EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution
EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution
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DOI：
10.1242/dev.002576
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发表时间：
2007-08-15
期刊：
影响因子：
4.6
通讯作者：
Ye, Weilan
中科院分区：
文献类型：
--
作者：
Schmidt, Maike;Paes, Kim;Ye, Weilan
在萌芽血管生成过程中，内皮细胞（EC）组以称为萌芽的单位迁移在一起。在这项研究中，我们证明，血管特异性分泌因子EGFL7调节每个芽内EC的适当空间组织，并影响它们的集体运动。在纯合Egfl7敲除小鼠中，尽管EC正常增殖，但许多器官中的血管发育延迟，并且50%的敲除胚胎在子宫内死亡。突变血管中的EC形成异常聚集体，并且血管基底膜标记物胶原IV被错误定位，这表明EC未能识别其邻居的正确空间位置。虽然单个内皮细胞的迁移能力在隔离不受EGFL7的损失，异常的空间组织中的突变组织减少了他们的集体运动的内皮细胞。使用体外和体内分析，我们表明，EGFL7是一个组成部分的间质细胞外基质沉积在基部两侧的芽，一个位置适合于传递位置信息到相邻的EC。总之，我们建议EGFL7通过确保每个EC在新生芽中的正确定位来定义EC运动的最佳路径。
During sprouting angiogenesis, groups of endothelial cells (ECs) migrate together in units called sprouts. In this study, we demonstrate that the vascular-specific secreted factor EGFL7 regulates the proper spatial organization of ECs within each sprout and influences their collective movement. In the homozygous Egfl7-knockout mice, vascular development is delayed in many organs despite normal EC proliferation, and 50% of the knockout embryos die in utero. ECs in the mutant vasculatures form abnormal aggregates and the vascular basement membrane marker collagen IV is mislocalized, suggesting that ECs fail to recognize the proper spatial position of their neighbors. Although the migratory ability of individual ECs in isolation is not affected by the loss of EGFL7, the aberrant spatial organization of ECs in the mutant tissues decreases their collective movement. Using in vitro and in vivo analyses, we showed that EGFL7 is a component of the interstitial extracellular matrix deposited on the basal sides of sprouts, a location suitable for conveying positional information to neighboring ECs. Taken together, we propose that EGFL7 defines the optimal path of EC movement by assuring the correct positioning of each EC in a nascent sprout.