PMID- 30139844 OWN - NLM STAT- MEDLINE DCOM- 20181026 LR - 20211204 IS - 1095-9203 (Electronic) IS - 0036-8075 (Linking) VI - 361 IP - 6404 DP - 2018 Aug 24 TI - Endothelial Dab1 signaling orchestrates neuro-glia-vessel communication in the central nervous system. LID - eaao2861 [pii] LID - 10.1126/science.aao2861 [doi] AB - 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-alpha4 and decreased activation of integrin-beta1 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. CI - Copyright (c) 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. FAU - Segarra, Marta AU - Segarra M AUID- ORCID: 0000-0002-0956-8490 AD - Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, University of Frankfurt, D-60438 Frankfurt am Main, Germany. FAU - Aburto, Maria R AU - Aburto MR AUID- ORCID: 0000-0001-5806-251X AD - Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, University of Frankfurt, D-60438 Frankfurt am Main, Germany. AD - Focus Program Translational Neurosciences, University of Mainz, D-55131 Mainz, Germany. FAU - Cop, Florian AU - Cop F AUID- ORCID: 0000-0003-1466-699X AD - Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, University of Frankfurt, D-60438 Frankfurt am Main, Germany. FAU - Llao-Cid, Cecilia AU - Llao-Cid C AD - Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, University of Frankfurt, D-60438 Frankfurt am Main, Germany. FAU - Hartl, Ricarda AU - Hartl R AD - Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, University of Frankfurt, D-60438 Frankfurt am Main, Germany. FAU - Damm, Miriam AU - Damm M AD - Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, University of Frankfurt, D-60438 Frankfurt am Main, Germany. AD - Focus Program Translational Neurosciences, University of Mainz, D-55131 Mainz, Germany. FAU - Bethani, Ioanna AU - Bethani I AD - Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, University of Frankfurt, D-60438 Frankfurt am Main, Germany. FAU - Parrilla, Marta AU - Parrilla M AD - Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, University of Frankfurt, D-60438 Frankfurt am Main, Germany. AD - Max Planck Institute for Brain Research, D-60438 Frankfurt am Main, Germany. FAU - Husainie, Dewi AU - Husainie D AUID- ORCID: 0000-0001-5200-0545 AD - Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, University of Frankfurt, D-60438 Frankfurt am Main, Germany. AD - Max Planck Institute for Brain Research, D-60438 Frankfurt am Main, Germany. FAU - Schanzer, Anne AU - Schanzer A AD - Institute of Neuropathology, University of Giessen, D-35392 Giessen, Germany. FAU - Schlierbach, Hannah AU - Schlierbach H AD - Institute of Neuropathology, University of Giessen, D-35392 Giessen, Germany. FAU - Acker, Till AU - Acker T AD - Institute of Neuropathology, University of Giessen, D-35392 Giessen, Germany. FAU - Mohr, Laura AU - Mohr L AD - Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, University of Frankfurt, D-60438 Frankfurt am Main, Germany. FAU - Torres-Masjoan, Laia AU - Torres-Masjoan L AD - Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, University of Frankfurt, D-60438 Frankfurt am Main, Germany. FAU - Ritter, Mathias AU - Ritter M AD - Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, University of Frankfurt, D-60438 Frankfurt am Main, Germany. FAU - Acker-Palmer, Amparo AU - Acker-Palmer A AUID- ORCID: 0000-0002-8107-927X AD - Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, University of Frankfurt, D-60438 Frankfurt am Main, Germany. acker-palmer@bio.uni-frankfurt.de. AD - Focus Program Translational Neurosciences, University of Mainz, D-55131 Mainz, Germany. AD - Max Planck Institute for Brain Research, D-60438 Frankfurt am Main, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (Cell Adhesion Molecules, Neuronal) RN - 0 (Dab1 protein, mouse) RN - 0 (Extracellular Matrix Proteins) RN - 0 (Integrin beta1) RN - 0 (LDL-Receptor Related Proteins) RN - 0 (Lama4 protein, mouse) RN - 0 (Laminin) RN - 0 (Nerve Tissue Proteins) RN - 0 (Reelin Protein) RN - 0 (low density lipoprotein receptor-related protein 8) RN - EC 3.4.21.- (Reln protein, mouse) RN - EC 3.4.21.- (Serine Endopeptidases) SB - IM CIN - Science. 2018 Aug 24;361(6404):754-755. PMID: 30139860 MH - Animals MH - Blood-Brain Barrier/cytology/physiology MH - Cell Adhesion Molecules, Neuronal/genetics/metabolism MH - *Cell Communication MH - Cell Movement MH - Cerebral Cortex/*blood supply MH - Endothelium, Vascular/metabolism/*physiology MH - Extracellular Matrix Proteins/genetics/metabolism MH - Female MH - Gene Deletion MH - Integrin beta1/metabolism MH - LDL-Receptor Related Proteins/genetics/metabolism MH - Laminin/metabolism MH - Male MH - Mice MH - Mice, Knockout MH - *Neovascularization, Physiologic MH - Nerve Tissue Proteins/genetics/*metabolism MH - Neuroglia/cytology/metabolism/*physiology MH - Neurons/metabolism/*physiology MH - Reelin Protein MH - Retinal Vessels/cytology/*physiology MH - Serine Endopeptidases/genetics/metabolism MH - Signal Transduction EDAT- 2018/08/25 06:00 MHDA- 2018/10/27 06:00 CRDT- 2018/08/25 06:00 PHST- 2017/07/04 00:00 [received] PHST- 2018/07/05 00:00 [accepted] PHST- 2018/08/25 06:00 [entrez] PHST- 2018/08/25 06:00 [pubmed] PHST- 2018/10/27 06:00 [medline] AID - 361/6404/eaao2861 [pii] AID - 10.1126/science.aao2861 [doi] PST - ppublish SO - Science. 2018 Aug 24;361(6404):eaao2861. doi: 10.1126/science.aao2861.