The netrin receptor UNC5B promotes angiogenesis in specific vascular beds
The netrin receptor UNC5B promotes angiogenesis in specific vascular beds
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DOI：
10.1242/dev.013623
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发表时间：
2008-02-15
期刊：
影响因子：
4.6
通讯作者：
Li, Dean Y.
中科院分区：
文献类型：
--
作者：
Navankasattusas, Sutip;Whitehead, Kevin J.;Li, Dean Y.
有新的证据表明，经典的神经导向因子netrin也可以指导血管的生长。我们删除了编码UNC 5 B的基因，UNC 5 B是netrin家族指导分子的受体，特别是在小鼠胚胎内皮细胞内。其结果是胎盘迷路小动脉严重的结构和功能缺陷，首先导致脐动脉血流逆转，最终导致胚胎死亡。由于这是突变胚胎中血管异常的唯一可检测位点，并且由于野生型滋养外胚层不能挽救表型，因此我们提出UNC 5 B介导的信号传导是胎儿胎盘血管生成的特异性和自主性组分。UNC 5 B的破坏代表了仅在胎儿-胎盘血管系统内起作用的突变的独特实例，并且忠实地概括了临床子宫胎盘功能不全的结构和生理特征。这种对UNC 5 B的促血管生成但空间受限的需求并不是鼠发育所独有的，因为斑马鱼中UNC 5 b直系同源物的敲低类似地导致副索血管（淋巴系统的前体）的特异性和高度渗透性缺失。
There is emerging evidence that the canonical neural guidance factor netrin can also direct the growth of blood vessels. We deleted the gene encoding UNC5B, a receptor for the netrin family of guidance molecules, specifically within the embryonic endothelium of mice. The result is a profound structural and functional deficiency in the arterioles of the placental labyrinth, which leads first to flow reversal in the umbilical artery and ultimately to embryonic death. As this is the only detectable site of vascular abnormality in the mutant embryos, and because the phenotype cannot be rescued by a wild-type trophectoderm, we propose that UNC5B-mediated signaling is a specific and autonomous component of fetal-placental angiogenesis. Disruption of UNC5B represents a unique example of a mutation that acts solely within the fetal-placental vasculature and one that faithfully recapitulates the structural and physiological characteristics of clinical uteroplacental insufficiency. This pro-angiogenic, but spatially restricted requirement for UNC5B is not unique to murine development, as the knock-down of the Unc5b ortholog in zebrafish similarly results in the specific and highly penetrant absence of the parachordal vessel, the precursor to the lymphatic system.