Cell-extracellular materix interactions during precardiac cell migration are important in determining the ultimate form and function of the heart. The proposal for a Physicain Scientist Award presents a comprehensive research and educational program that should equip the candidate with the necessary tools to investigate these critical interactions during the early stages of cardiac morphogenesis. Phase I is outlined and includes a curriculum focused on Cell Biology, Immunochemistry, and Developmental Anatomy. A research proposal to be initiated in Phase I and completed in Phase II is presented in detail. Performance during Phase I, defense of the research proposal prior to initiating Phase II, and progress reports on research during Phase II will be reviewed by a faculty Advisory Committee. The research proposal is aimed at delineating the cell- extracellular matrix interactions that effect precardiac cell migration and differentiation in thed mammalian embryo. The studies include: 1) use of whole embryo preparations and monoclonal antibodies against major extracellular matrix components (Collagen types I, III, IV, hyaluronic acid, laminin, fibronectin, basement membrane heparan sulfate proteoglycan) to develop an immunohistochemical map of the apperance and distribution of these components during the period of precardiac cell migration, 2) utilization of monoclonal antibodies specific for molecules known to appear during myoblast differentiation (actin, myosin, desmin intermediate filaments, cell surface epitope) to identify the precardiac cells as a unique subpopulation of the lateral plate mesoderm and to examine the sequence of their expression during the differentiation of the precardiac cells,and 3) investigation of the dynamic cell-extracellular matrix interactions in situ by culturing whole rat embryos in the presence of known inhibitors of normal cell:matrix interactions (Streptomyces hyaluronidase, anti-fibronection antibodies,GRGDS/RGDS, LACA, alpha, alpha dipyridil) during the period of active precardiac cell migration and differentiation.
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| Bogen, S A; Baldwin, H S; Watkins, S C et al. (1992) Association of murine CD31 with transmigrating lymphocytes following antigenic stimulation. Am J Pathol 141:843-54 |
| Baldwin, H S; Jensen, K L; Solursh, M (1991) Myogenic cytodifferentiation of the precardiac mesoderm in the rat. Differentiation 47:163-72 |
| Baldwin, H S; Solursh, M (1989) Degradation of hyaluronic acid does not prevent looping of the mammalian heart in situ. Dev Biol 136:555-9 |
