MITOGENIC REGULATION OF SKELETAL MUSCLE DIFFERENTIATION

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The long term goal of this project is to understand how skeletal muscle differentiation is regulated. The specific aims are to determine how certain growth factors repress muscle differentiation, how proliferating myoblasts become "committed" to a post-mitotic state when specific mitogens are withdrawn, and how the M- and B-creatine kinase genes are regulated during terminal muscle differentiation. Major methodologies used in this project are: cell culture, growth factor receptor analysis, mutant selection, somatic genetics, gene cloning, gene sequencing, gene structural analysis, fusion and mutant gene construction, introduction of genes into cells, and analysis of endogenous and exogenous gene expression. Health-related aspects of the project are its contribution toward the understanding of normal development and gene expression. Possible medical applications are to developmental disorders, to genetic diseases, to degenerative muscle diseases, to normal and neoplastic growth regulation and to general clinical diagnostic procedures involving M- and B-creatine kinase.