The endothelial-cell-derived secreted factor Egfl7 regulates vascular tube formation
The endothelial-cell-derived secreted factor Egfl7 regulates vascular tube formation
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DOI：
10.1038/nature02416
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发表时间：
2004-04-15
期刊：
影响因子：
64.8
通讯作者：
Ye, WL
中科院分区：
文献类型：
--
作者：
Parker, LH;Schmidt, M;Ye, WL
血管发育是一个复杂但有序的过程，受到严格的调控。由周围细胞产生的许多分泌因子调节内皮细胞（EC）分化、增殖、迁移和聚结成索状结构（1，2）。然后，血管索经历小管形成以形成具有中央管腔的血管（3，4）。但是，很少有人知道如何在体内调控微管发生。在这里，我们报告了一个新的EC衍生的分泌因子，EGF样结构域7（Egfl7）的鉴定和表征。Egfl7在与组织增殖相关的脉管系统中以高水平表达，并且在正常成人组织中的大多数成熟血管中下调。斑马鱼胚胎中Egfl7功能的丧失特异性地阻断了血管小管发生。我们揭示了一个动态的过程，在此过程中，逐渐分离和适当的空间排列的成血管细胞允许随后的组装血管管。这个过程在Egfl7敲低胚胎中未能发生，导致维管形成失败。我们的研究定义了一种调节剂，它控制着血管发生中一个特定而重要的步骤。
Vascular development is a complex but orderly process that is tightly regulated. A number of secreted factors produced by surrounding cells regulate endothelial cell (EC) differentiation, proliferation, migration and coalescence into cord-like structures(1,2). Vascular cords then undergo tubulogenesis to form vessels with a central lumen(3,4). But little is known about how tubulogenesis is regulated in vivo. Here we report the identification and characterization of a new EC-derived secreted factor, EGF-like domain 7 (Egfl7). Egfl7 is expressed at high levels in the vasculature associated with tissue proliferation, and is downregulated in most of the mature vessels in normal adult tissues. Loss of Egfl7 function in zebrafish embryos specifically blocks vascular tubulogenesis. We uncover a dynamic process during which gradual separation and proper spatial arrangement of the angioblasts allow subsequent assembly of vascular tubes. This process fails to take place in Egfl7 knockdown embryos, leading to the failure of vascular tube formation. Our study defines a regulator that controls a specific and important step in vasculogenesis.