Budding angiogenesis and neovascularization have been studied in detail for several years and as a result, we know quite a bit about the biology and biochemistry of angiogenesis. In contrast, nothing is known concerning the process of formation of the initial vascular system in the early embryo. This is because until now, probes have not been available for identifying the earliest embryonic endothelial cells and for following their organization into the vascular tree which subsequently serves as the source of cells for the later process of budding angiogenesis and tissue vascularization. We have developed monoclonal antibodies which react with these early endothelial cells as they first arise from the mesoderm of quail blastodiscs. Using these antibodies in conjunction with monoclonal antibodies specific for individual extracellular matrix molecules (ECM) we propose to first describe the formation of the initial vascular tree and changes which occur in the ECM during this process. Second, we will examine the interaction between the developing vascular endothelium and individual ECM molecules both in cultured embryos and in cultures of isolated endothelial cells. Third, we will identify the receptors in the developing endothelium responsible for adhesion to the ECM. Fourth, we will study the ability of developing endothelial cells to respond to known chemotatic or angiogenic substances as well as attempt to discover whether or not such factors play a role in the establishment of the initial embryonic vasculature. Upon completion of the work proposed here, we will have defined the process of early vascular development, determined the role the ECM plays in this process and gained some insight into the origin and organization of the earliest presumptive vascular endothelial cells into the first vessels of the developing embryo.
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