Document Detail


WNT5A/JNK and FGF/MAPK pathways regulate the cellular events shaping the vertebrate limb bud.
MedLine Citation:
PMID:  21055947     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The vertebrate limb is a classical model for understanding patterning of three-dimensional structures during embryonic development. Although decades of research have elucidated the tissue and molecular interactions within the limb bud required for patterning and morphogenesis of the limb, the cellular and molecular events that shape the limb bud itself have remained largely unknown.
RESULTS: We show that the mesenchymal cells of the early limb bud are not disorganized within the ectoderm as previously thought but are instead highly organized and polarized. Using time-lapse video microscopy, we demonstrate that cells move and divide according to this orientation. The combination of oriented cell divisions and movements drives the proximal-distal elongation of the limb bud necessary to set the stage for subsequent morphogenesis. These cellular events are regulated by the combined activities of the WNT and FGF pathways. We show that WNT5A/JNK is necessary for the proper orientation of cell movements and cell division. In contrast, the FGF/MAPK signaling pathway, emanating from the apical ectodermal ridge, does not regulate cell orientation in the limb bud but instead establishes a gradient of cell velocity enabling continuous rearrangement of the cells at the distal tip of the limb.
CONCLUSIONS: Together, these data shed light on the cellular basis of vertebrate limb bud morphogenesis and uncover new layers to the sequential signaling pathways acting during vertebrate limb development.
Authors:
Jerome Gros; Jimmy Kuang-Hsien Hu; Claudio Vinegoni; Paolo Fumene Feruglio; Ralph Weissleder; Clifford J Tabin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-11-04
Journal Detail:
Title:  Current biology : CB     Volume:  20     ISSN:  1879-0445     ISO Abbreviation:  Curr. Biol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-04-18     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  9107782     Medline TA:  Curr Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1993-2002     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Genetics, Harvard Medical School, and Center for Systems Biology, Massachusetts General Hospital, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Patterning / genetics
Cell Movement
Chick Embryo
Embryo, Mammalian / metabolism
Embryonic Development / genetics
Female
Fibroblast Growth Factors / metabolism,  physiology*
JNK Mitogen-Activated Protein Kinases / metabolism,  physiology*
Limb Buds / cytology,  embryology*,  metabolism
MAP Kinase Signaling System*
Mice
Morphogenesis / genetics
Wnt Proteins / genetics,  metabolism,  physiology*
Grant Support
ID/Acronym/Agency:
P01-AI05490/AI/NIAID NIH HHS; R01 HD045499/HD/NICHD NIH HHS; R01 HD045499-07/HD/NICHD NIH HHS; R01 HD045499-08/HD/NICHD NIH HHS; R01-EB006432/EB/NIBIB NIH HHS; R01-HD045499/HD/NICHD NIH HHS; R37 HD032443/HD/NICHD NIH HHS; UO1-HL080731/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Wnt Proteins; 0/Wnt5a protein, mouse; 62031-54-3/Fibroblast Growth Factors; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases
Comments/Corrections
Comment In:
Curr Biol. 2011 Jan 11;21(1):R34-6   [PMID:  21215936 ]

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