MYF5

Myf5, also known as myogenic factor 5, is a member of the myogenic regulatory factor (MRF) family of basic helix-loop-helix transcription factors that drive skeletal muscle formation. Along with MyoD, MRF4 (Myf6), and myogenin, Myf5 acts as a master regulator of myogenesis, initiating the genetic program that leads a cell to become skeletal muscle.

In vertebrate development, Myf5 is expressed in the presomitic mesoderm and early somites, marking the specification of myogenic progenitors. It forms heterodimers with E proteins and binds E-box DNA motifs to activate muscle-specific genes, promoting myoblast formation and differentiation. Genetic studies in mice show that loss of Myf5 reduces or delays skeletal muscle development; removal of both Myf5 and MyoD abolishes most skeletal muscle, illustrating partial redundancy among MRFs.

In the adult, Myf5 is transiently re-expressed in or around satellite cells during muscle regeneration and contributes to the specification of muscle-repairing progenitors. The Myf5-expressing lineage represents one subset of the myogenic precursors, with other cells relying on MyoD or other MRFs.

Myf5 is evolutionarily conserved across vertebrates and is typically around 25 kDa. It is regulated by signaling pathways such as Wnt and Sonic hedgehog during development, and its activity is intertwined with other MRFs to coordinate the myogenic program. Abnormal regulation of MRF pathways can contribute to congenital muscle defects, though direct human disease associations with MYF5 mutations are rare.