This proposal addresses several key questions regarding the molecular mechanisms underlying the regulation of select skeletal muscle genes. Identification of networks that regulate muscle-specific genes would have fundamental implications for the generation of strategies to replace muscle types damaged by degenerative diseases or injury, and have broad relevance to mechanisms of tissue transdifferentiation. In the teleost vertebrate S. macrurus, skeletal muscle fibers fully differentiate only to undergo fusion and subsequent conversion into electrocytes, i.e, the noncontractile currentproducing cells of the electric organ. The mature electric organ shares many but not all cellular features with myogenic cells maintaining the expression of only a subset of the contractile protein profile. Our long term goal is to characterize the genetic, cellular and molecular factors that define the myogenic program in S. macrurus. The main objective of the proposed research is to determine how muscle genes in electrocytes are regulated by the MyoD family of myogenic regulatory factors (MRFs). The proposed studies test the hypothesis that the regulation of muscle genes by MRFs differs between muscle and electric organ.
Our specific aims are: (1) to define the expression of MRF transcripts and protein products in mature muscle and electric organ at the cellular level, (2) characterize the expression pattern of MRFs during the transdifferentiation of muscle to electric organ, and (3) identify genes regulated by MRFs in muscle versus electric organ. To accomplish these aims, a collection of tools that is amenable to experimentation with S. macrurus has been assembled. Importantly, we can easily induce the transdifferentiation of muscle to electric organ, and we know the changes that occur in muscle protein expression. These studies use a novel but simple model system to further our current understanding of the molecular mechanisms involving MRFs in the maintenance of the differentiated muscle phenotype.
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