Transcription factor families: Muscling in on the myogenic program

Embryonic skeletal muscle development has become a paradigm for understanding the molecular basis of how cell lineages are established and how cells differentiate into specialized structures. Most vertebrate muscles are derived from individual somites that produce two distinct muscle populations: the myotomal muscles that generate the axial and trunk musculature and a second migratory cell population that colonizes regions of the developing limbs. In both instances, muscle differentiation is accompanied by cell cycle arrest, fusion of individual myoblasts into multinucleate myotubes, and the transcriptional activation of muscle-specific genes. Recent experimental progress has led to greater understanding of the molecular mechanisms that control myogenesis in the embryo. Most of the advances have come from the identification and isolation of regulatory genes that are involved in controlling specific transcriptional events. In particular the muscle regulatory factor (MRF) and myocyte enhancer factor 2 (MEF2) families have been implicated in establishing the myogenic lineage as well as controlling terminal differentiation. Two additional transcription factors, Pax-3 and MLP, also appear to play a role in the production of a mature muscle cell. This review focuses on these four vertebrate transcription factor families and discusses the experimental evidence that these factors play important, non-overlapping roles in regulating skeletal muscle development.