Chaqour Brahim
Department of Cell Biology and Ophthalmology, State University of New York (SUNY) Eye Institute-Downstate Medical Center, Brooklyn, New York 11203, USA.
Trends Dev Biol. 2013;7:59-72.
The circulatory system is the first hierarchically ordered network to form during the development of vertebrates as it is an indispensable means of adequate oxygen and nutrient delivery to developing organs. During the initial phase of vascular development, endothelial lineage-committed cells differentiate, migrate, and coalesce to form the central large axial vessels and their branches. The subsequent phase of vessel expansion (i.e., angiogenesis) involves a cascade of events including endothelial cell migration, proliferation, formation of an immature capillary structure, recruitment of mural cells and deposition of a basement membrane to yield a functional vasculature. These series of events are tightly regulated by the coordinated expression of several angiogenic, morphogenic and guidance factors. The extracellular matrix (ECM) is synthesized and secreted by embryonic cells at the earliest stages of development and forms a pericellular network of bioactive stimulatory and inhibitory angiogenesis regulatory factors. Here we describe the role of a subset of inducible immediate-early gene-encoded, ECM-associated integrin- and heparin-binding proteins referred to as (or Cyr61) and (or ) and their function in the development of the vascular system. Gene-targeting experiments in mice have identified and as critical rate-limiting determinants of endothelial cell differentiation and quiescence, mural cell recruitment and basement membrane formation during embryonic vascular development. Emphasis will be placed on the regulation and function of these molecules and their contextual mode of action during vascular development. Further understanding of the mechanisms of - and -mediated blood vessel expansion and remodeling would enhance the prospects that these molecules provide for the development of new treatments for vascular diseases.
循环系统是脊椎动物发育过程中形成的首个分层有序网络，因为它是向发育中的器官充分输送氧气和营养物质的不可或缺的途径。在血管发育的初始阶段，内皮谱系定向细胞分化、迁移并聚集形成中央大的轴向血管及其分支。随后的血管扩张阶段（即血管生成）涉及一系列事件，包括内皮细胞迁移、增殖、形成不成熟的毛细血管结构、募集壁细胞以及沉积基底膜以产生功能性脉管系统。这些系列事件受到多种血管生成、形态发生和导向因子的协调表达的严格调控。细胞外基质（ECM）在发育的最早阶段由胚胎细胞合成并分泌，形成一个由生物活性刺激和抑制血管生成调节因子组成的细胞周围网络。在这里，我们描述了一组由诱导型即早基因编码、与ECM相关的整合素和肝素结合蛋白（称为Cyr61或CCN1）以及Nov或CCN2）的作用及其在血管系统发育中的功能。小鼠基因靶向实验已确定Cyr61和Nov是胚胎血管发育过程中内皮细胞分化和静止、壁细胞募集和基底膜形成的关键限速决定因素。重点将放在这些分子的调控和功能以及它们在血管发育过程中的背景作用模式上。进一步了解Cyr61和Nov介导的血管扩张和重塑机制将提高这些分子为开发血管疾病新疗法提供的前景。
