β-Catenin Regulates Myogenesis by Relieving I-mfa-Mediated Suppression of Myogenic Regulatory Factors in P19 Cells

Wnt/β-catenin signaling plays a critical role in embryonic myogenesis. Here we show that, in P19 embryonic carcinoma stem cells, Wnt/β-catenin signaling initiates the myogenic process depends on β-catenin-mediated relief of I-mfa (inhibitor of MyoD Family a) suppression of myogenic regulatory factors (MRFs). We found that β-catenin interacted with I-mfa and that the interaction was enhanced by Wnt3a. In addition, we found that the interaction between β-catenin and I-mfa was able to attenuate the interaction of I-mfa with MRFs, relieve I-mfa-mediated suppression of the transcriptional activity and cytosolic sequestration of MRFs, and initiate myogenesis in a P19 myogenic model system that expresses exogenous myogenin. This work reveals a mechanism for the regulation of MRFs during myogenesis by elucidating a β-catenin-mediated, but lymphoid enhancing factor-1/T cell factor independent, mechanism in regulation of myogenic fate specification and differentiation of P19 mouse stem cells.