In the developing muscle, a pool of myogenic progenitor cells is formed and maintained. These resident progenitors provide a source of undifferentiated cells for muscle growth in development and generate satellite cells in the perinatal period.
Recently, we could demonstrate that the transcription factor RBP-J, the major mediator of Notch signaling, is essential in keeping myogenic progenitor cells in an undifferentiated state. In the absence of RBP-J, progenitor cells undergo uncontrolled myogenic differentiation, resulting in a lack of muscle growth in development and severe muscle hypotrophy (Vasyutina 2007).
Skeletal muscle fibers are syncytia that arise by the fusion of myogenic cells. Mononucleated myogenic cells, the myoblasts, fuse with each other to form multinucleated myotubes. During development and in the adult, myoblast fusion allows generation, growth and repair of muscle fibers. Rac1 and Cdc42 are small G-proteins that regulate actin dynamics. We analyzed the function of Rac1 and Cdc42 in myogenesis using conditional mutagenesis in mice. We showed that in the absence of Rac1 and Cdc42, myoblast fusion is severely compromised in vivo and in vitro. The deficit in fusion of Rac1 or Cdc42 mutant myoblasts correlated with a deficit in the recruitment of actin fibers and vinculin to myoblast contact sites. Moreover, we demonstrated that Rac1 and Cdc42 are required in both fusion partners. Thus, our analysis demonstrated that the function of Rac1 is evolutionarily conserved from insects to mammals, and that Cdc42, a molecule hitherto not implicated in myoblast fusion, is essential for the fusion of murine myoblasts (Vasyutina 2009).