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Serum Response Factor Controls Transcriptional Network Regulating Epidermal Function and Hair Follicle Morphogenesis.
MedLine Citation:
PMID:  23151848     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Serum response factor (SRF) is a transcription factor that regulates the expression of growth-related immediate-early, cytoskeletal, and muscle-specific genes to control growth, differentiation, and cytoskeletal integrity in different cell types. To investigate the role for SRF in epidermal development and homeostasis, we conditionally knocked out SRF in epidermal keratinocytes. We report that SRF deletion disrupted epidermal barrier function leading to early postnatal lethality. Mice lacking SRF in epidermis displayed morphogenetic defects, including an eye-open-at-birth phenotype and lack of whiskers. SRF-null skin exhibited abnormal morphology, hyperplasia, aberrant expression of differentiation markers and transcriptional regulators, anomalous actin organization, enhanced inflammation, and retarded hair follicle (HF) development. Transcriptional profiling experiments uncovered profound molecular changes in SRF-null E17.5 epidermis and revealed that many previously identified SRF target CArG box-containing genes were markedly upregulated in SRF-null epidermis, indicating that SRF may function to repress transcription of a subset of its target genes in epidermis. Remarkably, when transplanted onto nude mice, engrafted SRF-null skin lacked hair but displayed normal epidermal architecture with proper expression of differentiation markers, suggesting that although keratinocyte SRF is essential for HF development, a cross-talk between SRF-null keratinocytes and the surrounding microenvironment is likely responsible for the barrier-deficient mutant epidermal phenotype.Journal of Investigative Dermatology advance online publication, 15 November 2012; doi:10.1038/jid.2012.378.
Authors:
Congxing Lin; Anna Hindes; Carole J Burns; Aaron C Koppel; Alexi Kiss; Yan Yin; Liang Ma; Miroslav Blumenberg; Denis Khnykin; Frode L Jahnsen; Seth D Crosby; Narendrakumar Ramanan; Tatiana Efimova
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-15
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  -     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Division of Dermatology, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
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