Radial Glial Cell-Derived VCAM1 Regulates Cortical Angiogenesis Through Distinct Enrichments in the Proximal and Distal Radial Processes.

Publisher: Oxford University Press Country of Publication: United States NLM ID: 9110718 Publication Model: Print Cited Medium: Internet ISSN: 1460-2199 (Electronic) Linking ISSN: 10473211 NLM ISO Abbreviation: Cereb Cortex Subsets: MEDLINE

Original Publication: New York, NY : Oxford University Press, c1991-

Cell Proliferation/*genetics ; Cerebral Cortex/*embryology ; Endothelial Cells/*metabolism ; Ependymoglial Cells/*metabolism ; Neovascularization, Physiologic/*genetics ; Vascular Cell Adhesion Molecule-1/*genetics; Animals ; Cell Proliferation/drug effects ; Cerebral Cortex/blood supply ; Cerebral Ventricles/blood supply ; Cerebral Ventricles/embryology ; Endothelial Cells/cytology ; Ependymoglial Cells/drug effects ; Gene Knockdown Techniques ; In Vitro Techniques ; Mice ; Mice, Knockout ; Neovascularization, Physiologic/drug effects ; Vascular Cell Adhesion Molecule-1/drug effects ; Vascular Cell Adhesion Molecule-1/metabolism

Angiogenesis in the developing cerebral cortex accompanies cortical neurogenesis. However, the precise mechanisms underlying cortical angiogenesis at the embryonic stage remain largely unknown. Here, we show that radial glia-derived vascular cell adhesion molecule 1 (VCAM1) coordinates cortical vascularization through different enrichments in the proximal and distal radial glial processes. We found that VCAM1 was highly enriched around the blood vessels in the inner ventricular zone (VZ), preventing the ingrowth of blood vessels into the mitotic cell layer along the ventricular surface. Disrupting the enrichment of VCAM1 surrounding the blood vessels by a tetraspanin-blocking peptide or conditional deletion of Vcam1 gene in neural progenitor cells increased angiogenesis in the inner VZ. Conversely, VCAM1 expressed in the basal endfeet of radial glial processes promoted angiogenic sprouting from the perineural vascular plexus (PNVP). In utero, overexpression of VCAM1 increased the vessel density in the cortical plate, while knockdown of Vcam1 accomplished the opposite. In vitro, we observed that VCAM1 bidirectionally affected endothelial cell proliferation in a concentration-dependent manner. Taken together, our findings identify that distinct concentrations of VCAM1 around VZ blood vessels and the PNVP differently organize cortical angiogenesis during late embryogenesis.
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Keywords: VCAM1; angiogenesis; cerebral cortex; neurogenesis; radial glial cell

0 (Vascular Cell Adhesion Molecule-1)

Date Created: 20200108 Date Completed: 20211220 Latest Revision: 20211220

20221213

10.1093/cercor/bhz337

31907535