DETERMINATION VERSUS DIFFERENTIATION AND THE MYOD FAMILY OF TRANSCRIPTION FACTORS

The myogenic regulatory factors (MRFs) form a family of basic helix-lo op-helix transcription factors consisting of Myf-5, MyoD, myogenin, an d MRF4. The MRFs play key regulatory roles in the development of skele tal muscle during embryogenesis. Sequence homology, expression pattern s, and gene-targeting experiments have revealed a two-tiered subclassi fication within the MRF family. Myf-5 and MyoD are more homologous to one another than to the others, are expressed in myoblasts before diff erentiation, and are required for the determination or survival of mus cle progenitor cells. By contrast, myogenin and MRF4 are more homologo us to one another than to the others and are expressed upon differenti ation, and myogenin is required in vivo as a differentiation factor wh ile the role of MRF4 remains unclear. On this basis, MyoD and Myf-5 ar e classified as primary MRFs, as they are required for the determinati on of myoblasts, and myogenin and MRF4 are classified as secondary MRF s, as they likely function during terminal differentiation.