EMBRYONIC VASCULAR DEVELOPMENT

这项建议的研究重点是胚胎血管发育的分子和细胞机制。初步实验表明，在非洲爪蛙血管发育过程中，血管前体细胞从外侧中胚层的某个位置向脊索下集中的血管内皮生长因子来源迁移。一旦血管母细胞到达未来的背主动脉位置，它们就停止迁移和分化。非洲爪哇血管发育的这些方面，以及更广泛地说，血管母细胞响应血管内皮生长因子信号的定向迁移，以前还没有报道。血管内皮生长因子的趋化特性可能代表了一种新的血管构型机制。这项研究的目标是进一步研究血管母细胞在胚胎内迁移的分子和细胞基础，以及建立血管结构的分子机制。方案中实验的具体目标如下：(1)。为了准确地描述非洲爪哇背主动脉的形成，2)确定体节在背主动脉形成中的作用。(3)。以确定特定的血管母细胞亚群是否迁移形成背主动脉。(4)。探讨转化生长因子-β家族成员在背主动脉发育调控中的作用。探讨非洲爪哇胚胎血管前体细胞的起源。我们研究的长期目标是了解胚胎中血管组织形成和发育的分子机制。鉴于脊椎动物发育的基本机制的保守性，这些对青蛙胚胎的研究结果极有可能直接适用于理解包括人类在内的其他生物的胚胎血管系统的模式。这项研究具有广泛的意义，因为胚胎血管发育的基本机制可能在与肿瘤发生、伤口愈合和血管修复相关的血管形成过程中得到重申。

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.