| Co-Investigator(Kenkyū-buntansha) |
MASAKI Tomoh Kyoto University, School of Medicine, Department of Pharmacology, Professor, 医学部, 教授 (60009991)
NABESHIMA Yoichi National Institute of Neuroscience Division of Molecular Genetics, Chief Inverst, 部長 (60108024)
SATO Noriyuki Kyoto University, Department of Zoology Associate Professor, 理学部, 助教授 (30025481)
ASASHIMA Makoto University of Tokyo, Coll.Gen.Educ. Department of Biology, Professor, 教養学部, 教授 (00090564)
SHIMADA Yutaka Chiba University, School of Medicine, Department of Anatomy, Professor, 医学部, 教授 (70009116)
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| Research Abstract |
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.
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