Satellite cells are main muscle stem cells that could provide myonuclei for myofiber growth and synaptic-specific gene expression during the early postnatal development. Here, we observed that splicing factor SRSF1 is highly expressed in myoblasts and its expression is closely related with satellite cell activation and proliferation. By genetic deletion of SRSF1 in myogenic progenitors, we found that SRSF1 is critical for satellite cell proliferation in vitro and in vivo. Most notably we also observed that SRSF1 is required for the functional neuromuscular junction (NMJ) formation, as SRSF1-deficient mice fail to form mature pretzel-like NMJs, which leads to muscle weakness and premature death in mice. Finally, we demonstrated that SRSF1 contributes to muscle innervation and muscle development likely by regulating a restricted set of tissue-specific alternative splicing events. Thus, our data define a unique role for SRSF1 in postnatal skeletal muscle growth and function in mice.

卫星细胞是主要的肌肉干细胞，可在产后早期发育期间为肌纤维生长和突触特异性基因表达提供肌核。在这里，我们观察到剪接因子SRSF1在成肌细胞中高度表达，其表达与卫星细胞的活化和增殖密切相关。通过在成肌祖细胞中遗传删除SRSF1，我们发现SRSF1对于体外和体内卫星细胞增殖至关重要。最值得注意的是，我们还观察到功能性神经肌肉接头（NMJ）形成需要SRSF1，因为缺乏SRSF1的小鼠无法形成成熟的椒盐卷饼样NMJ，从而导致小鼠肌肉无力和过早死亡。最后，我们证明了SRSF1可能通过调节一组受限的组织特异性替代剪接事件来促进肌肉神经支配和肌肉发育。因此，我们的数据定义了SRSF1在小鼠出生后骨骼肌生长和功能中的独特作用。