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EMBRYONIC VASCULAR DEVELOPMENT

胚胎血管发育

基本信息

批准号：
6527510
负责人：
PAUL ANTHONY KRIEG
金额：
$ 23.43万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-08-01 至 2004-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6527510
关键词：
Xenopus angiogenesis aorta blood vessels cell differentiation cell migration cell proliferation chemoattractants embryo /fetus embryogenesis in situ hybridization transforming growth factors vascular endothelial growth factors vertebrate embryology

项目摘要

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.

本项目的研究重点是胚胎血管发育的分子和细胞机制。初步的实验表明，在血管发育的爪蟾，血管前体细胞迁移内侧从一个位置在侧中胚层向集中的来源VEGF脊索下方。一旦成血管细胞到达未来背主动脉的位置，它们停止迁移和分化。非洲爪蟾血管发育的这些方面，以及更普遍的，成血管细胞响应VEGF信号传导的定向迁移，以前没有报道过。VEGF的化学引诱特性可能代表了血管图案化的新机制。本研究的目的是进一步研究胚胎内成血管细胞迁移的分子和细胞基础，以及建立血管结构的分子机制。建议中实验的具体目的如下：（1）。为了准确描述爪蟾背主动脉的形成，2）确定体节在背主动脉形成中的作用。（三）、确定成血管细胞的特定亚群是否迁移形成背主动脉。（四）、研究TGF-β家族成员在背主动脉发育调控中的作用;（5）.探讨爪蟾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维管组织形成和发育的分子机制。考虑到脊椎动物发育的基本机制是保守的，从青蛙胚胎的这些研究中获得的结果极有可能直接适用于理解其他生物（包括人类）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很可能在与肿瘤发生，伤口愈合和血管修复相关的血管发生过程中得到重申。