Parker Leon H, Schmidt Maike, Jin Suk-Won, Gray Alane M, Beis Dimitris, Pham Thinh, Frantz Gretchen, Palmieri Susan, Hillan Kenneth, Stainier Didier Y R, De Sauvage Frederic J, Ye Weilan
Molecular Biology Department, Genentech Inc., South San Francisco, California 94080, USA.
Nature. 2004 Apr 15;428(6984):754-8. doi: 10.1038/nature02416.
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. Vascular cords then undergo tubulogenesis to form vessels with a central lumen. 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.
血管发育是一个复杂但有序的过程，受到严格调控。周围细胞产生的多种分泌因子调节内皮细胞（EC）的分化、增殖、迁移以及聚集成索状结构。血管索随后经历血管生成以形成具有中央管腔的血管。但关于血管生成在体内如何被调控，人们知之甚少。在此，我们报告一种新的内皮细胞衍生分泌因子——表皮生长因子样结构域7（Egfl7）的鉴定和特性。Egfl7在与组织增殖相关的脉管系统中高水平表达，而在正常成年组织的大多数成熟血管中表达下调。斑马鱼胚胎中Egfl7功能的缺失特异性地阻断了血管生成。我们揭示了一个动态过程，在此过程中，成血管细胞的逐渐分离和适当的空间排列使得随后血管管的组装成为可能。这一过程在Egfl7基因敲低的胚胎中无法发生，导致血管管形成失败。我们的研究确定了一个调控因子，它控制血管生成中一个特定且重要的步骤。
