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The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells
Robert N. Judson, Annie M. Tremblay, Paul Knopp, Robert B. White, Roby Urcia, Cosimo De Bari, Peter S. Zammit, Fernando D. Camargo, Henning Wackerhage


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.


  • Funding

    This research was funded by an Oliver Bird PhD studentship to R.J.; a Medical Research Council project grant [grant number 99477 to H.W., P.S.Z., C.D.B.]; and by a grant by Tenovus Scotland [grant number G11/05 to C.D.B., H.W.]; P.K. was supported by a Medical Research Council Doctorial training grant awarded to King's College London; A.M.T. is recipient of a postdoctoral fellowship from the Canadian Institutes of Health Research (CIHR); R.B.W. was funded by the Wellcome Trust [grant number 085137/Z/08/Z] and the Raine Medical Research Foundation. Microarray studies were performed by the Molecular Genetics Core Facility at Children's Hospital Boston supported by National Institutes of Health [grant numbers NIH-P50-NS40828, NIH-P30-HD18655]. Deposited in PMC for release after 6 months.

  • Supplementary material available online at

  • Accepted September 5, 2012.
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