Integrated functions of Pax3 and Pax7 in the regulation of proliferation, cell size and myogenic differentiation

This study investigates the roles of the transcription factors Pax3 and Pax7 in adult muscle progenitor cells (satellite cell–derived myoblasts). Using gain- and loss-of-function approaches in C2C12 cells and primary satellite cells, the authors show that both Pax3 and Pax7 promote myoblast proliferation and reduce cell size, thereby supporting expansion of the muscle precursor pool. Constitutive expression of either factor does not block differentiation but results in the formation of thinner myotubes, whereas dominant-negative inhibition of Pax3 or Pax7 prevents myogenic differentiation, suppresses expression of key myogenic regulators (Myf5, MyoD, and myogenin), and disrupts myotube formation. The authors conclude that Pax3 and Pax7 have overlapping functions in adult myogenesis: they drive proliferation and maintain myogenic gene expression while keeping cells poised to differentiate in response to appropriate cues, a balance that is essential for effective muscle regeneration and tissue maintenance.