Role of fibronectin in vascular plexus self-organization during embryogenesis

纤连蛋白在胚胎发生过程中血管丛自组织中的作用

基本信息

批准号：
7341118
负责人：
ANDRAS CZIROK
金额：
$ 25.73万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-02-01 至 2012-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7341118
关键词：
Angioblast Antibodies Area Behavior Biological Assay Blood Vessels Cell Adhesion Cell-Matrix Junction Cells Clinical Complex Computer Simulation Confocal Microscopy Cues Data Development Distal Embryonic Development Endothelial Cells Extracellular Matrix Facility Construction Funding Category Fibronectins Filament Fluorescence Functional disorder Goals Green Fluorescent Proteins Growth Image Integrins Invaded Invasive Label Maintenance Mediating Microscopy Modeling Molecular Nomarski Interference Contrast Microscopy Numbers Optics Pattern Physiological Process Production Property Reagent Research Personnel Resolution Role Spatial Distribution Speed Structure System Therapeutic Tissue Engineering Vascular Endothelial Cell Vascularization Width cell assembly cell motility improved in vivo mathematical model particle progenitor programs receptor response self organization simulation size three dimensional structure tumor growth vasculogenesis

项目摘要

DESCRIPTION (provided by applicant): Vessel formation from mesodermal progenitors, vasculogenesis, is a fundamental process common to both embryonic development and certain pathophysiologies. Recently we showed that the formation of vascular cords from isolated clusters of angioblasts involves extensive invasive activity. During this process, vasculogenic sprouting, a group of endothelial cells invades hundreds of micrometers into avascular areas, and thereby lays down the structure of the primordial vascular plexus. We aim to determine the specific role of fibronectin, and its major endothelial receptors in the process. Specifically, we will (1) determine if fibronectin acts as a guidance cue during vasculogenic sprouting, (2) study the cell-mediated macro- assembly dynamics and turnover of the transient, fibronectin-rich extracellular matrix surrounding the cords of primordial endothelial cells, (3) determine the molecular composition of cell adhesion complexes and the respective roles of integrins avb3 and a5b1, and (4) synthesize the experimental data into a quantitative model of vasculogenesis. Vasculogenic sprouting will be studied in vivo, through automated optical microscopy and a combination of fluorescence-tagged antibodies and GFP constructs, in the presence or absence of perturbing reagents. The long term goal of the project is to understand endothelial cell-ECM interactions in sufficient detail to allow the construction of predictive quantitative models, either for tissue engineering, or to understand developmental morphogenetic processes. Understanding blood vessel development is of overwhelming clinical importance. Our goal, and the goal of other vascular biologists, is to explain the mechanisms that promote or inhibit vessel growth and thus regulate the structure of the vessel network. In particular, endothelial progenitors are in the focus of therapeutic vascularization strategies, tissue engineering, and attempts to block tumor growth.

描述（由申请人提供）：中胚层祖细胞的血管形成，血管生成，是胚胎发育和某些病理生理学共同的基本过程。最近，我们表明，来自血管生成细胞的分离簇的血管绳形成涉及广泛的侵入性活性。在此过程中，血管生成发芽，一组内皮细胞侵入数百微米进入血管区域，从而降低原始血管丛的结构。我们旨在确定纤连蛋白的特定作用及其在此过程中的主要内皮受体。具体而言，我们将（1）确定纤连蛋白在血管生成发芽过程中是否起到指导提示，（2）研究细胞介导的宏观组装动力学和瞬时，富含纤维蛋白的细胞外基质的临时动力学和周围围绕原始内皮细胞和整合细胞内皮组合物组成的组合体的细胞索的细胞外基质（3））的动力学。 A5B1和（4）将实验数据合成为血管生成的定量模型。在存在或不存在扰动试剂的情况下，将通过自动光学显微镜以及荧光标记的抗体和GFP构建体的组合来研究血管发芽。该项目的长期目标是足够详细地了解内皮细胞ECM相互作用，以构建用于组织工程的预测定量模型，或者了解发展性形态发生过程。了解血管发育具有压倒性的临床重要性。我们的目标以及其他血管生物学家的目标是解释促进或抑制血管生长，从而调节血管网络结构的机制。特别是，内皮祖细胞是治疗性血管化策略，组织工程以及试图阻断肿瘤生长的尝试。