We have isolated and characterized a number of muscle-specific as well as generally expressed cellular genes that are differentially regulated during muscle formation (myogenesis) in vitro. These include the muscle-specific genes for alpha cardiac actin, alpha skeletal actin, the myosin light chains 1f/3f, and the ubiquitously expressed beta actin gene. Through deletion and transfection analyses, we have been able to define minimal cis-acting regions responsible for developmental regulation of these genes in a muscle cell background. In addition to a variety of generic transcription factors, the muscle-specific genes require the presence of additional muscle-specific factors, the MyoD family of proteins, which are required not only for specific muscle transcription but also for cellular determination of the muscle phenotype. We have since focused out studies on the mechanism of action of two of the four MyoD-like genes isolated in the vertebrates: the avian MyoD, called CMD1, and the avian myogenin, called Cmgn. We have also isolated the single homologue to the vertebrate genes from Drosophila, called Dmyd (Drosophila myogenic determination factor), in order to study the function of these genes genetically and biochemically. Such an approach should enable us to study the upstream and downstream genes in the myogenic determination pathway and to look for correlates in the vertebrate system.
NIH ExPorter
NIH ExPorter