Canonical Wnt/β-catenin signaling plays an important role in myogenic differentiation, but its physiological role in muscle fibers remains elusive. Here, we studied activation of Wnt/β-catenin signaling in adult muscle fibers and muscle stem cells in an Axin2 reporter mouse. Axin2 is a negative regulator and a target of Wnt/β-catenin signaling. In adult muscle fibers, Wnt/β-catenin signaling is only detectable in a subset of fast fibers that have a significantly smaller diameter than other fast fibers. In the same fibers, immunofluorescence staining for YAP/Taz and Tead1 was detected. Wnt/β-catenin signaling was absent in quiescent and activated satellite cells. Upon injury, Wnt/β-catenin signaling was detected in muscle fibers with centrally located nuclei. During differentiation of myoblasts expression of Axin2, but not of Axin1, increased together with Tead1 target gene expression. Furthermore, absence of Axin1 and Axin2 interfered with myoblast proliferation and myotube formation, respectively. Treatment with the canonical Wnt3a ligand also inhibited myotube formation. Wnt3a activated TOPflash and Tead1 reporter activity, whereas neither reporter was activated in the presence of Dkk1, an inhibitor of canonical Wnt signaling. We propose that Axin2-dependent Wnt/β-catenin signaling is involved in myotube formation and, together with YAP/Taz/Tead1, associated with reduced muscle fiber diameter of a subset of fast fibers.
The authors declare no competing or financial interests.
Conceptualization: S.H., J.v.M., J.B.; Methodology: D.H., N.E., M.R., L.M.Z., B.K.; Investigation: D.H., N.E., M.R., L.M.Z., B.K., D.B.; Resources: D.B.; Writing – original draft preparation: S.H.; Writing – review and editing: S.H., J.v.M., J.B., D.H.; Supervision: S.H., J.v.M., J.B.; Project administration: S.H.; Funding acquisition: S.H., J.v.M., J.B.
This work was supported by a grant from the German Research Foundation (Deutsche Forschungsgemeinschaft) [MA-3975/2-1] to J.v.M.; the Emerging Fields Initiative (EFI) of Friedrich-Alexander-Universität Erlangen-Nürnberg to J.B.; and the Interdisciplinary Center for Clinical Research Erlangen, at Universitätsklinikum Erlangen-Nürnberg project E17 to S.H.
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.139907.supplemental
- Received May 22, 2016.
- Accepted July 13, 2016.