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.

骨骼肌纤维的形成是一个复杂的过程，由多种信号通路控制，包括 Wnt、Shh 和 FGF。然而，河马通路在脊椎动物肌纤维形成过程中的作用有相互矛盾的报道，我们决定在鸡肌肉培养中解决。我们发现转录调节因子 Yes 相关蛋白 (YAP) 高度集中在成肌细胞的细胞核内。随着细胞分化成肌管，YAP 定位转移到更成熟肌管中的细胞质。用 MST1/2 抑制剂 XMU-MP-1 (XMU) 处理培养物，刺激 YAP 在成肌细胞和肌管中的核定位，上调肌细胞生成素，促进成肌细胞融合，最终导致形成大的、完全横纹的多核细胞。肌管。