Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, University of Frankfurt, D-60438 Frankfurt am Main, Germany.
Focus Program Translational Neurosciences, University of Mainz, D-55131 Mainz, Germany.
Science. 2018 Aug 24;361(6404). doi: 10.1126/science.aao2861.
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-α4 and decreased activation of integrin-β1 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.
神经血管单元 (NVU) 的结构由神经元、神经胶质和血管细胞的通讯控制。我们发现，神经元导向因子 reelin 具有促血管生成活性，可确保内皮细胞 (ECs) 与神经胶质的通讯，以控制神经元迁移和小鼠大脑中血脑屏障的建立。ECs 中表达的载脂蛋白 E 受体 2 (ApoER2) 和Disabled1 (Dab1) 对于视网膜和大脑皮层的血管生成是必需的。ECs 中 Dab1 的缺失导致层粘连蛋白-α4 的分泌减少和神经胶质细胞中整合素-β1 的激活减少，进而控制神经元迁移和 NVU 的屏障特性。因此，内皮细胞中的 reelin 信号是神经胶质血管通讯所必需的指导和整合信号。
