Muscle stem cells in developmental and regenerative myogenesis

Abstract

Skeletal muscle development serves as a paradigm for cell lineage specification and cell differentiation. Adult skeletal muscle has high regenerative capacity, with satellite cells the primary source of this capability. The present review describes recent findings on developmental and adult myogenesis with emphasis on emerging distinctions between various muscle groups and stages of myogenesis. Muscle progenitors of the body are derived from multipotent cells of the dermomyotome and express the transcription factors Pax3 and Pax7. These cells self-renew or induce expression of myogenic regulatory factors (MRFs) and differentiate. The roles of Pax3, Pax7 and specific myogenic regulatory factor progenitor populations in trunk and limb myogenesis have been identified through cell ablation in the mouse. Various head muscles and associated satellite cells have differing developmental origins, and rely on distinct combinations of transcriptional regulators, than trunk and limb muscles. Several genetic and sorting protocols demonstrate that satellite cells are heterogeneous with some possessing stem cell properties; the relative roles of lineage and niche in these properties are being explored. Although cellular mechanisms of developmental, postnatal and adult regenerative myogenesis are thought to be similar, recent studies reveal distinct genetic requirements for embryonic, fetal, postnatal and adult regenerative myogenesis. Genetic determinants of formation or repair of various muscles during different stages of myogenesis are unexpectedly diverse. Future studies should illuminate these differences, as well as mechanisms that underlie stem cell properties of satellite cells.