Endothelial Dab1 signaling orchestrates neuro-glia-vessel communication in the central nervous system
Endothelial Dab1 signaling orchestrates neuro-glia-vessel communication in the central nervous system
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DOI：
10.1126/science.aao2861
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发表时间：
2018-08-24
期刊：
影响因子：
56.9
通讯作者：
Acker-Palmer, Amparo
中科院分区：
文献类型：
--
作者：
Segarra, Marta;Aburto, Maria R.;Acker-Palmer, Amparo
神经血管单位（NVU）的结构是由神经元、胶质细胞和血管细胞的通讯控制的。我们发现，神经元导向因子reelin具有促血管生成活性，确保内皮细胞（EC）与胶质细胞的通信，以控制神经元迁移和血脑屏障在小鼠脑中的建立。载脂蛋白E受体2（ApoER 2）和失能1（Dab 1）在内皮细胞中的表达是视网膜和大脑皮层血管化所必需的。EC中Dab 1的缺失导致神经胶质细胞中层粘连蛋白-α 4的分泌减少和整合素-β 1的活化减少，这反过来控制神经元迁移和NVU的屏障特性。因此，血管内皮中的reelin信号传导是神经胶质血管通信所必需的指导性和整合性线索。
The architecture of the neurovascular unit (NVU) is controlled by the communication of neurons, glia, and vascular cells. We found that the neuronal guidance cue reelin possesses proangiogenic activities that ensure the communication of endothelial cells (ECs) with the glia to control neuronal migration and the establishment of the blood-brain barrier in the mouse brain. Apolipoprotein E receptor 2 (ApoER2) and Disabled1 (Dab1) expressed in ECs are required for vascularization of the retina and the cerebral cortex. Deletion of Dab1 in ECs leads to a reduced secretion of laminin-alpha 4 and decreased activation of integrin-beta 1 in glial cells, which in turn control neuronal migration and barrier properties of the NVU. Thus, reelin signaling in the endothelium is an instructive and integrative cue essential for neuro-glia-vascular communication.