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First published online 8 April 2008
doi: 10.1242/jcs.024885

Journal of Cell Science 121, 1373-1382 (2008)
Published by The Company of Biologists 2008
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Research Article

β-catenin promotes self-renewal of skeletal-muscle satellite cells

Ana Perez-Ruiz1, Yusuke Ono1, Viola F. Gnocchi1,2 and Peter S. Zammit1,*

1 King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, London, SE1 1UL, UK
2 Department of Medical Sciences, University of Piemonte Orientale "Amedeo Avogadro", Novara, Italy

* Author for correspondence (e-mail: peter.zammit{at}kcl.ac.uk)

Accepted 26 January 2008

Satellite cells are the resident stem cells of adult skeletal muscle. As with all stem cells, how the choice between self-renewal or differentiation is controlled is central to understanding their function. Here, we have explored the role of β-catenin in determining the fate of myogenic satellite cells. Satellite cells express β-catenin, and expression is maintained as they activate and undergo proliferation. Constitutive retroviral-driven expression of wild-type or stabilised β-catenin results in more satellite cells expressing Pax7 without any MyoD – therefore, adopting the self-renewal pathway, with fewer cells undergoing myogenic differentiation. Similarly, preventing the degradation of endogenous β-catenin by inhibiting GSK3β activity also results in more Pax7-positive–MyoD-negative (Pax7+MyoD–) satellite-cell progeny. Consistent with these observations, downregulation of β-catenin using small interfering RNA (siRNA) reduced the proportion of satellite cells that express Pax7 and augmented myogenic differentiation after mitogen withdrawal. Since a dominant-negative version of β-catenin had the same effect as silencing β-catenin using specific siRNA, β-catenin promotes self-renewal via transcriptional control of target genes. Thus, β-catenin signalling in proliferating satellite cells directs these cells towards the self-renewal pathway and, so, contributes to the maintenance of this stem-cell pool in adult skeletal muscle.

Key words: Satellite cell, Stem cell, Skeletal muscle, β-catenin, Pax7, MyoD, Cell fate, Self-renewal




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J. Cell Sci., September 15, 2008; 121(18): 2975 - 2982.
[Abstract] [Full Text] [PDF]


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