Molecular mechanisms regulating myogenic determination and differentiation.

The myogenic regulatory factors are necessary for the determination and terminal differentiation of skeletal muscle. Gene targeting experiments have demonstrated that MyoD and Myf5 are important for myogenic determination whereas myogenin and MRF4 are important for terminal differentiation and lineage maintenance. During development, all trunk skeletal muscle is derived from the somite. Two spatially distinct sources of myogenic progenitors are defined by the expression of MyoD or Myf5 and these give rise to hypaxial and epaxial musculature. Both in vivo and in vitro analyses have provided a detailed picture regarding the molecular events controlling lineage determination, cell migration, terminal differentiation and tissue repair. Signal transduction pathways regulating cell cycle, protein-protein interactions and myogenic factor gene activation are implicated in the regulation of myogenesis. Recent experiments examining the origin and stem-cell capacity of satellite cells suggest that these cells may originate from the vascular system, are multipotential and may be useful for the treatment of several degenerative diseases.