterning and the dynamic nature of the tissue interactions that are required for normal craniofacial development.

  2. Induction of skeletal abnormalities and autophagy in Paracentrotus lividus sea urchin embryos exposed to gadolinium.

    Science.gov (United States)

    Martino, Chiara; Chiarelli, Roberto; Bosco, Liana; Roccheri, Maria Carmela

    2017-09-01

    Gadolinium (Gd) concentration is constantly increasing in the aquatic environment, becoming an emergent environmental pollutant. We investigated the effects of Gd on Paracentrotus lividus sea urchin embryos, focusing on skeletogenesis and autophagy. We observed a delay of biomineral deposition at 24 hours post fertilization (hpf), and a strong impairment of skeleton growth at 48 hpf, frequently displayed by an asymmetrical pattern. Skeleton growth was found partially resumed in recovery experiments. The mesodermal cells designated to biomineralization were found correctly migrated at 24 hpf, but not at 48 hpf. Western blot analysis showed an increase of the LC3-II autophagic marker at 24 and 48 hpf. Confocal microscopy studies confirmed the increased number of autophagolysosomes and autophagosomes. Results show the hazard of Gd in the marine environment, indicating that Gd is able to affect different aspects of sea urchin development: morphogenesis, biomineralization, and stress response through autophagy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Sclerites in different tissues of Mediterranean Echinodermata.

    Science.gov (United States)

    Ocaña Martín, Amelia; Tierno de Figueroa, J Manuel; Palomino-Morales, Rogelio J

    2006-06-01

    The presence of sclerites in different mesodermal tissues was studied in thirteen species of Mediterranean echinoderms representing the five living classes. In the species of Asteroidea and Crinoidea examined, sclerites were present only in specific tissues. In the species of Ophiuroidea and, especially, Echinoidea and Holothuroidea examined, sclerites were present in almost every tissue, but with considerable variation among species and tissues. Data on sclerite shape, size, and relative abundance (measured as tissue abundance) are presented. The data support the possible functional role of sclerites as reinforcing structures, as well as their possible use as taxonomic characters. Finally, the need of more studies to elucidate the ontogenetic and phylogenetic implications of sclerites is discussed.

  4. Expression of biomarker genes of differentiation in D3 mouse embryonic stem cells after exposure to different embryotoxicant and non-embryotoxicant model chemicals

    Directory of Open Access Journals (Sweden)

    Andrea C. Romero

    2015-12-01

    Full Text Available There is a necessity to develop in vitro methods for testing embryotoxicity (Romero et al., 2015 [1]. We studied the progress of D3 mouse embryonic stem cells differentiation exposed to model embryotoxicants and non-embryotoxicants chemicals through the expression of biomarker genes. We studied a set of 16 different genes biomarkers of general cellular processes (Cdk1, Myc, Jun, Mixl, Cer and Wnt3, ectoderm formation (Nrcam, Nes, Shh and Pnpla6, mesoderm formation (Mesp1, Vegfa, Myo1e and Hdac7 and endoderm formation (Flk1 and Afp. We offer dose response in order to derive the concentration causing either 50% or 200% of expression of the biomarker gene. These records revealed to be a valuable end-point to predict in vitro the embryotoxicity of chemicals (Romero et al., 2015 [1].

  5. Mapping Human Pluripotent-to-Cardiomyocyte Differentiation: Methylomes, Transcriptomes, and Exon DNA Methylation “Memories”

    Science.gov (United States)

    Tompkins, Joshua D.; Jung, Marc; Chen, Chang-yi; Lin, Ziguang; Ye, Jingjing; Godatha, Swetha; Lizhar, Elizabeth; Wu, Xiwei; Hsu, David; Couture, Larry A.; Riggs, Arthur D.

    2016-01-01

    The directed differentiation of human cardiomyocytes (CMs) from pluripotent cells provides an invaluable model for understanding mechanisms of cell fate determination and offers considerable promise in cardiac regenerative medicine. Here, we utilize a human embryonic stem cell suspension bank, produced according to a good manufacturing practice, to generate CMs using a fully defined and small molecule-based differentiation strategy. Primitive and cardiac mesoderm purification was used to remove non-committing and multi-lineage populations and this significantly aided the identification of key transcription factors, lncRNAs, and essential signaling pathways that define cardiomyogenesis. Global methylation profiles reflect CM development and we report on CM exon DNA methylation “memories” persisting beyond transcription repression and marking the expression history of numerous developmentally regulated genes, especially transcription factors. PMID:26981572

  6. Mapping Human Pluripotent-to-Cardiomyocyte Differentiation: Methylomes, Transcriptomes, and Exon DNA Methylation "Memories".

    Science.gov (United States)

    Tompkins, Joshua D; Jung, Marc; Chen, Chang-Yi; Lin, Ziguang; Ye, Jingjing; Godatha, Swetha; Lizhar, Elizabeth; Wu, Xiwei; Hsu, David; Couture, Larry A; Riggs, Arthur D

    2016-02-01

    The directed differentiation of human cardiomyocytes (CMs) from pluripotent cells provides an invaluable model for understanding mechanisms of cell fate determination and offers considerable promise in cardiac regenerative medicine. Here, we utilize a human embryonic stem cell suspension bank, produced according to a good manufacturing practice, to generate CMs using a fully defined and small molecule-based differentiation strategy. Primitive and cardiac mesoderm purification was used to remove non-committing and multi-lineage populations and this significantly aided the identification of key transcription factors, lncRNAs, and essential signaling pathways that define cardiomyogenesis. Global methylation profiles reflect CM development and we report on CM exon DNA methylation "memories" persisting beyond transcription repression and marking the expression history of numerous developmentally regulated genes, especially transcription factors.

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

    Science.gov (United States)

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

    2017-11-01

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

  8. Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock

    Science.gov (United States)

    Bessho, Yasumasa; Hirata, Hiromi; Masamizu, Yoshito; Kageyama, Ryoichiro

    2003-01-01

    Hes7, a bHLH gene essential for somitogenesis, displays cyclic expression of mRNA in the presomitic mesoderm (PSM). Here, we show that Hes7 protein is also expressed in a dynamic manner, which depends on proteasome-mediated degradation. Spatial comparison revealed that Hes7 and Lunatic fringe (Lfng) transcription occurs in the Hes7 protein-negative domains. Furthermore, Hes7 and Lfng transcription is constitutively up-regulated in the absence of Hes7 protein and down-regulated by stabilization of Hes7 protein. Thus, periodic repression by Hes7 protein is critical for the cyclic transcription of Hes7 and Lfng, and this negative feedback represents a molecular basis for the segmentation clock. PMID:12783854

  9. Functions and Mechanisms of Fibroblast Growth Factor (FGF Signalling in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Hans-Arno J. Müller

    2013-03-01

    Full Text Available Intercellular signalling via growth factors plays an important role in controlling cell differentiation and cell movements during the development of multicellular animals. Fibroblast Growth Factor (FGF signalling induces changes in cellular behaviour allowing cells in the embryo to move, to survive, to divide or to differentiate. Several examples argue that FGF signalling is used in multi-step morphogenetic processes to achieve and maintain a transitional state of the cells required for the control of cell fate. In the genetic model Drosophila melanogaster, FGF signalling via the receptor tyrosine kinases Heartless (Htl and Breathless (Btl is particularly well studied. These FGF receptors affect gene expression, cell shape and cell–cell interactions during mesoderm layer formation, caudal visceral muscle (CVM formation, tracheal morphogenesis and glia differentiation. Here, we will address the current knowledge of the biological functions of FGF signalling in the fly on the tissue, at a cellular and molecular level.

  10. Clinico-pathological studies of CSF dissemination of glioblastoma and medulloblastoma

    International Nuclear Information System (INIS)

    Kato, Kyozo; Yoshida, Jun; Kageyama, Naoki

    1986-01-01

    Clinico-pathological findings of CSF dissemination which was diagnosed on CT scan, were studied on 13 cases of glioblastoma and 9 cases of medulloblastoma. The type of CSF dissemination and the prognosis of patients were both different between glioblastoma and medulloblastoma. In the former, the dissemination was predominantly in ventricular walls and in the latter, in basal cisterns. The mean survival time after the diagnosis of dissemination is 6 months of glioblastoma as compared with 13 months of medulloblastoma. The Pathological studies show that subependymal and/or subpial infiltration of tumor cells, and thickness of arachnoid membrane by marked mesodermal reaction were demonstrated in cases of glioblastoma. On the contrary, tumor cells of medulloblastoma grow markedly in the subarachnoid space and/or on the ependymal layers. From these pathological findings of CSF dissemination, it will be resulted that the prognosis of glioblastoma is much more poor that of medulloblastoma. (author)

  11. Comparative myoanatomy of cycliophoran life cycle stages

    DEFF Research Database (Denmark)

    Neves, Ricardo C.; Cunha, Maria R.; Funch, Peter

    2010-01-01

    The metazoan phylum Cycliophora includes small cryptic epibionts that live attached to the mouthparts of clawed lobsters. The life cycle is complex, with alternating sexual and asexual generations, and involves several sessile and free-living stages. So far, the morphological and genetic...... on the dorsal side, whereas on the ventral side, longitudinal muscles and a V-shaped muscle structure are present. These muscles are complemented by additional dorsoventral muscles. The mesodermal muscle fibers attach to the cuticle via the epidermis in all life cycle stages studied herein. The musculature...... of the female is similar to that of the Pandora larva of Symbion americanus and includes dorsoventral muscles and longitudinal muscles that run in the dorsal and ventral body region. Overall, our results reveal striking similarities in the muscular arrangement of the life cycle stages of both Symbion species. J...

  12. The forces that shape embryos: physical aspects of convergent extension by cell intercalation

    International Nuclear Information System (INIS)

    Keller, Ray; Shook, David; Skoglund, Paul

    2008-01-01

    We discuss the physical aspects of the morphogenic process of convergence (narrowing) and extension (lengthening) of tissues by cell intercalation. These movements, often referred to as 'convergent extension', occur in both epithelial and mesenchymal tissues during embryogenesis and organogenesis of invertebrates and vertebrates, and they play large roles in shaping the body plan during development. Our focus is on the presumptive mesodermal and neural tissues of the Xenopus (frog) embryo, tissues for which some physical measurements have been made. We discuss the physical aspects of how polarized cell motility, oriented along future tissue axes, generate the forces that drive oriented cell intercalation and how this intercalation results in convergence and extension or convergence and thickening of the tissue. Our goal is to identify aspects of these morphogenic movements for further biophysical, molecular and cell biological, and modeling studies

  13. Root resorption

    DEFF Research Database (Denmark)

    Kjaer, Inger

    2014-01-01

    Introduction: This paper summarizes the different conditions, which have a well-known influence on the resorption of tooth roots, exemplified by trauma and orthodontic treatment. The concept of the paper is to summarize and explain symptoms and signs of importance for avoiding resorption during...... orthodontic treatment. The Hypothesis: The hypothesis in this paper is that three different tissue layers covering the root in the so-called periroot sheet can explain signs and symptoms of importance for avoiding root resorption during orthodontic treatment. These different tissue layers are; outermost......-an ectodermal tissue layer (Malassez′s epithelium), a middle layer-composed by the collagen-mesodermal tissue layer, and an innermost root-close innervation layer. Abnormalities in one of these tissue layers are thought to cause inflammatory processes in the periodontal membrane comparable to inflammatory...

  14. Temporal Ordering of Dynamic Expression Data from Detailed Spatial Expression Maps

    DEFF Research Database (Denmark)

    Bailey, Charlotte S L; Bone, Robert A; Murray, Philip J

    2017-01-01

    During somitogenesis, pairs of epithelial somites form in a progressive manner, budding off from the anterior end of the pre-somitic mesoderm (PSM) with a strict species-specific periodicity. The periodicity of the process is regulated by a molecular oscillator, known as the "segmentation clock......," acting in the PSM cells. This clock drives the oscillatory patterns of gene expression across the PSM in a posterior-anterior direction. These so-called clock genes are key components of three signaling pathways: Wnt, Notch, and fibroblast growth factor (FGF). In addition, Notch signaling is essential...... labile, and its phosphorylation-dependent turnover acts to restrict Notch signaling. The profile of NICD production (and degradation) in the PSM is known to be oscillatory and to resemble that of a clock gene. We recently reported that both the Notch receptor and the Delta ligand, which mediate...

  15. The association of a dysmorphic pelvis, absence of pubic rami, hip dysplasia, and genitourinary anomalies.

    Science.gov (United States)

    Bashyal, Ravi K; Malchau, Henrik; Nimkin, Katherine; Holmes, Lewis B

    2012-01-01

    There have been reports of children who had absence of the pubic rami, hip dysplasia, and genitourinary anomalies. We describe a 44-year-old woman with severe hip dysplasia, bilateral chronic congenital hip dislocations, abnormal development of the entire pelvis, and absence of the pubic rami in association with absence of the uterus. We present an individual who has abnormal development of the entire pelvis, including absence of the pubic rami, and genitourinary anomalies. We suggest that this is a rare pattern of associated anomalies confined to a localized region of the body. Potential underlying developmental abnormalities include somatic mutations which affected the mesodermal cells from which the pelvis and mullerian structures develop. Copyright © 2011 Wiley Periodicals, Inc.

  16. Mesenchymal Stem Cells and Cutaneous Wound Healing: Current Evidence and Future Potential

    Directory of Open Access Journals (Sweden)

    M. Isakson

    2015-01-01

    Full Text Available Human skin is a remarkable organ that sustains insult and injury throughout life. The ability of skin to expeditiously repair wounds is paramount to survival. With an aging global population, coupled with a rise in the prevalence of conditions such as diabetes, chronic wounds represent a significant biomedical burden. Mesenchymal stem cells (MSC, a progenitor cell population of the mesoderm lineage, have been shown to be significant mediators in inflammatory environments. Preclinical studies of MSC in various animal wound healing models point towards a putative therapy. This review examines the body of evidence suggesting that MSC accelerate wound healing in both clinical and preclinical studies and also the possible mechanisms controlling its efficacy. The delivery of a cellular therapy to the masses presents many challenges from a safety, ethical, and regulatory point of view. Some of the issues surrounding the introduction of MSC as a medicinal product are also delineated in this review.

  17. Unusual contiguous soft tissue spread of advanced malignant mesothelioma detected by FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yu Yang; Edwards, Jamie; Williams, Hadyn; Hao, Zhong Lin; Khleif, Samir; Pucar, Darko [Medical College of Georgia at Augusta UniversityAugusta (United States)

    2017-06-15

    Malignant pleural mesothelioma (MPM) is a tumor of mesodermal origin that arises from the serosa of the pleura, peritoneum, pericardium or tunica vaginalis. MPM is well known to have a poor prognosis with a median survival time of 12 months. Accurate diagnosis, staging and restaging of MPM are crucial with [18F] flurodeoxy-D-glucose positron emission tomography (FDG PET/CT) playing an increasingly important role. Here we report a case of MPM with unusual contiguous soft tissue spread of the tumor along the dermal and fascial planes characterized by PET/CT. Given that the loco-regional tumor in the thorax was under control on PET/CT, the death of the patient was most likely associated with physiologic or metabolic causes associated with an extra-thoracic tumor.

  18. Cutaneous Presentation of Mesothelioma With a Sarcomatoid Transformation.

    Science.gov (United States)

    Klebanov, Nikolai; Reddy, Bobby Y; Husain, Sameera; Silvers, David N; Grossman, Marc E; Tsao, Hensin

    2018-05-01

    Malignant pleural mesothelioma is a rare neoplasm of mesodermal origin. Cutaneous involvement of malignant pleural mesothelioma is a very rare entity, with only 11 cases reported in the literature. Here, we describe the case of a 75-year-old man with stage IV epithelioid pleural mesothelioma, presenting with a cutaneous eruption 5 months after initial diagnosis, which revealed sarcomatoid features on skin biopsy. Histological analysis of malignancy progression through immunohistochemical staining of the pleural, lymph node, and skin tissue revealed gradual loss of calretinin and gain of desmin, supporting a transformation from epithelioid to sarcomatoid tissue. To our knowledge, this is the first reported case of an epithelioid to sarcomatoid transformation of malignant pleural mesothelioma manifesting in a cutaneous presentation.

  19. Benign fibrous mesothelioma of the pleura: MR study and pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Padovani, B. [Service Central de Radiologie, Hopital Pasteur, Nice (France); Mouroux, J. [Service de Chirurgie Thoracique, Hopital Pasteur, Nice (France); Raffaelli, C. [Service Central de Radiologie, Hopital Pasteur, Nice (France); Huys, C. [Service Central de Radiologie, Hopital Pasteur, Nice (France); Chanalet, S. [Service Central de Radiologie, Hopital Pasteur, Nice (France); Michiels, J.F. [Service d`Anatomie Pathologique, Hopital Pasteur, Nice (France); Brunner, P. [Service Central de Radiologie, Hopital Pasteur, Nice (France); Bruneton, J.N. [Service Central de Radiologie, Hopital Pasteur, Nice (France)

    1996-08-01

    Benign fibrous mesothelioma of the pleura is a rare tumor of mesodermal origin. We describe the MR findings in three pathologically proven cases. All three tumors were imaged by MR as well-circumscribed lesions with smooth margins in contact with the pleura, but without chest wall invasion. Their low signal intensity on T1- and T2-weighted sequences reflect their fibrous nature. In one case a pedicle connecting the tumor to the chest wall was visualized on a sagittal MR scan. In two cases gadolinium-enhanced T1-weighted gradient echo sequences revealed intense contrast uptake by the tumor correlated with the intratumoral hypervascularization noted by histologic examination. Although the number of cases presented is small, MR seems to be the most accurate imaging modality in the assessment of the diagnosis. (orig.). With 4 figs., 1 tab.

  20. Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

    Horwood, Nicole J.; Dazzi, Francesco; Zaher, Walid

    2012-01-01

    and differentiation of hematopoietic stem cells (HSC) and hematopoiesis. These cells have been described as important immunoregulators due to their ability to suppress T cells proliferation. MSC can also directly contribute to tissue repair by migrating to sites of injury and providing a source of cells......Mesenchymal stem cells (MSC) are stem cell populations present among the bone marrow stroma and a number of other tissues that are capable of multi-lineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. MSC provide supportive stroma for growth...... for differentiation and/or providing bystander support for resident stromal cells. This chapter discusses the cellular and molecular properties of MSC, the mechanisms by which they can modulate immune responses and the clinical applications of MSC in disorders such as graft-versus-host disease and aplastic anaemia...

  1. The epigenetic modifier Fam208a is required to maintain epiblast cell fitness

    Czech Academy of Sciences Publication Activity Database

    Bhargava, Shohag; Cox, B.; Polydorou, Ch.; Grešáková, Veronika; Kořínek, Vladimír; Strnad, Hynek; Sedláček, Radislav; Epp, Trevor Allan; Chawengsaksophak, Kallayanee

    2017-01-01

    Roč. 7, léto (2017), č. článku 9322. ISSN 2045-2322 R&D Projects: GA ČR GA15-23165S; GA MŠk LO1419; GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk ED2.1.00/19.0395; GA MŠk(CZ) LM2011032; GA MŠk(CZ) LM2015040; GA MŠk(CZ) LQ1604 Institutional support: RVO:68378050 Keywords : bone morphogenetic protein-4 * position-effect variegation * gastrulating mouse embryo * anterior-posterior axis * mesoderm differentiation * expression pattern * mice lacking * postimplantation development * definitive endoderm * primitive streak Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 4.259, year: 2016

  2. Development of the carapacial ridge: implications for the evolution of genetic networks in turtle shell development.

    Science.gov (United States)

    Moustakas, Jacqueline E

    2008-01-01

    Paleontologists and neontologists have long looked to development to understand the homologies of the dermal bones that form the "armor" of turtles, crocodiles, armadillos, and other vertebrates. This study shows molecular evidence supporting a dermomyotomal identity for the mesenchyme of the turtle carapacial ridge. The mesenchyme of the carapace primordium expresses Pax3, Twist1, Dermo1, En1, Sim1, and Gremlin at early stages and before overt ossification expresses Pax1. A hypothesis is proposed that this mesenchyme forms dermal bone in the turtle carapace. A comparison of regulatory gene expression in the primordia of the turtle carapace, the vertebrate limb, and the vertebral column implies the exaptation of key genetic networks in the development of the turtle shell. This work establishes a new role for this mesodermal compartment and highlights the importance of changes in genetic regulation in the evolution of morphology.

  3. Myosin heavy chain-like localizes at cell contact sites during Drosophila myoblast fusion and interacts in vitro with Rolling pebbles 7

    Energy Technology Data Exchange (ETDEWEB)

    Bonn, Bettina R.; Rudolf, Anja; Hornbruch-Freitag, Christina; Daum, Gabor; Kuckwa, Jessica; Kastl, Lena; Buttgereit, Detlev [Developmental Biology, Department of Biology, Philipps-Universität Marburg, Karl-von-Frisch-Strasse 8, 35037 Marburg (Germany); Renkawitz-Pohl, Renate, E-mail: renkawit@biologie.uni-marburg.de [Developmental Biology, Department of Biology, Philipps-Universität Marburg, Karl-von-Frisch-Strasse 8, 35037 Marburg (Germany)

    2013-02-15

    Besides representing the sarcomeric thick filaments, myosins are involved in many cellular transport and motility processes. Myosin heavy chains are grouped into 18 classes. Here we show that in Drosophila, the unconventional group XVIII myosin heavy chain-like (Mhcl) is transcribed in the mesoderm of embryos, most prominently in founder cells (FCs). An ectopically expressed GFP-tagged Mhcl localizes in the growing muscle at cell–cell contacts towards the attached fusion competent myoblast (FCM). We further show that Mhcl interacts in vitro with the essential fusion protein Rolling pebbles 7 (Rols7), which is part of a protein complex established at cell contact sites (Fusion-restricted Myogenic-Adhesive Structure or FuRMAS). Here, branched F-actin is likely needed to widen the fusion pore and to integrate the myoblast into the growing muscle. We show that the localization of Mhcl is dependent on the presence of Rols7, and we postulate that Mhcl acts at the FuRMAS as an actin motor protein. We further show that Mhcl deficient embryos develop a wild-type musculature. We thus propose that Mhcl functions redundantly to other myosin heavy chains in myoblasts. Lastly, we found that the protein is detectable adjacent to the sarcomeric Z-discs, suggesting an additional function in mature muscles. - Highlights: ► The class XVIII myosin encoding gene Mhcl is transcribed in the mesoderm. ► Mhcl localization at contact sites of fusing myoblasts depends on Rols7. ► Mhcl interacts in vitro with Rols7 which is essential for myogenesis. ► Functional redundancy with other myosins is likely as mutants show no muscle defects. ► Mhcl localizes adjacent to Z-discs of sarcomeres and might support muscle integrity.

  4. Expression-guided in silico evaluation of candidate cis regulatory codes for Drosophila muscle founder cells.

    Directory of Open Access Journals (Sweden)

    Anthony A Philippakis

    2006-05-01

    Full Text Available While combinatorial models of transcriptional regulation can be inferred for metazoan systems from a priori biological knowledge, validation requires extensive and time-consuming experimental work. Thus, there is a need for computational methods that can evaluate hypothesized cis regulatory codes before the difficult task of experimental verification is undertaken. We have developed a novel computational framework (termed "CodeFinder" that integrates transcription factor binding site and gene expression information to evaluate whether a hypothesized transcriptional regulatory model (TRM; i.e., a set of co-regulating transcription factors is likely to target a given set of co-expressed genes. Our basic approach is to simultaneously predict cis regulatory modules (CRMs associated with a given gene set and quantify the enrichment for combinatorial subsets of transcription factor binding site motifs comprising the hypothesized TRM within these predicted CRMs. As a model system, we have examined a TRM experimentally demonstrated to drive the expression of two genes in a sub-population of cells in the developing Drosophila mesoderm, the somatic muscle founder cells. This TRM was previously hypothesized to be a general mode of regulation for genes expressed in this cell population. In contrast, the present analyses suggest that a modified form of this cis regulatory code applies to only a subset of founder cell genes, those whose gene expression responds to specific genetic perturbations in a similar manner to the gene on which the original model was based. We have confirmed this hypothesis by experimentally discovering six (out of 12 tested new CRMs driving expression in the embryonic mesoderm, four of which drive expression in founder cells.

  5. Rac1 modulates cardiomyocyte adhesion during mouse embryonic development

    Energy Technology Data Exchange (ETDEWEB)

    Abu-Issa, Radwan, E-mail: rabuissa@umich.edu

    2015-01-24

    Highlights: • Conditional knockout of Rac1 using Nkx2.5 Cre line is lethal at E13.5. • The myocardium of the mutant is thin and disorganized. • The phenotype is not due to cardiomyocyte low proliferation or apoptosis. • The phenotype is due to specific defect in cardiomyocyte adhesion. - Abstract: Rac1, a member of the Rho subfamily of small GTPases, is involved in morphogenesis and differentiation of many cell types. Here we define a role of Rac1 in cardiac development by specifically deleting Rac1 in the pre-cardiac mesoderm using the Nkx2.5-Cre transgenic driver line. Rac1-conditional knockout embryos initiate heart development normally until embryonic day 11.5 (E11.5); their cardiac mesoderm is specified, and the heart tube is formed and looped. However, by E12.5-E13.5 the mutant hearts start failing and embryos develop edema and hemorrhage which is probably the cause for the lethality observed soon after. The hearts of Rac1-cKO embryos exhibit disorganized and thin myocardial walls and defects in outflow tract alignment. No significant differences of cardiomyocyte death or proliferation were found between developing control and mutant embryos. To uncover the role of Rac1 in the heart, E11.5 primary heart cells were cultured and analyzed in vitro. Rac1-deficient cardiomyocytes were less spread, round and loosely attached to the substrate and to each other implying that Rac1-mediated signaling is required for appropriate cell–cell and/or cellmatrix adhesion during cardiac development.

  6. Rac1 modulates cardiomyocyte adhesion during mouse embryonic development

    International Nuclear Information System (INIS)

    Abu-Issa, Radwan

    2015-01-01

    Highlights: • Conditional knockout of Rac1 using Nkx2.5 Cre line is lethal at E13.5. • The myocardium of the mutant is thin and disorganized. • The phenotype is not due to cardiomyocyte low proliferation or apoptosis. • The phenotype is due to specific defect in cardiomyocyte adhesion. - Abstract: Rac1, a member of the Rho subfamily of small GTPases, is involved in morphogenesis and differentiation of many cell types. Here we define a role of Rac1 in cardiac development by specifically deleting Rac1 in the pre-cardiac mesoderm using the Nkx2.5-Cre transgenic driver line. Rac1-conditional knockout embryos initiate heart development normally until embryonic day 11.5 (E11.5); their cardiac mesoderm is specified, and the heart tube is formed and looped. However, by E12.5-E13.5 the mutant hearts start failing and embryos develop edema and hemorrhage which is probably the cause for the lethality observed soon after. The hearts of Rac1-cKO embryos exhibit disorganized and thin myocardial walls and defects in outflow tract alignment. No significant differences of cardiomyocyte death or proliferation were found between developing control and mutant embryos. To uncover the role of Rac1 in the heart, E11.5 primary heart cells were cultured and analyzed in vitro. Rac1-deficient cardiomyocytes were less spread, round and loosely attached to the substrate and to each other implying that Rac1-mediated signaling is required for appropriate cell–cell and/or cellmatrix adhesion during cardiac development

  7. Efficient Commitment to Functional CD34+ Progenitor Cells from Human Bone Marrow Mesenchymal Stem-Cell-Derived Induced Pluripotent Stem Cells

    Science.gov (United States)

    Xu, Yulin; Liu, Lizhen; Zhang, Lifei; Fu, Shan; Hu, Yongxian; Wang, Yingjia; Fu, Huarui; Wu, Kangni; Xiao, Haowen; Liu, Senquan; Yu, Xiaohong; Zheng, Weiyan; Feng, Bo; Huang, He

    2012-01-01

    The efficient commitment of a specialized cell type from induced pluripotent stem cells (iPSCs) without contamination from unknown substances is crucial to their use in clinical applications. Here, we propose that CD34+ progenitor cells, which retain hematopoietic and endothelial cell potential, could be efficiently obtained from iPSCs derived from human bone marrow mesenchymal stem cells (hBMMSC-iPSCs) with defined factors. By treatment with a cocktail containing mesodermal, hematopoietic, and endothelial inducers (BMP4, SCF, and VEGF, respectively) for 5 days, hBMMSC-iPSCs expressed the mesodermal transcription factors Brachyury and GATA-2 at higher levels than untreated groups (P<0.05). After culturing with another hematopoietic and endothelial inducer cocktail, including SCF, Flt3L, VEGF and IL-3, for an additional 7–9 days, CD34+ progenitor cells, which were undetectable in the initial iPSC cultures, reached nearly 20% of the total culture. This was greater than the relative number of progenitor cells produced from human-skin-fibroblast-derived iPSCs (hFib-iPSCs) or from the spontaneous differentiation groups (P<0.05), as assessed by flow cytometry analysis. These induced cells expressed hematopoietic transcription factors TAL-1 and SCL. They developed into various hematopoietic colonies when exposed to semisolid media with hematopoietic cytokines such as EPO and G-CSF. Hematopoietic cell lineages were identified by phenotype analysis with Wright-Giemsa staining. The endothelial potential of the cells was also verified by the confirmation of the formation of vascular tube-like structures and the expression of endothelial-specific markers CD31 and VE-CADHERIN. Efficient induction of CD34+ progenitor cells, which retain hematopoietic and endothelial cell potential with defined factors, provides an opportunity to obtain patient-specific cells for iPSC therapy and a useful model for the study of the mechanisms of hematopoiesis and drug screening. PMID:22496789

  8. A Zebrafish Model of Axenfeld-Rieger Syndrome Reveals That pitx2 Regulation by Retinoic Acid Is Essential for Ocular and Craniofacial Development

    Science.gov (United States)

    Bohnsack, Brenda L.; Kasprick, Daniel S.; Kish, Phillip E.; Goldman, Daniel

    2012-01-01

    Purpose. The homeobox transcription factor PITX2 is a known regulator of mammalian ocular development, and human PITX2 mutations are associated with Axenfeld-Rieger syndrome (ARS). However, the treatment of patients with ARS remains mostly supportive and palliative. Methods. The authors used molecular genetic, pharmacologic, and embryologic techniques to study the biology of ARS in a zebrafish model that uses transgenes to mark neural crest and muscle cells in the head. Results. The authors demonstrated in vivo that pitx2 is a key downstream target of retinoic acid (RA) in craniofacial development, and this pathway is required for coordinating neural crest, mesoderm, and ocular development. pitx2a knockdown using morpholino oligonucleotides disrupts jaw and pharyngeal arch formation and recapitulates ocular characteristics of ARS, including corneal and iris stroma maldevelopment. These phenotypes could be rescued with human PITX2A mRNA, demonstrating the specificity of the knockdown and evolutionary conservation of pitx2a function. Expression of the ARS dominant negative human PITX2A K50E allele also caused ARS-like phenotypes. Similarly, inhibition of RA synthesis in the developing eye (genetic or pharmacologic) disrupted craniofacial and ocular development, and human PITX2A mRNA partially rescued these defects. Conclusions. RA regulation of pitx2 is essential for coordinating interactions among neural crest, mesoderm, and developing eye. The marked evolutionary conservation of Pitx2 function in eye and craniofacial development makes zebrafish a potentially powerful model of ARS, amenable to in vivo experimentation and development of potential therapies. PMID:22125274

  9. Role of Hepatic-Specific Transcription Factors and Polycomb Repressive Complex 2 during Induction of Fibroblasts to Hepatic Fate.

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    Shima Rastegar-Pouyani

    Full Text Available Direct reprogramming using defined sets of transcription factors (TFs is a recent strategy for generating induced hepatocytes (iHeps from fibroblasts for use in regenerative medicine and drug development. Comprehensive studies detailing the regulatory role of TFs during this reprogramming process could help increase its efficiency. This study aimed to find the TFs with the greatest influences on the generation of iHeps from fibroblasts, and to further understand their roles in the regulation of the gene expression program. Here, we used systems biology approaches to analyze high quality expression data sets in combination with TF-binding sites data and protein-protein interactions data during the direct reprogramming of fibroblasts to iHeps. Our results revealed two main patterns for differentially expressed genes (DEGs: up-regulated genes were categorized as hepatic-specific pattern, and down-regulated genes were categorized as mesoderm- and fibroblast-specific pattern. Interestingly, hepatic-specific genes co-expressed and were regulated by hepatic-specific TFs, specifically Hnf4a and Foxa2. Conversely, the mesoderm- and fibroblast-specific pattern was mainly silenced by polycomb repressive complex 2 (PRC2 members, including Suz12, Mtf2, Ezh2, and Jarid2. Independent analysis of both the gene and core regulatory network of DE-TFs showed significant roles for Hnf4a, Foxa2, and PRC2 members in the regulation of the gene expression program and in biological processes during the direct conversion process. Altogether, using systems biology approaches, we clarified the role of Hnf4a and Foxa2 as hepatic-specific TFs, and for the first time, introduced the PRC2 complex as the main regulator that favors the direct reprogramming process in cooperation with hepatic-specific factors.

  10. Cell population structure prior to bifurcation predicts efficiency of directed differentiation in human induced pluripotent cells.

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    Bargaje, Rhishikesh; Trachana, Kalliopi; Shelton, Martin N; McGinnis, Christopher S; Zhou, Joseph X; Chadick, Cora; Cook, Savannah; Cavanaugh, Christopher; Huang, Sui; Hood, Leroy

    2017-02-28

    Steering the differentiation of induced pluripotent stem cells (iPSCs) toward specific cell types is crucial for patient-specific disease modeling and drug testing. This effort requires the capacity to predict and control when and how multipotent progenitor cells commit to the desired cell fate. Cell fate commitment represents a critical state transition or "tipping point" at which complex systems undergo a sudden qualitative shift. To characterize such transitions during iPSC to cardiomyocyte differentiation, we analyzed the gene expression patterns of 96 developmental genes at single-cell resolution. We identified a bifurcation event early in the trajectory when a primitive streak-like cell population segregated into the mesodermal and endodermal lineages. Before this branching point, we could detect the signature of an imminent critical transition: increase in cell heterogeneity and coordination of gene expression. Correlation analysis of gene expression profiles at the tipping point indicates transcription factors that drive the state transition toward each alternative cell fate and their relationships with specific phenotypic readouts. The latter helps us to facilitate small molecule screening for differentiation efficiency. To this end, we set up an analysis of cell population structure at the tipping point after systematic variation of the protocol to bias the differentiation toward mesodermal or endodermal cell lineage. We were able to predict the proportion of cardiomyocytes many days before cells manifest the differentiated phenotype. The analysis of cell populations undergoing a critical state transition thus affords a tool to forecast cell fate outcomes and can be used to optimize differentiation protocols to obtain desired cell populations.

  11. Chiari malformation type I: a case-control association study of 58 developmental genes.

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    Aintzane Urbizu

    Full Text Available Chiari malformation type I (CMI is a disorder characterized by hindbrain overcrowding into an underdeveloped posterior cranial fossa (PCF, often causing progressive neurological symptoms. The etiology of CMI remains unclear and is most likely multifactorial. A putative genetic contribution to CMI is suggested by familial aggregation and twin studies. Experimental models and human morphometric studies have suggested an underlying paraxial mesoderm insufficiency. We performed a case-control association study of 303 tag single nucleotide polymorphisms (SNP across 58 candidate genes involved in early paraxial mesoderm development in a sample of 415 CMI patients and 524 sex-matched controls. A subgroup of patients diagnosed with classical, small-PCF CMI by means of MRI-based PCF morphometry (n = 186, underwent additional analysis. The genes selected are involved in signalling gradients occurring during segmental patterning of the occipital somites (FGF8, Wnt, and retinoic acid pathways and from bone morphogenetic proteins or BMP, Notch, Cdx and Hox pathways or in placental angiogenesis, sclerotome development or CMI-associated syndromes. Single-marker analysis identified nominal associations with 18 SNPs in 14 genes (CDX1, FLT1, RARG, NKD2, MSGN1, RBPJ1, FGFR1, RDH10, NOG, RARA, LFNG, KDR, ALDH1A2, BMPR1A considering the whole CMI sample. None of these overcame corrections for multiple comparisons, in contrast with four SNPs in CDX1, FLT1 and ALDH1A2 in the classical CMI group. Multiple marker analysis identified a risk haplotype for classical CMI in ALDH1A2 and CDX1. Furthermore, we analyzed the possible contributions of the most significantly associated SNPs to different PCF morphometric traits. These findings suggest that common variants in genes involved in somitogenesis and fetal vascular development may confer susceptibility to CMI.

  12. Why is cytoskeletal contraction required for cardiac fusion before but not after looping begins?

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    Shi, Yunfei; Taber, Larry A; Varner, Victor D

    2015-01-01

    Cytoskeletal contraction is crucial to numerous morphogenetic processes, but its role in early heart development is poorly understood. Studies in chick embryos have shown that inhibiting myosin-II-based contraction prior to Hamburger–Hamilton (HH) stage 10 (33 h incubation) impedes fusion of the mesodermal heart fields that create the primitive heart tube (HT), as well as the ensuing process of cardiac looping. If contraction is inhibited at or after looping begins at HH10, however, fusion and looping proceed relatively normally. To explore the mechanisms behind this seemingly fundamental change in behavior, we measured spatiotemporal distributions of tissue stiffness, stress, and strain around the anterior intestinal portal (AIP), the opening to the foregut where contraction and cardiac fusion occur. The results indicate that stiffness and tangential tension decreased bilaterally along the AIP with distance from the embryonic midline. The gradients in stiffness and tension, as well as strain rate, increased to peaks at HH9 (30 h) and decreased afterward. Exposure to the myosin II inhibitor blebbistatin reduced these effects, suggesting that they are mainly generated by active cytoskeletal contraction, and finite-element modeling indicates that the measured mechanical gradients are consistent with a relatively uniform contraction of the endodermal layer in conjunction with constraints imposed by the attached mesoderm. Taken together, our results suggest that, before HH10, endodermal contraction pulls the bilateral heart fields toward the midline where they fuse to create the HT. By HH10, however, the fusion process is far enough along to enable apposing cardiac progenitor cells to keep ‘zipping’ together during looping without the need for continued high contractile forces. These findings should shed new light on a perplexing question in early heart development. (paper)

  13. miR-200c and GATA binding protein 4 regulate human embryonic stem cell renewal and differentiation

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    Hsiao-Ning Huang

    2014-03-01

    Full Text Available Human embryonic stem cells (hESCs are functionally unique for their self-renewal ability and pluripotency, but the molecular mechanisms giving rise to these properties are not fully understood. hESCs can differentiate into embryoid bodies (EBs containing ectoderm, mesoderm, and endoderm. In the miR-200 family, miR-200c was especially enriched in undifferentiated hESCs and significantly downregulated in EBs. The knockdown of the miR-200c in hESCs downregulated Nanog expression, upregulated GATA binding protein 4 (GATA4 expression, and induced hESC apoptosis. The knockdown of GATA4 rescued hESC apoptosis induced by downregulation of miR-200c. miR-200c directly targeted the 3′-untranslated region of GATA4. Interestingly, the downregulation of GATA4 significantly inhibited EB formation in hESCs. Overexpression of miR-200c inhibited EB formation and repressed the expression of ectoderm, endoderm, and mesoderm markers, which could partially be rescued by ectopic expression of GATA4. Fibroblast growth factor (FGF and activin A/nodal can sustain hESC renewal in the absence of feeder layer. Inhibition of transforming growth factor-β (TGF-β/activin A/nodal signaling by SB431542 treatment downregulated the expression of miR-200c. Overexpression of miR-200c partially rescued the expression of Nanog/phospho-Smad2 that was downregulated by SB431542 treatment. Our observations have uncovered novel functions of miR-200c and GATA4 in regulating hESC renewal and differentiation.

  14. Live Imaging-Based Model Selection Reveals Periodic Regulation of the Stochastic G1/S Phase Transition in Vertebrate Axial Development

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    Kurokawa, Hiroshi; Sakaue-Sawano, Asako; Imamura, Takeshi; Miyawaki, Atsushi; Iimura, Tadahiro

    2014-01-01

    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 the

  15. Characterization of hey bHLH genes in teleost fish.

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    Winkler, Christoph; Elmasri, Harun; Klamt, Barbara; Volff, Jean-Nicolas; Gessler, Manfred

    2003-11-01

    Hairy-related basic helix-loop-helix (bHLH) transcription factors are targets of Delta-Notch signaling and represent essential components for a number of cell fate decisions during vertebrate embryogenesis. Hey genes encode a subfamily of hairy-related proteins that have been implicated in processes like somitogenesis, blood vessel and heart development. We have identified and characterized hey genes in three teleost fish lineages using degenerate PCR and database searches. Phylogenetic analysis of Hey proteins suggests a complex pattern of evolution with high divergence of hey2 in Takifugu rubripes (Fugu, Japanese pufferfish) and possibly loss in the related Tetraodon nigroviridis (the freshwater pufferfish). In addition, duplication of hey1 in both pufferfishes, Fugu and Tetraodon, was observed. Conversely, zebrafish (Danio rerio) has the same complement of three hey genes as known from mammals. All three hey genes show much more restricted gene expression profiles in zebrafish when compared to mouse. Importantly, while all three murine Hey genes are expressed in overlapping patterns in the presomitic mesoderm (PSM) and somites, in zebrafish only hey1 shows PSM and somite expression in a highly dynamic fashion. Therefore, while overlapping expression might account for redundancy of hey function in higher vertebrates, this is unlikely to be the case in zebrafish. In deltaD (dlD) deficient after-eight zebrafish mutants, the dynamic expression of hey1 in the PSM is impaired and completely lost in newly formed somitomeres. Overexpression of dlD on the other hand results in the ectopic expression of hey1 in the axial mesoderm. Hence, hey1 represents a target of Delta-Notch signaling dynamically expressed during somite formation in zebrafish.

  16. An integrated strategy for analyzing the unique developmental programs of different myoblast subtypes.

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    2006-02-01

    Full Text Available An important but largely unmet challenge in understanding the mechanisms that govern the formation of specific organs is to decipher the complex and dynamic genetic programs exhibited by the diversity of cell types within the tissue of interest. Here, we use an integrated genetic, genomic, and computational strategy to comprehensively determine the molecular identities of distinct myoblast subpopulations within the Drosophila embryonic mesoderm at the time that cell fates are initially specified. A compendium of gene expression profiles was generated for primary mesodermal cells purified by flow cytometry from appropriately staged wild-type embryos and from 12 genotypes in which myogenesis was selectively and predictably perturbed. A statistical meta-analysis of these pooled datasets--based on expected trends in gene expression and on the relative contribution of each genotype to the detection of known muscle genes--provisionally assigned hundreds of differentially expressed genes to particular myoblast subtypes. Whole embryo in situ hybridizations were then used to validate the majority of these predictions, thereby enabling true-positive detection rates to be estimated for the microarray data. This combined analysis reveals that myoblasts exhibit much greater gene expression heterogeneity and overall complexity than was previously appreciated. Moreover, it implicates the involvement of large numbers of uncharacterized, differentially expressed genes in myogenic specification and subsequent morphogenesis. These findings also underscore a requirement for considerable regulatory specificity for generating diverse myoblast identities. Finally, to illustrate how the developmental functions of newly identified myoblast genes can be efficiently surveyed, a rapid RNA interference assay that can be scored in living embryos was developed and applied to selected genes. This integrated strategy for examining embryonic gene expression and function provides

  17. PCL-PDMS-PCL copolymer-based microspheres mediate cardiovascular differentiation from embryonic stem cells

    Science.gov (United States)

    Song, Liqing

    Poly-epsilon-caprolactone (PCL) based copolymers have received much attention as drug or growth factor delivery carriers and tissue engineering scaffolds due to their biocompatibility, biodegradability, and tunable biophysical properties. Copolymers of PCL and polydimethylsiloxane (PDMS) also have shape memory behaviors and can be made into thermoresponsive shape memory polymers for various biomedical applications such as smart sutures and vascular stents. However, the influence of biophysical properties of PCL-PDMS-PCL copolymers on stem cell lineage commitment is not well understood. In this study, PDMS was used as soft segments of varying length to tailor the biophysical properties of PCL-based co-polymers. While low elastic modulus (embryonic stem cells, the range of 60-100 MPa PCL-PDMS-PCL showed little influence on the differentiation. Then different size (30-140 mum) of microspheres were fabricated from PCL-PDMS-PCL copolymers and incorporated within embryoid bodies (EBs). Mesoderm differentiation was induced using bone morphogenetic protein (BMP)-4 for cardiovascular differentiation. Differential expressions of mesoderm progenitor marker KDR and vascular markers CD31 and VE-cadherin were observed for the cells differentiated from EBs incorporated with microspheres of different size, while little difference was observed for cardiac marker alpha-actinin expression. Small size of microspheres (30 mum) resulted in higher expression of KDR while medium size of microspheres (94 mum) resulted in higher CD31 and VE-cadherin expression. This study indicated that the biophysical properties of PCL-based copolymers impacted stem cell lineage commitment, which should be considered for drug delivery and tissue engineering applications.

  18. Development of analyzing system for gene functions of nerve growth factor using {gamma}-radiation induced mutants of Oryzias latipes

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    Araki, Kazuo; Nagoya, Hiroyuki; Okamoto, Hiroyuki [National Research Inst. of Aquaculture, Mie (Japan)

    1999-02-01

    Oryzias latipes mutants that have abnormalities in the nervous system were screened with an aim to develop a model system to investigate the functions of nerve growing factor gene. When male O. latipes was exposed to {gamma}-ray at a dose of 4.5 to 5.0 Gy, its mutants were most effectively produced. Then, F{sub 2} pairs that might produce offspring with abnormalities in the brain, chorda and tail were selected and cultured successively. The embryos of thus obtained mutants, nt and ut were histologically observed at various stages of their developments and these mutants were found to have abnormalities in the chorda. Then, the expressions of Brachury and HNF3{beta} genes, which possibly control the expression of nerve growth factor gene and closely mediate the embryogenesis were investigated in the chorda and the mesoderm of these mutants by in situ hybridization method. Brachury gene in nt mutant as well as the wild strain was expressed in the region of the tail end, whereas HNF3{beta} gene of nt was not expressed in the chordal end and its adjacent mesoderm. This suggests that the gene of growth factor of which expression is induced by HNF3{beta}, might be inactive in the caudal region of the embryo. When these mutants with abnormalities in caudal formation were crossed each other, any abnormality was not observed in the chordal formation of the offspring. Therefore, it was concluded that the abnormalities in the chordal formation of these mutants might be caused by a mutation at different genes. (M.N.)

  19. Activin-A and Bmp4 levels modulate cell type specification during CHIR-induced cardiomyogenesis.

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    Min-Su Kim

    Full Text Available The use of human pluripotent cell progeny for cardiac disease modeling, drug testing and therapeutics requires the ability to efficiently induce pluripotent cells into the cardiomyogenic lineage. Although direct activation of the Activin-A and/or Bmp pathways with growth factors yields context-dependent success, recent studies have shown that induction of Wnt signaling using low molecular weight molecules such as CHIR, which in turn induces the Activin-A and Bmp pathways, is widely effective. To further enhance the reproducibility of CHIR-induced cardiomyogenesis, and to ultimately promote myocyte maturation, we are using exogenous growth factors to optimize cardiomyogenic signaling downstream of CHIR induction. As indicated by RNA-seq, induction with CHIR during Day 1 (Days 0-1 was followed by immediate expression of Nodal ligands and receptors, followed later by Bmp ligands and receptors. Co-induction with CHIR and high levels of the Nodal mimetic Activin-A (50-100 ng/ml during Day 0-1 efficiently induced definitive endoderm, whereas CHIR supplemented with Activin-A at low levels (10 ng/ml consistently improved cardiomyogenic efficiency, even when CHIR alone was ineffective. Moreover, co-induction using CHIR and low levels of Activin-A apparently increased the rate of cardiomyogenesis, as indicated by the initial appearance of rhythmically beating cells by Day 6 instead of Day 8. By contrast, co-induction with CHIR plus low levels (3-10 ng/ml of Bmp4 during Day 0-1 consistently and strongly inhibited cardiomyogenesis. These findings, which demonstrate that cardiomyogenic efficacy is improved by optimizing levels of CHIR-induced growth factors when applied in accord with their sequence of endogenous expression, are consistent with the idea that Nodal (Activin-A levels toggle the entry of cells into the endodermal or mesodermal lineages, while Bmp levels regulate subsequent allocation into mesodermal cell types.

  20. A role for mesenchyme dynamics in mouse lung branching morphogenesis.

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    Pierre Blanc

    Full Text Available Mammalian airways are highly ramified tree-like structures that develop by the repetitive branching of the lung epithelium into the surrounding mesenchyme through reciprocal interactions. Based on a morphometric analysis of the epithelial tree, it has been recently proposed that the complete branching scheme is specified early in each lineage by a programme using elementary patterning routines at specific sites and times in the developing lung. However, the coupled dynamics of both the epithelium and mesenchyme have been overlooked in this process. Using a qualitative and quantitative in vivo morphometric analysis of the E11.25 to E13.5 mouse whole right cranial lobe structure, we show that beyond the first generations, the branching stereotypy relaxes and both spatial and temporal variations are common. The branching pattern and branching rate are sensitive to the dynamic changes of the mesoderm shape that is in turn mainly dependent upon the volume and shape of the surrounding intrathoracic organs. Spatial and temporal variations of the tree architecture are related to local and subtle modifications of the mesoderm growth. Remarkably, buds never meet after suffering branching variations and continue to homogenously fill the opening spaces in the mesenchyme. Moreover despite inter-specimen variations, the growth of the epithelial tree and the mesenchyme remains highly correlated over time at the whole lobe level, implying a long-range regulation of the lung lobe morphogenesis. Together, these findings indicate that the lung epithelial tree is likely to adapt in real time to fill the available space in the mesenchyme, rather than being rigidly specified and predefined by a global programme. Our results strongly support the idea that a comprehensive understanding of lung branching mechanisms cannot be inferred from the branching pattern or behavior alone. Rather it needs to be elaborated upon with the reconsideration of mesenchyme

  1. A role for mesenchyme dynamics in mouse lung branching morphogenesis.

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    Blanc, Pierre; Coste, Karen; Pouchin, Pierre; Azaïs, Jean-Marc; Blanchon, Loïc; Gallot, Denis; Sapin, Vincent

    2012-01-01

    Mammalian airways are highly ramified tree-like structures that develop by the repetitive branching of the lung epithelium into the surrounding mesenchyme through reciprocal interactions. Based on a morphometric analysis of the epithelial tree, it has been recently proposed that the complete branching scheme is specified early in each lineage by a programme using elementary patterning routines at specific sites and times in the developing lung. However, the coupled dynamics of both the epithelium and mesenchyme have been overlooked in this process. Using a qualitative and quantitative in vivo morphometric analysis of the E11.25 to E13.5 mouse whole right cranial lobe structure, we show that beyond the first generations, the branching stereotypy relaxes and both spatial and temporal variations are common. The branching pattern and branching rate are sensitive to the dynamic changes of the mesoderm shape that is in turn mainly dependent upon the volume and shape of the surrounding intrathoracic organs. Spatial and temporal variations of the tree architecture are related to local and subtle modifications of the mesoderm growth. Remarkably, buds never meet after suffering branching variations and continue to homogenously fill the opening spaces in the mesenchyme. Moreover despite inter-specimen variations, the growth of the epithelial tree and the mesenchyme remains highly correlated over time at the whole lobe level, implying a long-range regulation of the lung lobe morphogenesis. Together, these findings indicate that the lung epithelial tree is likely to adapt in real time to fill the available space in the mesenchyme, rather than being rigidly specified and predefined by a global programme. Our results strongly support the idea that a comprehensive understanding of lung branching mechanisms cannot be inferred from the branching pattern or behavior alone. Rather it needs to be elaborated upon with the reconsideration of mesenchyme-epithelium coupled growth and lung

  2. Skeletogenic fate of zebrafish cranial and trunk neural crest.

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    Erika Kague

    Full Text Available The neural crest (NC is a major contributor to the vertebrate craniofacial skeleton, detailed in model organisms through embryological and genetic approaches, most notably in chick and mouse. Despite many similarities between these rather distant species, there are also distinct differences in the contribution of the NC, particularly to the calvariae of the skull. Lack of information about other vertebrate groups precludes an understanding of the evolutionary significance of these differences. Study of zebrafish craniofacial development has contributed substantially to understanding of cartilage and bone formation in teleosts, but there is currently little information on NC contribution to the zebrafish skeleton. Here, we employ a two-transgene system based on Cre recombinase to genetically label NC in the zebrafish. We demonstrate NC contribution to cells in the cranial ganglia and peripheral nervous system known to be NC-derived, as well as to a subset of myocardial cells. The indelible labeling also enables us to determine NC contribution to late-forming bones, including the calvariae. We confirm suspected NC origin of cartilage and bones of the viscerocranium, including cartilages such as the hyosymplectic and its replacement bones (hymandibula and symplectic and membranous bones such as the opercle. The cleithrum develops at the border of NC and mesoderm, and as an ancestral component of the pectoral girdle was predicted to be a hybrid bone composed of both NC and mesoderm tissues. However, we find no evidence of a NC contribution to the cleithrum. Similarly, in the vault of the skull, the parietal bones and the caudal portion of the frontal bones show no evidence of NC contribution. We also determine a NC origin for caudal fin lepidotrichia; the presumption is that these are derived from trunk NC, demonstrating that these cells have the ability to form bone during normal vertebrate development.

  3. Neural crest stem cell population in craniomaxillofacial development and tissue repair

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    M La Noce

    2014-10-01

    Full Text Available Neural crest cells, delaminating from the neural tube during migration, undergo an epithelial-mesenchymal transition and differentiate into several cell types strongly reinforcing the mesoderm of the craniofacial body area – giving rise to bone, cartilage and other tissues and cells of this human body area. Recent studies on craniomaxillofacial neural crest-derived cells have provided evidence for the tremendous plasticity of these cells. Actually, neural crest cells can respond and adapt to the environment in which they migrate and the cranial mesoderm plays an important role toward patterning the identity of the migrating neural crest cells. In our experience, neural crest-derived stem cells, such as dental pulp stem cells, can actively proliferate, repair bone and give rise to other tissues and cytotypes, including blood vessels, smooth muscle, adipocytes and melanocytes, highlighting that their use in tissue engineering is successful. In this review, we provide an overview of the main pathways involved in neural crest formation, delamination, migration and differentiation; and, in particular, we concentrate our attention on the translatability of the latest scientific progress. Here we try to suggest new ideas and strategies that are needed to fully develop the clinical use of these cells. This effort should involve both researchers/clinicians and improvements in good manufacturing practice procedures. It is important to address studies towards clinical application or take into consideration that studies must have an effective therapeutic prospect for humans. New approaches and ideas must be concentrated also toward stem cell recruitment and activation within the human body, overcoming the classical grafting.

  4. SAMS, a syndrome of short stature, auditory-canal atresia, mandibular hypoplasia, and skeletal abnormalities is a unique neurocristopathy caused by mutations in Goosecoid.

    Science.gov (United States)

    Parry, David A; Logan, Clare V; Stegmann, Alexander P A; Abdelhamed, Zakia A; Calder, Alistair; Khan, Shabana; Bonthron, David T; Clowes, Virginia; Sheridan, Eamonn; Ghali, Neeti; Chudley, Albert E; Dobbie, Angus; Stumpel, Constance T R M; Johnson, Colin A

    2013-12-05

    Short stature, auditory canal atresia, mandibular hypoplasia, and skeletal abnormalities (SAMS) has been reported previously to be a rare, autosomal-recessive developmental disorder with other, unique rhizomelic skeletal anomalies. These include bilateral humeral hypoplasia, humeroscapular synostosis, pelvic abnormalities, and proximal defects of the femora. To identify the genetic basis of SAMS, we used molecular karyotyping and whole-exome sequencing (WES) to study small, unrelated families. Filtering of variants from the WES data included segregation analysis followed by comparison of in-house exomes. We identified a homozygous 306 kb microdeletion and homozygous predicted null mutations of GSC, encoding Goosecoid homeobox protein, a paired-like homeodomain transcription factor. This confirms that SAMS is a human malformation syndrome resulting from GSC mutations. Previously, Goosecoid has been shown to be a determinant at the Xenopus gastrula organizer region and a segment-polarity determinant in Drosophila. In the present report, we present data on Goosecoid protein localization in staged mouse embryos. These data and the SAMS clinical phenotype both suggest that Goosecoid is a downstream effector of the regulatory networks that define neural-crest cell-fate specification and subsequent mesoderm cell lineages in mammals, particularly during shoulder and hip formation. Our findings confirm that Goosecoid has an essential role in human craniofacial and joint development and suggest that Goosecoid is an essential regulator of mesodermal patterning in mammals and that it has specific functions in neural crest cell derivatives. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  5. Inactivation of the Huntington's disease gene (Hdh impairs anterior streak formation and early patterning of the mouse embryo

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    Conlon Ronald A

    2005-08-01

    Full Text Available Abstract Background Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdhex4/5 huntingtin deficient embryos. Results In the absence of huntingtin, expression of nutritive genes appears normal but E7.0–7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE are specified. Conclusion Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in

  6. A Co-Association Network Analysis of the Genetic Determination of Pig Conformation, Growth and Fatness

    Science.gov (United States)

    Puig-Oliveras, Anna; Ballester, Maria; Corominas, Jordi; Revilla, Manuel; Estellé, Jordi; Fernández, Ana I.; Ramayo-Caldas, Yuliaxis; Folch, Josep M.

    2014-01-01

    Background Several QTLs have been identified for major economically relevant traits in livestock, such as growth and meat quality, revealing the complex genetic architecture of these traits. The use of network approaches considering the interactions of multiple molecules and traits provides useful insights into the molecular underpinnings of complex traits. Here, a network based methodology, named Association Weight Matrix, was applied to study gene interactions and pathways affecting pig conformation, growth and fatness traits. Results The co-association network analysis underpinned three transcription factors, PPARγ, ELF1, and PRDM16 involved in mesoderm tissue differentiation. Fifty-four genes in the network belonged to growth-related ontologies and 46 of them were common with a similar study for growth in cattle supporting our results. The functional analysis uncovered the lipid metabolism and the corticotrophin and gonadotrophin release hormone pathways among the most important pathways influencing these traits. Our results suggest that the genes and pathways here identified are important determining either the total body weight of the animal and the fat content. For instance, a switch in the mesoderm tissue differentiation may determinate the age-related preferred pathways being in the puberty stage those related with the miogenic and osteogenic lineages; on the contrary, in the maturity stage cells may be more prone to the adipocyte fate. Hence, our results demonstrate that an integrative genomic co-association analysis is a powerful approach for identifying new connections and interactions among genes. Conclusions This work provides insights about pathways and key regulators which may be important determining the animal growth, conformation and body proportions and fatness traits. Molecular information concerning genes and pathways here described may be crucial for the improvement of genetic breeding programs applied to pork meat production. PMID:25503799

  7. A co-association network analysis of the genetic determination of pig conformation, growth and fatness.

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    Anna Puig-Oliveras

    Full Text Available Several QTLs have been identified for major economically relevant traits in livestock, such as growth and meat quality, revealing the complex genetic architecture of these traits. The use of network approaches considering the interactions of multiple molecules and traits provides useful insights into the molecular underpinnings of complex traits. Here, a network based methodology, named Association Weight Matrix, was applied to study gene interactions and pathways affecting pig conformation, growth and fatness traits.The co-association network analysis underpinned three transcription factors, PPARγ, ELF1, and PRDM16 involved in mesoderm tissue differentiation. Fifty-four genes in the network belonged to growth-related ontologies and 46 of them were common with a similar study for growth in cattle supporting our results. The functional analysis uncovered the lipid metabolism and the corticotrophin and gonadotrophin release hormone pathways among the most important pathways influencing these traits. Our results suggest that the genes and pathways here identified are important determining either the total body weight of the animal and the fat content. For instance, a switch in the mesoderm tissue differentiation may determinate the age-related preferred pathways being in the puberty stage those related with the miogenic and osteogenic lineages; on the contrary, in the maturity stage cells may be more prone to the adipocyte fate. Hence, our results demonstrate that an integrative genomic co-association analysis is a powerful approach for identifying new connections and interactions among genes.This work provides insights about pathways and key regulators which may be important determining the animal growth, conformation and body proportions and fatness traits. Molecular information concerning genes and pathways here described may be crucial for the improvement of genetic breeding programs applied to pork meat production.

  8. Animal-vegetal asymmetries influence the earliest steps in retina fate commitment in Xenopus.

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    Moore, K B; Moody, S A

    1999-08-01

    An individual retina descends from a restricted and invariant group of nine animal blastomeres at the 32-cell stage. We tested which molecular signaling pathways are responsible for the competence of animal blastomeres to contribute to the retina. Inactivation of activin/Vg1 or fibroblast growth factor (FGF) signaling by expression of dominant-negative receptors does not prevent an animal blastomere from contributing to the retina. However, increasing bone morphogenetic protein (BMP) signaling in the retina-producing blastomeres significantly reduces their contribution. Conversely, reducing BMP signaling by expression of a dominant-negative BMP receptor or Noggin allows other animal blastomeres to contribute to the retina. Thus, the initial step in the retinal lineage is regulated by position within the BMP/Noggin field of epidermal versus neural induction. Vegetal tier blastomeres, in contrast, cannot contribute to the retina even when given access to the appropriate position and signaling fields by transplantation to the dorsal animal pole. We tested whether expression of molecules within the mesoderm inducing (activin, FGF), mesoderm-modifying (Wnt), or neural-inducing (BMP, Noggin) pathways impart a retinal fate on vegetal cell descendants. None of these, several of which induce secondary head structures, caused vegetal cells to contribute to retina. This was true even if the injected blastomeres were transplanted to the dorsal animal pole. Two pathways that specifically induce head tissues also were investigated. The simultaneous blockade of Wnt and BMP signaling, which results in the formation of a complete secondary axis with head and eyes, did not cause the vegetal clone to give rise to retina. However, Cerberus, a secreted protein that also induces an ectopic head with eyes, redirected vegetal progeny into the retina. These experiments indicate that vegetal blastomere incompetence to express a retinal fate is not due to a lack of components of known

  9. Expression of hLAMP-1-Positive Particles During Early Heart Development in the Chick.

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    Abd-Elhamid, T H; Conway, M L; Sinning, A R

    2017-10-01

    Heart development requires coordinated activity of various factors, the disturbance of which can lead to congenital heart defects. Heart lectin-associated matrix protein-1 (hLAMP-1) is a matrix protein expressed within Hensen's node at Hamburger-Hamilton (HH) stage 4, in the lateral mesoderm by HH stages 5-6 and enhanced within the left pre-cardiac field at HH stage 7. At HH stages 15-16, hLAMP-1 expression is observed in the atrioventricular canal and the outflow tract. Also, the role of hLAMP-1 in induction of mesenchyme formation in chick heart has been well documented. To further elucidate the role of this molecule in heart development, we examined its expression patterns during HH stages 8-14 in the chick. In this regard, we immunostained sections of the heart during HH stages 8-14 with antibodies specific to hLAMP-1. Our results showed prominent expression of hLAMP-1-positive particles in the extracellular matrix associated with the pre-cardiac mesoderm, the endoderm, ectoderm as well as neuroectoderm at HH stages 8-9. After formation of the linear heart tube at HH stage 10, the expression of hLAMP-1-stained particles disappears in those regions of original contact between the endoderm and heart forming fields due to rupture of the dorsal mesocardium while their expression becomes confined to the arterial and venous poles of the heart tube. This expression pattern is maintained until HH stage 14. This expression pattern suggests that hLAMP-1 may be involved in the formation of the endocardial tube. © 2017 Blackwell Verlag GmbH.

  10. Retinoic acid signalling in the zebrafish embryo is necessary during pre-segmentation stages to pattern the anterior-posterior axis of the CNS and to induce a pectoral fin bud.

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    Grandel, Heiner; Lun, Klaus; Rauch, Gerd-Jörg; Rhinn, Muriel; Piotrowski, Tatjana; Houart, Corinne; Sordino, Paolo; Küchler, Axel M; Schulte-Merker, Stefan; Geisler, Robert; Holder, Nigel; Wilson, Stephen W; Brand, Michael

    2002-06-01

    A number of studies have suggested that retinoic acid (RA) is an important signal for patterning the hindbrain, the branchial arches and the limb bud. Retinoic acid is thought to act on the posterior hindbrain and the limb buds at somitogenesis stages in chick and mouse embryos. Here we report a much earlier requirement for RA signalling during pre-segmentation stages for proper development of these structures in zebrafish. We present evidence that a RA signal is necessary during pre-segmentation stages for proper expression of the spinal cord markers hoxb5a and hoxb6b, suggesting an influence of RA on anteroposterior patterning of the neural plate posterior to the hindbrain. We report the identification and expression pattern of the zebrafish retinaldehyde dehydrogenase2 (raldh2/aldh1a2) gene. Raldh2 synthesises retinoic acid (RA) from its immediate precursor retinal. It is expressed in a highly ordered spatial and temporal fashion during gastrulation in the involuting mesoderm and during later embryogenesis in paraxial mesoderm, branchial arches, eyes and fin buds, suggesting the involvement of RA at different times of development in different functional contexts. Mapping of the raldh2 gene reveals close linkage to no-fin (nof), a newly discovered mutant lacking pectoral fins and cartilaginous gill arches. Cloning and functional tests of the wild-type and nof alleles of raldh2 reveal that nof is a raldh2 mutant. By treating nof mutants with RA during different time windows and by making use of a retinoic acid receptor antagonist, we show that RA signalling during pre-segmentation stages is necessary for anteroposterior patterning in the CNS and for fin induction to occur.

  11. Microarray analysis of Foxa2 mutant mouse embryos reveals novel gene expression and inductive roles for the gastrula organizer and its derivatives

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    Rossant Janet

    2008-10-01

    Full Text Available Abstract Background The Spemann/Mangold organizer is a transient tissue critical for patterning the gastrula stage vertebrate embryo and formation of the three germ layers. Despite its important role during development, there are still relatively few genes with specific expression in the organizer and its derivatives. Foxa2 is a forkhead transcription factor that is absolutely required for formation of the mammalian equivalent of the organizer, the node, the axial mesoderm and the definitive endoderm (DE. However, the targets of Foxa2 during embryogenesis, and the molecular impact of organizer loss on the gastrula embryo, have not been well defined. Results To identify genes specific to the Spemann/Mangold organizer, we performed a microarray-based screen that compared wild-type and Foxa2 mutant embryos at late gastrulation stage (E7.5. We could detect genes that were consistently down-regulated in replicate pools of mutant embryos versus wild-type, and these included a number of known node and DE markers. We selected 314 genes without previously published data at E7.5 and screened for expression by whole mount in situ hybridization. We identified 10 novel expression patterns in the node and 5 in the definitive endoderm. We also found significant reduction of markers expressed in secondary tissues that require interaction with the organizer and its derivatives, such as cardiac mesoderm, vasculature, primitive streak, and anterior neuroectoderm. Conclusion The genes identified in this screen represent novel Spemann/Mangold organizer genes as well as potential Foxa2 targets. Further investigation will be needed to define these genes as novel developmental regulatory factors involved in organizer formation and function. We have placed these genes in a Foxa2-dependent genetic regulatory network and we hypothesize how Foxa2 may regulate a molecular program of Spemann/Mangold organizer development. We have also shown how early loss of the organizer

  12. Multiple upstream modules regulate zebrafish myf5 expression

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    Weng Chih-Wei

    2007-01-01

    Full Text Available Abstract Background Myf5 is one member of the basic helix-loop-helix family of transcription factors, and it functions as a myogenic factor that is important for the specification and differentiation of muscle cells. The expression of myf5 is somite- and stage-dependent during embryogenesis through a delicate regulation. However, this complex regulatory mechanism of myf5 is not clearly understood. Results We isolated a 156-kb bacterial artificial chromosome clone that includes an upstream 80-kb region and a downstream 70-kb region of zebrafish myf5 and generated a transgenic line carrying this 156-kb segment fused to a green fluorescent protein (GFP reporter gene. We find strong GFP expression in the most rostral somite and in the presomitic mesoderm during segmentation stages, similar to endogenous myf5 expression. Later, the GFP signals persist in caudal somites near the tail bud but are down-regulated in the older, rostral somites. During the pharyngula period, we detect GFP signals in pectoral fin buds, dorsal rostral myotomes, hypaxial myotomes, and inferior oblique and superior oblique muscles, a pattern that also corresponds well with endogenous myf5 transcripts. To characterize the specific upstream cis-elements that regulate this complex and dynamic expression pattern, we also generated several transgenic lines that harbor various lengths within the upstream 80-kb segment. We find that (1 the -80 kb/-9977 segment contains a fin and cranial muscle element and a notochord repressor; (2 the -9977/-6213 segment contains a strong repressive element that does not include the notochord-specific repressor; (3 the -6212/-2938 segment contains tissue-specific elements for bone and spinal cord; (4 the -2937/-291 segment contains an eye enhancer, and the -2937/-2457 segment is required for notochord and myocyte expression; and (5 the -290/-1 segment is responsible for basal transcription in somites and the presomitic mesoderm. Conclusion We suggest

  13. Células-tronco mesenquimais Mesenchymal stem cell

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    Betânia Souza Monteiro

    2010-02-01

    Full Text Available Dentre todas as células-tronco estudadas até o presente momento, as mesenquimais (MSC destacam-se por sua elevada plasticidade, podendo originar tecidos mesodermais e não mesodermais. Além disso, possuem características imunomoduladoras e imunossupressoras que ampliam as possibilidades de utilização terapêutica. As MSC secretam uma grande variedade de citocinas pró e anti-inflamatórias e fatores de crescimento e, por meio dessas moléculas bioativas, proporcionam a modulação da resposta inflamatória, o restabelecimento do suprimento vascular e a reparação adequada do tecido, contribuindo para a homeostasia tissular e imunológica sob condições fisiológicas. Também podem induzir as demais células presentes no nicho tecidual a secretarem outros fatores solúveis que estimulam a diferenciação dessas células indiferenciadas, favorecendo o processo de reparação. A terapia celular com MSC é uma alternativa terapêutica promissora, porém a compreensão da biologia dessas células ainda é uma ciência em formação. Este artigo tem por objetivo realizar uma breve revisão sobre as células mesenquimais indiferenciadas.Of all the stem cells studied so far, the mesenchymal stem cells (MSC stand out for their high plasticity and capacity of generating mesodermal and non-mesodermal tissues. In addition, immunomodulatory and immunosuppressive features that expand possibilities for therapeutic use are present in these cells. A variety of pro and anti-inflammatory cytokines and growth factors are secrete for MSC and provide a modulation of inflammatory response, re-establishment of vascular supply and adequate repair of the tissue, contributing to tissue homeostasis under physiologic conditions. Therefore, they can induce secretion of soluble factors that stimulate their differentiation by other cells present at the niche's tissue, promoting the repair process. Cell therapy using MSC is a promises therapeutic alternative, but

  14. Hepatogenic and neurogenic differentiation of bone marrow mesenchymal stem cells from abattoir-derived bovine fetuses.

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    Dueñas, Fernando; Becerra, Víctor; Cortes, Yennifer; Vidal, Sonia; Sáenz, Leonardo; Palomino, Jaime; De Los Reyes, Mónica; Peralta, Oscar A

    2014-07-10

    Mesenchymal stem cells (MSC) are multipotent progenitor cells characterized by their ability to both self-renew and differentiate into tissues of mesodermal origin. The plasticity or transdifferentiation potential of MSC is not limited to mesodermal derivatives, since under appropriate cell culture conditions and stimulation by bioactive factors, MSC have also been differentiated into endodermal (hepatocytes) and neuroectodermal (neurons) cells. The potential of MSC for hepatogenic and neurogenic differentiation has been well documented in different animal models; however, few reports are currently available on large animal models. In the present study we sought to characterize the hepatogenic and neurogenic differentiation and multipotent potential of bovine MSC (bMSC) isolated from bone marrow (BM) of abattoir-derived fetuses. Plastic-adherent bMSC isolated from fetal BM maintained a fibroblast-like morphology under monolayer culture conditions. Flow cytometric analysis demonstrated that bMSC populations were positive for MSC markers CD29 and CD73 and pluripotency markers OCT4 and NANOG; whereas, were negative for hematopoietic markers CD34 and CD45. Levels of mRNA of hepatic genes α-fetoprotein (AFP), albumin (ALB), alpha1 antitrypsin (α1AT), connexin 32 (CNX32), tyrosine aminotransferase (TAT) and cytochrome P450 (CYP3A4) were up-regulated in bMSC during a 28-Day period of hepatogenic differentiation. Functional analyses in differentiated bMSC cultures evidenced an increase (P < 0.05) in albumin and urea production and glycogen storage. bMSC cultured under neurogenic conditions expressed NESTIN and MAP2 proteins at 24 h of culture; whereas, at 144 h also expressed TRKA and PrPC. Levels of MAP2 and TRKA mRNA were up-regulated at the end of the differentiation period. Conversely, bMSC expressed lower levels of NANOG mRNA during both hepatogenic and neurogenic differentiation processes. The expression patterns of linage-specific markers and the production of

  15. [Effects of cytosine-arabinofuranoside on the development of reptilian embryos (Lacerta viridis, Laur. and Anguis fragilis, L.)].

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    Raynaud, A

    1982-01-01

    Administered into the yolk sac of eggs of Lacerta viridis as a single dose of 17 to 40 micrograms, cytosine-arabinoside (Ara-C) was compatible with survival of the embryo, from the sixth day of incubation, for at least 20 to 25 days. The LD50 was 40 to 50 micrograms per egg. Doses of 20 to 40 micrograms of Ara-C introduced in the yolk sac of eggs of the slow-worm (Anguis fragilis) cultured in vitro, at stages of the allantoid bud of 0,5 mm to 2,5 mm long, killed the embryo in 4 to 8 days (possibly due to alterations of capillary blood vessels of allantois and area vasculosa). In the two species, these doses caused cytotoxic effects on embryonic proliferating tissues, growth inhibition and a variety of developmental defects. In young embryos of Anguis fragilis, similar doses of 20 to 40 micrograms of Ara-C caused, in 2 to 4 days, death of many cells in the anlagen of growing organs: neural tube, sensory organs, bronchi, mesoderm of the limb bud, subcutaneous mesenchyme, anlage of dorsal skeletal structures, etc.; followed by growth inhibition and malformations. On the other hand, in the limb bud, the apical ridge was less retrogressed than in control embryos; the limb buds showed slightly better development in treated embryos than in controls, but, Ara-C induced severe damage in their mesoderm. In all embryos of Lacerta viridis, treated at the stage of 6 days or of 10 days of incubation by doses of 20 to 40 micrograms of Ara-C and killed 15 to 35 days later, there was a general reduction of size and of weight and external and internal malformations, more or less severe, were present: modifications of the form of the head, shortening of the lower jaw, labial clefts, microphthalmia, micromelia and other limbs defects, developmental defects of the tail. In some embryos, the only external defects observed were missing fingers and toes; in three of these embryos, the same digits were missing in the four limbs. Modifications of limb morphogenesis induced by Ara-C are

  16. 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.

  17. Homothorax plays autonomous and nonautonomous roles in proximodistal axis formation and migration of the Drosophila renal tubules.

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    Zohar-Stoopel, Adi; Gonen, Nitzan; Mahroum, Mohammed; Ben-Zvi, Doreen S; Toledano, Hila; Salzberg, Adi

    2014-01-01

    The Drosophila Malpighian tubules (MpTs) serve as a functional equivalent of the mammalian renal tubules. The MpTs are composed of two pairs of epithelial tubes that bud from the midgut-hindgut boundary during embryogenesis. The MpT primordia grow, elongate and migrate through the body cavity to assume their final position and shape. The stereotypic pattern of MpT migration is regulated by multiple intrinsic and extrinsic signals, many of which are still obscure. In this work, we implicate the TALE-class homeoprotein Homothorax (Hth) in MpT patterning. We show that in the absence of Hth the tubules fail to rearrange and migrate. Hth plays both autonomous and nonautonomous roles in this developmental process. Within the tubules Hth is required for convergent extension and for defining distal versus proximal cell identities. The difference between distal and proximal cell identities seems to be required for proper formation of the leading loop. Outside the tubules, wide-range mesodermal expression of Hth is required for directing anterior migration. The nonautonomous effects of Hth on MpT migration can be partially attributed to its effects on homeotic determination along the anterior posterior axis of the embryo and to its effects on stellate cell (SC) incorporation into the MpT. Copyright © 2013 Wiley Periodicals, Inc.

  18. Induction and enhancement of cardiac cell differentiation from mouse and human induced pluripotent stem cells with cyclosporin-A.

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    Masataka Fujiwara

    Full Text Available Induced pluripotent stem cells (iPSCs are novel stem cells derived from adult mouse and human tissues by reprogramming. Elucidation of mechanisms and exploration of efficient methods for their differentiation to functional cardiomyocytes are essential for developing cardiac cell models and future regenerative therapies. We previously established a novel mouse embryonic stem cell (ESC and iPSC differentiation system in which cardiovascular cells can be systematically induced from Flk1(+ common progenitor cells, and identified highly cardiogenic progenitors as Flk1(+/CXCR4(+/VE-cadherin(- (FCV cells. We have also reported that cyclosporin-A (CSA drastically increases FCV progenitor and cardiomyocyte induction from mouse ESCs. Here, we combined these technologies and extended them to mouse and human iPSCs. Co-culture of purified mouse iPSC-derived Flk1(+ cells with OP9 stroma cells induced cardiomyocyte differentiation whilst addition of CSA to Flk1(+ cells dramatically increased both cardiomyocyte and FCV progenitor cell differentiation. Spontaneously beating colonies were obtained from human iPSCs by co-culture with END-2 visceral endoderm-like cells. Appearance of beating colonies from human iPSCs was increased approximately 4.3 times by addition of CSA at mesoderm stage. CSA-expanded human iPSC-derived cardiomyocytes showed various cardiac marker expressions, synchronized calcium transients, cardiomyocyte-like action potentials, pharmacological reactions, and ultra-structural features as cardiomyocytes. These results provide a technological basis to obtain functional cardiomyocytes from iPSCs.

  19. Development of the pericarp, septa and zone of dehiscence in the fruit of Cassia tora L.

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    K. S. Rao

    2014-01-01

    Full Text Available The pod of Cassia tora is the product of a single carpel consisting of 20-30 seeds enclosed one in each compartment formed by the ingrowth of the endocarpic tissue. There are three distinct histological zones of the pericarp Epicarp (a, Mesocarp (b and Endocarp (c. The paracytic stomata and uniseriate multicellular trichomes are found only in the outermost layer of the epicarp. The epicarp is single layered. The outer mesocarp in later stages of its development has many collenchyma, particularly at dorsal and ventral margins. The mesocarp develops from the homogenous mesodermal tissue of the ovary wall. The middle mesocarpic tissue becomes sclerenchymatous above the :main bundles providing rigidity at the two sutures where the zones of dehiscence develop inbetween them. The endocarp develops from the inner epidermis and 2-3 hypodermal layers. Due to frequent periclinal and anticlinal divisions and enlargement of the cells in the inner hypodermal layers, the septa are formed which never fuse; thus the so called compartment of the seed is not completely closed and the seeds slide off on separation of the valves. The inner hypodermal layers form the band of sclerenchyma above the septal cells. The inner margins without septa and sclerenchyma provide easy opening of the two valves from the chamber side.

  20. Targeted gene expression in transgenic Xenopus using the binary Gal4-UAS system.

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    Hartley, Katharine O; Nutt, Stephen L; Amaya, Enrique

    2002-02-05

    The transgenic technique in Xenopus allows one to misexpress genes in a temporally and spatially controlled manner. However, this system suffers from two experimental limitations. First, the restriction enzyme-mediated integration procedure relies on chromosomal damage, resulting in a percentage of embryos failing to develop normally. Second, every transgenic embryo has unique sites of integration and unique transgene copy number, resulting in variable transgene expression levels and variable phenotypes. For these reasons, we have adapted the Gal4-UAS method for targeted gene expression to Xenopus. This technique relies on the generation of transgenic lines that carry "activator" or "effector" constructs. Activator lines express the yeast transcription factor, Gal4, under the control of a desired promoter, whereas effector lines contain DNA-binding motifs for Gal4-(UAS) linked to the gene of interest. We show that on intercrossing of these lines, the effector gene is transcribed in the temporal and spatial manner of the activator's promoter. Furthermore, we use the Gal4-UAS system to misexpress Xvent-2, a transcriptional target of bone morphogenetic protein 4 (BMP4) signaling during early embryogenesis. Embryos inheriting both the Gal4 activator and Xvent-2 effector transgenes display a consistent microcephalic phenotype. Finally, we exploit this system to characterize the neural and mesodermal defects obtained from early misexpression of Xvent-2. These results emphasize the potential of this system for the controlled analyses of gene function in Xenopus.