Looking back to the embryo: defining transcriptional networks in adult myogenesis

Abstract

In response to muscle damage, specialized adult myogenic progenitors known as satellite cells activate a myogenic transcriptional programme, which is analogous to that induced during embryonic and fetal muscle development. Either MyoD or Myf5 is required for the commitment of skeletal myogenic cells; in the absence of both transcription factors, progenitor cells assume non-muscle fates. Pax3 and Myf5 function upstream of MyoD in embryonic myogenesis. Pax3 is required for the proliferation, survival and specification of stem cells in the pre-somitic mesoderm. Shh directly activates Myf5 transcription through specific Gli1 binding sites in the epaxial somite enhancer. Activation of several signalling pathways — including the Wnt, Hedgehog, BMP and Notch cascades — determines the balance between the determination, proliferation, survival and differentiation of muscle progenitors in the somite. Pax7 is required for the development of adult muscle satellite cells that function in the postnatal growth and repair of skeletal muscle fibers. MyoD is required for adult muscle regeneration by promoting the myogenic differentiation of satellite-cell derived myoblasts. The activation or modulation of signalling pathways that are implicated in embryonic and fetal muscle formation might provide a useful therapeutic strategy for the generation of muscle cells from adult stem cells either in vivo or ex vivo.