Molecular mechanisms of myogenesis

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We have studied on the molecular mechanisms of myogenesis, which consists of series of processes inculding the determination of myogenic cell linages, differentiation induction, expression of muscle-specific protein genes, and formation of contractile structures. The results are summarized as follows : (1) Activin, the most potent mesoderm-inducing factor, dose-dependently induced ectoderm and mesoderm tissues at particular areas of Xenopus embryos. Regulation of the espression of Myf5, a myogenic differentiation factor, was analyzed. (2) Myogenin-knock out mice were produced by gene targetting. In the mice, myoblasts were generated, but mature myocytes were not formed, indicating that myogenin is essential for late stages of muyogenesis. (3) Five clusters of muscle actin genes were discovered, and their expression properties were analyzed. (4) The expression and activation of c-Jun, Cdk2-cyclin A, Cdc2-cyclin B, and Rb play important roles in muscle cell differentiation and dedifferentiation induced by SV40 large T antigen. (5) The system was developed that the mouse skeletal muscle cell line C2 injected into mice defferentiated in vivo. (6) cDNAs were cloned and their primary sequences were determined of profilin, 115kDa alpha-actinin, and cardiac C-protein, which are involved in the regulation of muscle protein assembly during myogenesis. Cofilin, an actin-regulatory protein, was highly expressed during muscle degeneration. The process of actin assembly into cardiac muscle myofibrils was analyzed by electron microscopy using biotin-conjugated actin.