We have continued our studies on the genes involved in cellular commitment and differentiation during myogenesis. In addition to the expression of the structural genes characteristic of differentiated muscle, myogenesis involves the interaction of four myogenic determination genes in the vertebrates, MyoD, myogenin, Myf 5, and MRF4, the MyoD family of myogenic regulators. These genes are thought to play a role in muscle cell commitment in the somites as well as the transcriptional regulation of the muscle structural genes during differentiation. We have isolated all four of these genes from the chicken and have focused most of our attention on the avian MyoD homolog, CMD1, since it is expressed in the somites, the myoblast, and in the newly differentiated muscle fiber. These myogenic regulatory factors are phosphorylated and bind to their target sequences as dimers. We have analyzed the role of phosphorylation and the nature of the dimer (either homo or heterodimer) in CMD1 function. In the latter case, this has led to the characterization of at least two and possibly three proteins involved in heterodimer formation in myoblasts and fibers that may modulate CMD1 function. In order to take a genetic approach to the study of myogenesis, we have isolated the MyoD homolog from Drosophila, called Dmyd or nau. Dmyd is the only MyoD homolog in Drosophila, it is transiently expressed in a subset of muscle precursor cells in a segment specific pattern, and the majority of larval muscles contain at least one Dmyd positive cell. By studying the upstream and downstream genes in the myogenic pathway in Drosophila we hope to identify correlates in the vertebrates.
