Abstract
BackgroundAdult skeletal muscle regeneration is a highly orchestrated process involving the activation and proliferation of satellite cells, an adult skeletal muscle stem cell. Activated satellite cells generate a transient amplifying progenitor pool of myoblasts that commit to differentiation and fuse into multinucleated myotubes. During regeneration, canonical Wnt signalling is activated and has been implicated in regulating myogenic lineage progression and terminal differentiation.MethodsHere, we have undertaken a gene expression analysis of committed satellite cell-derived myoblasts to examine their ability to respond to canonical Wnt/β-catenin signalling.ResultsWe found that activation of canonical Wnt signalling induces follistatin expression in myoblasts and promotes myoblast fusion in a follistatin-dependent manner. In growth conditions, canonical Wnt/β-catenin signalling prime myoblasts for myogenic differentiation by stimulating myogenin and follistatin expression. We further found that myogenin binds elements in the follistatin promoter and thus acts downstream of myogenin during differentiation. Finally, ectopic activation of canonical Wnt signalling in vivo promoted premature differentiation during muscle regeneration following acute injury.ConclusionsTogether, these data reveal a novel mechanism by which myogenin mediates the canonical Wnt/β-catenin-dependent activation of follistatin and induction of the myogenic differentiation process.Electronic supplementary materialThe online version of this article (doi:10.1186/s13395-015-0038-6) contains supplementary material, which is available to authorized users.
Highlights
Adult skeletal muscle regeneration is a highly orchestrated process involving the activation and proliferation of satellite cells, an adult skeletal muscle stem cell
To further investigate the role of canonical Wnt signalling in adult myogenesis, we analyzed the response of satellite cell-derived myoblasts to Wnt/β-catenin signalling
To further investigate the role of canonical Wnt signalling in adult myogenesis, we analyzed the response of satellite cell-derived myoblasts to Wnt/β-catenin signalling by genome-wide microarray expression analysis
Summary
Adult skeletal muscle regeneration is a highly orchestrated process involving the activation and proliferation of satellite cells, an adult skeletal muscle stem cell. Canonical Wnt signalling is activated and has been implicated in regulating myogenic lineage progression and terminal differentiation. Satellite cells activate, proliferate, and differentiate into new myofibers or fuse to existing myofibers. Skeletal muscle regeneration is a highly orchestrated process contingent upon the proper expression of the paired-box transcription factor Pax, and the basic helix-loop-helix (bHLH) myogenic regulatory factors (MRFs); Myf, MyoD, myogenin, and MRF4. Myf and MyoD function to specify myogenic identity in proliferating myoblasts, whereas myogenin and MRF4 are upregulated during differentiation to trigger the expression of myogenic differentiation-specific genes [6]. We have previously shown that the symmetric expansion of satellite stem cells and their
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
