The temporal specific role of WNT/β-catenin signaling during myogenesis.

Disruption of WNT/β-catenin signaling causes muscle developmental defects. However, it has been unclear how WNT/β-catenin signaling regulates each step of myogenesis. The in vitro culture of primary myoblasts and C2C12 cells (a myoblast cell line) has the ability to differentiate into myofibers in culture with differentiation inducers. These in vitro systems are useful to investigate each step of muscle development, ranging from cell proliferation to homeostasis, under the control of experimental conditions. Our recent study shows that WNT/β-catenin signaling can regulate myogenesis in a temporal specific manner by controlling the gene expression of cyclin A2 (Ccna2) and cell division cycle 25C (Cdc25c) during myoblast proliferation and fermitin family homolog 2 (Fermt2) during myoblast fusion and differentiation, respectively. In the well-differentiated myofibers, WNT/β-catenin signaling plays a role in the maintenance of their structure through a cadherin/β-catenin/actin complex formation, which is important for connecting a myofiber's cytoskeleton to the surrounding extracellular matrix. Thus, our recent study coupled with previous findings indicates that WNT/β-catenin signaling regulates myogenesis in a variety of ways, and any failure of these steps of myogenesis causes muscle developmental defects.