The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system (Publication with Expression of Concern)
The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system (Publication with Expression of Concern)
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DOI：
10.1038/nature03080
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发表时间：
2004-11-11
期刊：
影响因子：
64.8
通讯作者：
Eichmann, A
中科院分区：
文献类型：
--
作者：
Lu, XW;le Noble, F;Eichmann, A
血管和神经是具有高度解剖相似性的复杂分支结构。血管和神经的引导必须精细地调节，以确保两个系统的正确布线。已经鉴定了几种轴突导向调节剂，其中一些也在内皮细胞中表达;然而，它们的导向功能在血管系统中保守的程度仍然不完全清楚。我们在这里表明，排斥netrin受体UNC 5 B表达的血管系统的内皮尖端细胞。在小鼠中Unc 5 b基因的破坏，或在斑马鱼中Unc 5 b或netrin-1a的破坏，导致内皮尖端细胞丝状伪足的异常延伸，过度的血管分支和异常导航。Netrin-1导致内皮丝足收缩，但仅当UNC 5 B存在时。因此，UNC 5 B在控制血管系统形态发生的内皮细胞中起排斥性netrin受体的作用。
Blood vessels and nerves are complex, branched structures that share a high degree of anatomical similarity. Guidance of vessels and nerves has to be exquisitely regulated to ensure proper wiring of both systems. Several regulators of axon guidance have been identified and some of these are also expressed in endothelial cells; however, the extent to which their guidance functions are conserved in the vascular system is still incompletely understood. We show here that the repulsive netrin receptor UNC5B is expressed by endothelial tip cells of the vascular system. Disruption of the Unc5b gene in mice, or of Unc5b or netrin-1a in zebrafish, leads to aberrant extension of endothelial tip cell filopodia, excessive vessel branching and abnormal navigation. Netrin-1 causes endothelial filopodial retraction, but only when UNC5B is present. Thus, UNC5B functions as a repulsive netrin receptor in endothelial cells controlling morphogenesis of the vascular system.