During development contractile proteins undergo a precise association known as myofibrillogenesis. Further interactions are necessary to form the rod-shaped phenotype essential to contractility. These interactions between cytoskeletal components, membrane receptors (integrins) and ECM are fundamental for formation of rod-shaped growth of myocytes. Formation of ECM-integrin complex is proposed to be critical element in transmission of mechanical signals to myocyte. PI has shown that composition and orientation of ECM, presence of integrins, and alignment of cytoskeletal proteins are essential to the formation of rod-shaped phenotype. These studies further show that myocytes on collagen matrix assume rod-shaped phenotype and spatially express components of ECM-integrin complex. Hypothesis: an intact ECM-integrin-cytoskeletal linkage is critical to myocyte phenotype and function. Also, the arrangement and type of ECM components acting via integrins can regulate myocyte shape and the assembly of myofibrils into a phenotype that can respond to chemical and mechanical signaling similar to that observed in vivo. Proposed studies are:
Aim 1 - Determine role of ECM, integrins, and cytoskeleton on myofibrillogenesis and phenotype in vitro.
Aim 2 - Determine role of mechanical tension in formation and maintenance of phenotype.
Aim 3 - Determine how these factors regulate myofibrillogenesis and phenotype in situ heart using whole embryo culture.
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