Activation of YAP regulates muscle fiber size in a PKC-dependent mechanism during chick in vitro myogenesis

The formation of skeletal muscle fibers is an intricate process controlled by a multitude of signaling pathways, including Wnt, Shh, and FGF. However, the role of the Hippo pathway during vertebrate myofiber formation has conflicting reports, which we decided to address in chick muscle cultures. We found that the transcriptional regulator Yes-associated protein (YAP) was highly concentrated within the nuclei of myoblasts. As cells differentiate into myotubes, YAP localization shifted to the cell cytoplasm in more mature myotubes. Treatment of cultures with XMU-MP-1 (XMU), a MST1/2 inhibitor, stimulated the nuclear localization of YAP in myoblasts and in myotubes, upregulated myogenin, and promoted myoblast fusion, ultimately resulting in the formation of large and fully striated multinucleated myotubes. The XMU-induced phenotype was blocked by the protein kinase C (PKC) inhibitor calphostin, which raises the possibility that the Hippo pathway controls the growth of skeletal muscle fibers through a PKC-dependent mechanism.

Automated summary

The Hippo pathway plays a role in regulating the growth of skeletal muscle fibers through a PKC-dependent mechanism. YAP is highly concentrated in the nuclei of myoblasts and shifts to the cytoplasm as cells differentiate into myotubes. Treatment with XMU promotes myogenin expression and myoblast fusion, resulting in the formation of large multinucleated myotubes.