1. Endothelial Dab1 signaling orchestrates neuro-glia-vessel communication in the central nervous system.
- Author
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Segarra M, Aburto MR, Cop F, Llaó-Cid C, Härtl R, Damm M, Bethani I, Parrilla M, Husainie D, Schänzer A, Schlierbach H, Acker T, Mohr L, Torres-Masjoan L, Ritter M, and Acker-Palmer A
- Subjects
- Animals, Blood-Brain Barrier cytology, Blood-Brain Barrier physiology, Cell Adhesion Molecules, Neuronal genetics, Cell Adhesion Molecules, Neuronal metabolism, Cell Movement, Endothelium, Vascular metabolism, Extracellular Matrix Proteins genetics, Extracellular Matrix Proteins metabolism, Female, Gene Deletion, Integrin beta1 metabolism, LDL-Receptor Related Proteins genetics, LDL-Receptor Related Proteins metabolism, Laminin metabolism, Male, Mice, Mice, Knockout, Nerve Tissue Proteins genetics, Neuroglia cytology, Neuroglia metabolism, Neurons metabolism, Reelin Protein, Retinal Vessels cytology, Serine Endopeptidases genetics, Serine Endopeptidases metabolism, Signal Transduction, Cell Communication, Cerebral Cortex blood supply, Endothelium, Vascular physiology, Neovascularization, Physiologic, Nerve Tissue Proteins metabolism, Neuroglia physiology, Neurons physiology, Retinal Vessels physiology
- Abstract
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., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2018
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