Reciprocal inhibition between Pax7 and muscle regulatory factors modulates myogenic cell fate determination.

Postnatal growth and regeneration of skeletal muscle requires a population of resident myogenic precursors named satellite cells. The transcription factor Pax7 is critical for satellite cell biogenesis and survival and has been also implicated in satellite cell self-renewal; however, the underlying molecular mechanisms remain unclear. Previously, we showed that Pax7 overexpression in adult primary myoblasts down-regulates MyoD and prevents myogenin induction, inhibiting myogenesis. We show that Pax7 prevents muscle differentiation independently of its transcriptional activity, affecting MyoD function. Conversely, myogenin directly affects Pax7 expression and may be critical for Pax7 down-regulation in differentiating cells. Our results provide evidence for a cross-inhibitory interaction between Pax7 and members of the muscle regulatory factor family. This could represent an additional mechanism for the control of satellite cell fate decisions resulting in proliferation, differentiation, and self-renewal, necessary for skeletal muscle maintenance and repair.

Hedgehog acts directly on the zebrafish dermomyotome to promote myogenic differentiation.

Vertebrate myogenesis is regulated by signaling proteins secreted from surrounding tissues. One of the most important, Sonic hedgehog, has been proposed to regulate myogenic precursor cell survival, proliferation, and differentiation in a variety of vertebrates. In zebrafish, Hedgehog signaling is both necessary and sufficient for the development of embryonic slow muscle fibers-the earliest differentiating muscle fibers. Here we investigated the function of Hedgehog signaling in another zebrafish myogenic lineage, a dermomyotomal population of cells defined by somitic pax3/7 expression. We found that Hedgehog negatively regulates the number of myogenic precursors expressing pax3/7. Hh also positively regulates the growth of embryonic fast muscle. Unlike Hedgehog's function in regulating the elongation of fast muscle fibers, this regulation is not mediated by embryonic slow muscle fibers. Instead, it is a direct Hedgehog response, cell autonomous to myogenic precursors. The regulation of myogenic precursors and their differentiation into fast fibers have a different critical time period for Hh signaling, and different requirements for specific gli gene family members of Hh activated transcription factors from the earlier promotion of embryonic slow muscle fiber differentiation. We propose that Hedgehog signaling acts at multiple times on different lineages, through different downstream pathways, to promote myogenic differentiation.