Document Detail

The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells.
MedLine Citation:
PMID:  23038772     Owner:  NLM     Status:  MEDLINE    
Satellite cells are the resident stem cells of skeletal muscle. Mitotically quiescent in mature muscle, they can be activated to proliferate and generate myoblasts to supply further myonuclei to hypertrophying or regenerating muscle fibres, or self-renew to maintain the resident stem cell pool. Here, we identify the transcriptional co-factor Yap as a novel regulator of satellite cell fate decisions. Yap expression increases during satellite cell activation and Yap remains highly expressed until after the differentiation versus self-renewal decision is made. Constitutive expression of Yap maintains Pax7(+) and MyoD(+) satellite cells and satellite cell-derived myoblasts, promotes proliferation but prevents differentiation. In contrast, Yap knockdown reduces the proliferation of satellite cell-derived myoblasts by ≈40%. Consistent with the cellular phenotype, microarrays show that Yap increases expression of genes associated with Yap inhibition, the cell cycle, ribosome biogenesis and that it represses several genes associated with angiotensin signalling. We also identify known regulators of satellite cell function such as BMP4, CD34 and Myf6 (Mrf4) as genes whose expression is dependent on Yap activity. Finally, we confirm in myoblasts that Yap binds to Tead transcription factors and co-activates MCAT elements which are enriched in the proximal promoters of Yap-responsive genes.
Robert N Judson; Annie M Tremblay; Paul Knopp; Robert B White; Roby Urcia; Cosimo De Bari; Peter S Zammit; Fernando D Camargo; Henning Wackerhage
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-04
Journal Detail:
Title:  Journal of cell science     Volume:  125     ISSN:  1477-9137     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2013-02-28     Completed Date:  2014-01-29     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  6009-19     Citation Subset:  IM    
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MeSH Terms
Adaptor Proteins, Signal Transducing / genetics,  metabolism*
Cell Growth Processes / physiology
Cell Nucleus / metabolism
Chick Embryo
Phosphoproteins / genetics,  metabolism*
Protein-Serine-Threonine Kinases / metabolism*
Satellite Cells, Skeletal Muscle / cytology*,  metabolism*
Signal Transduction
Grant Support
085137/Z/08/Z]//Wellcome Trust; 99477//Medical Research Council; G1100193//Medical Research Council; P30-HD18655/HD/NICHD NIH HHS; P50-NS40828/NS/NINDS NIH HHS; //Canadian Institutes of Health Research
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Phosphoproteins; 0/Yap protein, mouse; EC protein, mouse; EC Kinases

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