Muscle fiber maturation and aging will be studied from the point of view of defining conditions in vivo and in vitro that contribute to changes in muscle gene expression. Particular attention will be paid to muscle fiber regeneration and the role played by nerve cells and by humoral factors in causing regenerating muscle to express an adult molecular phenotype. Adult-type molecules are distinguished from their embryonic and/or neonatal isoforms by a battery of methods including peptide mapping, 2-dimensional gel electrophoresis and immunological reactivity. At the gene level, switches from embryonic to adult genes will be monitored by use of cDNA probes. Specific molecules to be investigated, all of which show a transition from embryonic to adult isoform synthesis pattern, are myosin heavy chains, myosin light chains, tropomyosin and troponin. Regeneration will be studied in vivo with a cold-injury procedures. Regenerating and normal muscle will also be deinnervated to investigate impact of nerves on gene expression. Satellite cells of normal and regenerating muscle will be isolated and studied in cell culture. A model for muscle fiber regeneration will be established in vitro in order to evaluate effects of aging, electrical activity, growth factors and hormones on muscle fiber synthesis patterns and expression of adult genes. This work is intended to impact on understanding maturation and aging in normal muscle and on understanding muscle diseases in which defects may be associated with adult rather than with embryonic configurations of gene expression.
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