Fig. 2. Epistatic relations among the myogenic bHLH factors. Shh and Wnt signaling from the notochord and dorsal neural tube, respectively, have been shown to regulate the expression of Myf5 in the epaxial dermamyotome of the somite (green). Pax3 and Myf5 independently regulate Myod expression. The factors regulating the early expression of Mrf4 are not known; however, it is likely that the same factors necessary for Myf5 expression regulate the transient expression of Mrf4 in the somite (shown as dashed lines) because these genes are physically very close together and share regulatory elements. Myod positively auto-regulates its own expression and activates the expression of Myog, and both Myod and Myog are expressed during skeletal muscle differentiation. In addition to its early and transient expression in the somite, Mrf4 is also expressed in the terminally differentiated muscle cells, and it is likely that Myod and Myog regulate this late expression of Mrf4. A transgene that drives Mrf4 expression from the Myog promoter can partly compensate for the loss of Myog (Zhu and Miller, 1997), demonstrating a partly redundant role of Mrf4 and Myog in terminal differentiation.