Endothelial Dab1 signaling orchestrates neuro-glia-vessel communication in the central nervous system
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 migra...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2018-08, Vol.361 (6404) |
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| creator | Segarra, Marta Aburto, Maria R Cop, Florian Llaó-Cid, Cecília Härtl, Ricarda Damm, Miriam Bethani, Ioanna Parrilla, Marta Husainie, Dewi Schänzer, Anne Schlierbach, Hannah Acker, Till Mohr, Laura Torres-Masjoan, Laia Ritter, Mathias Acker-Palmer, Amparo |
| description | 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. |
| doi_str_mv | 10.1126/science.aao2861 |
| format | Article |
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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.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.aao2861</identifier><identifier>PMID: 30139844</identifier><language>eng</language><publisher>United States: The American Association for the Advancement of Science</publisher><subject>Activation ; Anatomy ; Animals ; Apolipoprotein E ; Apolipoproteins ; Architecture ; Astrocytes ; Axon guidance ; Blood vessels ; Blood-brain barrier ; Brain ; Brain architecture ; Cell migration ; Cell proliferation ; Central nervous system ; Cerebral cortex ; Clonal deletion ; Communication ; Communications systems ; Defects ; Disabled-1 protein ; Docking ; Embryos ; Endothelial cells ; Endothelium ; Extracellular matrix ; Filopodia ; Glycoproteins ; Growth factors ; Homeostasis ; Individualized Instruction ; Integrity ; Laminin ; Membrane permeability ; Mice ; Migration ; Nervous system ; Networks ; Neural networks ; Neuronal-glial interactions ; Neurons ; Nutrients ; Permeability ; Receptors ; Retina ; Secretion ; Stimuli ; Vascular endothelial growth factor ; Vascular system</subject><ispartof>Science (American Association for the Advancement of Science), 2018-08, Vol.361 (6404)</ispartof><rights>Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.</rights><rights>Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c437t-1c62e9b676f604294a89cde86fa332ba832be0935d4d70f21aacbfbd77cc7e1e3</citedby><cites>FETCH-LOGICAL-c437t-1c62e9b676f604294a89cde86fa332ba832be0935d4d70f21aacbfbd77cc7e1e3</cites><orcidid>0000-0001-5806-251X ; 0000-0001-5200-0545 ; 0000-0002-8107-927X ; 0000-0003-1466-699X ; 0000-0002-0956-8490</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,2871,2872,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30139844$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Segarra, Marta</creatorcontrib><creatorcontrib>Aburto, Maria R</creatorcontrib><creatorcontrib>Cop, Florian</creatorcontrib><creatorcontrib>Llaó-Cid, Cecília</creatorcontrib><creatorcontrib>Härtl, Ricarda</creatorcontrib><creatorcontrib>Damm, Miriam</creatorcontrib><creatorcontrib>Bethani, Ioanna</creatorcontrib><creatorcontrib>Parrilla, Marta</creatorcontrib><creatorcontrib>Husainie, Dewi</creatorcontrib><creatorcontrib>Schänzer, Anne</creatorcontrib><creatorcontrib>Schlierbach, Hannah</creatorcontrib><creatorcontrib>Acker, Till</creatorcontrib><creatorcontrib>Mohr, Laura</creatorcontrib><creatorcontrib>Torres-Masjoan, Laia</creatorcontrib><creatorcontrib>Ritter, Mathias</creatorcontrib><creatorcontrib>Acker-Palmer, Amparo</creatorcontrib><title>Endothelial Dab1 signaling orchestrates neuro-glia-vessel communication in the central nervous system</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>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.</description><subject>Activation</subject><subject>Anatomy</subject><subject>Animals</subject><subject>Apolipoprotein E</subject><subject>Apolipoproteins</subject><subject>Architecture</subject><subject>Astrocytes</subject><subject>Axon guidance</subject><subject>Blood vessels</subject><subject>Blood-brain barrier</subject><subject>Brain</subject><subject>Brain architecture</subject><subject>Cell migration</subject><subject>Cell proliferation</subject><subject>Central nervous system</subject><subject>Cerebral cortex</subject><subject>Clonal deletion</subject><subject>Communication</subject><subject>Communications systems</subject><subject>Defects</subject><subject>Disabled-1 protein</subject><subject>Docking</subject><subject>Embryos</subject><subject>Endothelial cells</subject><subject>Endothelium</subject><subject>Extracellular 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Dab1 signaling orchestrates neuro-glia-vessel communication in the central nervous system</title><author>Segarra, Marta ; Aburto, Maria R ; Cop, Florian ; Llaó-Cid, Cecília ; Härtl, Ricarda ; Damm, Miriam ; Bethani, Ioanna ; Parrilla, Marta ; Husainie, Dewi ; Schänzer, Anne ; Schlierbach, Hannah ; Acker, Till ; Mohr, Laura ; Torres-Masjoan, Laia ; Ritter, Mathias ; Acker-Palmer, Amparo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c437t-1c62e9b676f604294a89cde86fa332ba832be0935d4d70f21aacbfbd77cc7e1e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Activation</topic><topic>Anatomy</topic><topic>Animals</topic><topic>Apolipoprotein E</topic><topic>Apolipoproteins</topic><topic>Architecture</topic><topic>Astrocytes</topic><topic>Axon guidance</topic><topic>Blood vessels</topic><topic>Blood-brain barrier</topic><topic>Brain</topic><topic>Brain 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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. 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| source | Jstor Complete Legacy; Science Magazine |
| subjects | Activation Anatomy Animals Apolipoprotein E Apolipoproteins Architecture Astrocytes Axon guidance Blood vessels Blood-brain barrier Brain Brain architecture Cell migration Cell proliferation Central nervous system Cerebral cortex Clonal deletion Communication Communications systems Defects Disabled-1 protein Docking Embryos Endothelial cells Endothelium Extracellular matrix Filopodia Glycoproteins Growth factors Homeostasis Individualized Instruction Integrity Laminin Membrane permeability Mice Migration Nervous system Networks Neural networks Neuronal-glial interactions Neurons Nutrients Permeability Receptors Retina Secretion Stimuli Vascular endothelial growth factor Vascular system |
| title | Endothelial Dab1 signaling orchestrates neuro-glia-vessel communication in the central nervous system |
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