DEVELOPMENTAL SIGNALING OF SMOOTH MUSCLE DIFFERENTIATION

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Our current knowledge regarding the differentiation of smooth muscle cells during early embryonic development is severely lacking. Few studies involving the recent advances in molecular genetics have been directed at this critical developmental question. The long term objectives of this proposal are to determine the developmental signals necessary for the differentiation and maturation of smooth muscle cells. These processes require precise timing during early embryonic development and are intimatel associated with the normal development and function of a variety of tissues and organs. Studies have shown that the accumulation of actin within the differentiating smooth muscle cell is one of the primary factors associated with the development of the mature smooth muscle cell morphology. Our preliminary studies have demonstrated that gamma-enteric actin is the key cytoskeletal element found within the smooth muscle cells of the developing gastrointestinal tract. In this present application, we propose to examine smooth muscle cell differentiation in the developing rat gut by a molecular analysis of the gamma-enteric smooth muscle actin gene and its expression. We will clarify the tissue-specific expression of the gamma-enteric actin mRNA in the developing rat gastrointestinal tract and isolate, sequence and characterize the gamma-enteric actin gene. In addition, we will identify the putative cis-acting regulatory domains and trans-acting regulatory proteins associated with the normal expression of the gamma-enteric smooth muscle actin gene during the differentiation of smooth muscle cells. We will utilize these studies as a basis to investigate the neurotrophic influences of sympathetic ganglia on the differentiation and maturation of smooth muscle cells in the developing rat gastrointestinal tract. These studies will provide clues as to the developmental signals associated with the differentiation of smooth muscle cells in the developing rat gastrointestinal tract. These studies will provide clues as to the developmental signals associated with the differentiation of smooth muscle cells in the developing rat gut. The identification of these processes in the developing rat gut will provide the framework for our understanding of the differentiation and development of smooth muscle cells in general. At present, our current understanding of the genetic or epigenetic regulation of any developmentally important gene is lacking. The studies proposed in this application will provide us with the unique opportunity to begin to unravel these complex issues in association with the differentiation of smooth muscle cells.