GPR124, an orphan G protein-coupled receptor, is required for CNS-specific vascularization and establishment of the blood-brain barrier

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 14; pp. 5759 - 5764
• Main Authors: Cullen, Mike, Elzarrad, Mohammed K, Seaman, Steven, Zudaire, Enrique, Stevens, Janine, Yang, Mi Young, Li, Xiujie, Chaudhary, Amit, Xu, Lihong, Hilton, Mary Beth, Logsdon, Daniel, Hsiao, Emily, Stein, Erica V, Cuttitta, Frank, Haines, Diana C, Nagashima, Kunio, Tessarollo, Lino, St. Croix, Brad
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 05.04.2011; National Acad Sciences
• Subjects: adhesion; Angiogenesis; Animals; Biological Sciences; Blood brain barrier; Blood vessels; Blood-Brain Barrier - embryology; Blood-Brain Barrier - metabolism; Blotting, Western; Brain; Central nervous system; Central Nervous System - blood supply; Central Nervous System - embryology; cerebral cortex; Cerebrovascular diseases; cerebrovascular disorders; Cortex; DNA Primers - genetics; Drug development; drugs; Embryo, Mammalian - blood supply; Embryo, Mammalian - metabolism; Embryos; Endothelial cells; Flow Cytometry; Forebrain; G protein-coupled receptors; Histological Techniques; In Situ Hybridization; Lethality; Mice; Microscopy, Electron; Microscopy, Fluorescence; Migration; Neurons; Nutrients; Oxygen; Proteins; Receptors; Receptors, G-Protein-Coupled - physiology; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Spinal cord; Tumors; vascularization
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1017192108

Every organ in the body requires blood vessels for efficient delivery of oxygen and nutrients, but independent vascular beds are highly specialized to meet the individual needs of specific organs. The vasculature of the brain is tightly sealed, with blood-brain barrier (BBB) properties developing coincident with neural vascularization. G protein-coupled receptor 124 (GPR124) (tumor endothelial marker 5, TEM5), an orphan member of the adhesion family of G protein-coupled receptors, was previously identified on the basis of its overexpression in tumor vasculature. Here, we show that global deletion or endothelial-specific deletion of GPR124 in mice results in embryonic lethality associated with abnormal angiogenesis of the forebrain and spinal cord. Expression of GPR124 was found to be required for invasion and migration of blood vessels into neuroepithelium, establishment of BBB properties, and expansion of the cerebral cortex. Thus, GPR124 is an important regulator of neurovasculature development and a potential drug target for cerebrovascular diseases.