EMBRYONIC VASCULAR DEVELOPMENT

本文主要研究胚胎血管发育的分子和细胞机制。初步实验表明，在爪蟾的血管发育过程中，血管前体细胞从外侧中胚层向脊索下方的VEGF集中来源向内侧迁移。一旦成血管细胞到达未来背主动脉的位置，它们就停止迁移并分化。非洲爪蟾血管发育的这些方面，以及更一般地说，成血管细胞响应VEGF信号的定向迁移，以前没有报道过。VEGF的化学引诱特性可能代表了一种新的血管形成机制。本课题的研究目的是进一步探讨成血管细胞在胚胎内迁移的分子和细胞基础，以及形成血管结构的分子机制。本课题实验的具体目的如下：（1). 准确描述爪蟾背主动脉的形成；2)确定体在背主动脉形成过程中的作用。（3). 确定一个特定的成血管细胞亚群是否迁移形成背主动脉。（4). 研究tgf - β家族成员在调节背主动脉发育中的作用，以及(5)。目的：探讨非洲爪蟾胚胎血管前体细胞的来源。我们研究的长期目标是了解胚胎中维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是守恒的，从这些青蛙胚胎的研究中获得的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脉管系统的模式。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发生过程中得到重申。

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.