EMBRYONIC VASCULAR DEVELOPMENT

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The research in this proposal focuses on the molecular and cellular mechanisms underlying embryonic vascular development. Preliminary experiments show that, during vascular development of Xenopus, vascular precursor cells migrate medially from a position in the lateral mesoderm towards a concentrated source of VEGF below the notochord. Once the angioblasts reach the position of the future dorsal aorta, they cease migration and differentiate. These aspects of vascular development in Xenopus, and more generally, the directed migration of angioblasts in response to VEGF signaling, have not been reported previously. The chemoattractant properties of VEGF may represent a novel mechanism for vascular patterning. The goal of the research in this proposal is to further investigate molecular and cellular basis for the migration of angioblasts within the embryo, and the molecular mechanisms that establish the vascular architecture. The specific aims of the experiments in the proposal are as follows; (1). To accurately describe the formation of the dorsal aorta in Xenopus, 2) To determine the role of the somites during dorsal aorta formation. (3). To determine whether a specific sub-population of angioblasts migrate to form the dorsal aorta. (4). To examine the role of TGF-beta family members in the regulation of dorsal aorta development, and (5). To investigate the origins of vascular precursor cells in the Xenopus embryo. The long term goal of our research is to understand the molecular mechanisms underlying patterning and development of vascular tissues in the embryo. Given the conservation of basic mechanisms underlying vertebrate development, it is extremely likely that the results obtained from these studies of frog embryos will be directly applicable to understanding the pattering of the embryonic vasculature in other organisms, including humans. This research has broad significance because the basic mechanisms underlying embryonic vascular development are likely to be reiterated during vasculogenesis associated with tumorogenesis, wound healing and vascular repair.