Document Detail


Sonic hedgehog-dependent activation of Gli2 is essential for embryonic hair follicle development.
MedLine Citation:
PMID:  12533516     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Sonic hedgehog (Shh) signaling plays a critical role in hair follicle development and skin cancer, but how it controls these processes remains unclear. Of the three Gli transcription factors involved in transducing Shh signals in vertebrates, we demonstrate here that Gli2 is the key mediator of Shh responses in skin. Similar to Shh(-/-) mice, Gli2(-/-) mutants exhibit an arrest in hair follicle development with reduced cell proliferation and Shh-responsive gene expression, but grossly normal epidermal differentiation. By transgenic rescue experiments, we show that epidermal Gli2 function alone is sufficient to restore hair follicle development in Gli2(-/-) skin. Furthermore, only a constitutively active form of Gli2, but not wild-type Gli2, can activate Shh-responsive gene expression and promote cell proliferation in Shh(-/-) skin. These observations indicate that Shh-dependent Gli2 activator function in the epidermis is essential for hair follicle development. Our data also reveal that Gli2 mediates the mitogenic effects of Shh by transcriptional activation of cyclin D1 and cyclin D2 in the developing hair follicles. Together, our results suggest that Shh-dependent Gli2 activation plays a critical role in epithelial homeostasis by promoting proliferation through the transcriptional control of cell cycle regulators.
Authors:
Pleasantine Mill; Rong Mo; Hong Fu; Marina Grachtchouk; Peter C W Kim; Andrzej A Dlugosz; Chi-chung Hui
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Genes & development     Volume:  17     ISSN:  0890-9369     ISO Abbreviation:  Genes Dev.     Publication Date:  2003 Jan 
Date Detail:
Created Date:  2003-01-20     Completed Date:  2003-02-13     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  282-94     Citation Subset:  IM    
Affiliation:
Program in Developmental Biology, The Hospital for Sick Children, and Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation
Cell Division
Gene Expression Regulation, Developmental
Hair Follicle / embryology*
Hedgehog Proteins
Kruppel-Like Transcription Factors
Mice
Mice, Knockout
Mice, Transgenic
Skin / cytology,  embryology
Trans-Activators / deficiency,  genetics,  physiology*
Transcription Factors / deficiency,  genetics,  physiology*
Grant Support
ID/Acronym/Agency:
R01 AR45973/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Gli2 protein; 0/Hedgehog Proteins; 0/Kruppel-Like Transcription Factors; 0/Shh protein, mouse; 0/Trans-Activators; 0/Transcription Factors
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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