The subject of this research concerns elucidating the molecular basis for Cell Surface:ECM interactions during early cardiac morphogenesis. Specifically, we propose to study an embryonic chicken and mouse cell surface protein described herein, and its physical interaction with collagen. We predict that these partially characterized collagen binding proteins (CBP) are part of an intergral membrane protein complex that mediates cell surface:collagen interactions during heart development. In order to test this prediction the studies proposed below will: 1) Examine in more detail the physical characteristics of CBP. 2) Investigate the subunit structure of CBP by use of monoclonal antibodies. 3) Investigate by direct experimentation the role collagen and CBP play in differentiation and morphogenesis of precardiac mesoderm. 4) Examine the behavior of ventricular endothelium versus cushion endothelium when the cells are cultured in the presence of various antibodies and synthetic peptides. 5) Examine the relationship between cell:ECM interactions and the acquisition of specific physiological properties (contractility, ionic coupling, membrane excitability). 6) Use gene cloning technology in order to prepare cDNA to CBP. 7) Employ the cDNAs in studies of CBP gene expression and CBP primary sequence, and as a means of producing biochemical amounts of pure CBP. In addition to contributing to our understanding of early vertebrate morphogenesis it is conceivable that these studies could help illuminate some of the fundamental mechanisms responsible for cardiac malformations. A very large proportion of cardiac birth defects are attributable to structures that receive contributions from endocardial cushions. In this proposal we describe studies concerning the morphogenesis of these important primordia.
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