BVES AND INTRACARDIAC ARTERY DEVELOPMENT

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Heart development involves the generation and interaction of diverse cell types to form a functional organ. Myocytes, endocardium, fibroblasts, epicardium, vascular endothelium and smooth muscle cells are the primary cell types that comprise the heart. The proepicardial organ is the source of many of these cells. It is a transitory embryonic structure whose progeny form, amongst other structures, the epicardium and intracardiac arteries including the coronary arteries. Thus, an understanding of the role of the proepicardial organ and its progeny is essential for an understanding of heart development. In an effort to identify the molecular mechanisms governing heart organogenesis, we have isolated novel cardiac-specific messages expressed during morphogenesis. One such message, Bves, is expressed in most, if not all cells of the eproepicardial organ, migrating epicardial, delaminated freely migratory mesenchyme and cardiac vascular smooth muscle cells. In addition, the subcellular localization of Bves undergoes a dramatic change with differentiation of this cell lineage. Our aims will determine the normal pattern of Bves expression during this complex process (aim 1), how Bves function is altered by known mutations in cardiac morphogenesis (aim 2) and how loss of Bves function potentially alters morphogenesis (aim 3). Taken together these aims will determine the function(s) of Bves, its role in the generation of cardiac blood vessels and basic insight into intracardiac artery development.