title: GPR124, an orphan G protein-coupled receptor, is required for CNS-specific vascularization and establishment of the blood-brain barrier.
abstract: 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.
authors.affiliation: Tumor Angiogenesis Section, Mouse Cancer Genetics Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Cullen
authors.forename: Mohammed K
authors.initials: MK
authors.lastname: Elzarrad
authors.forename: Steven
authors.initials: S
authors.lastname: Seaman
authors.forename: Enrique
authors.initials: E
authors.lastname: Zudaire
authors.forename: Janine
authors.initials: J
authors.lastname: Stevens
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Yang
authors.forename: Xiujie
authors.initials: X
authors.lastname: Li
authors.forename: Amit
authors.initials: A
authors.lastname: Chaudhary
authors.forename: Lihong
authors.initials: L
authors.lastname: Xu
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Hilton
authors.forename: Daniel
authors.initials: D
authors.lastname: Logsdon
authors.forename: Emily
authors.initials: E
authors.lastname: Hsiao
authors.forename: Erica V
authors.initials: EV
authors.lastname: Stein
authors.forename: Frank
authors.initials: F
authors.lastname: Cuttitta
authors.forename: Diana C
authors.initials: DC
authors.lastname: Haines
authors.forename: Kunio
authors.initials: K
authors.lastname: Nagashima
authors.forename: Lino
authors.initials: L
authors.lastname: Tessarollo
authors.forename: Brad
authors.initials: B
authors.lastname: St Croix
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000196:embryology* / Q000378:metabolism; D015153:Blotting, Western; D002490:Central Nervous System / Q000098:blood supply* / Q000196:embryology*; D017931:DNA Primers / Q000235:genetics; D004622:Embryo, Mammalian / Q000098:blood supply* / Q000378:metabolism; D005434:Flow Cytometry; D006652:Histological Techniques; D017403:In Situ Hybridization; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; C554106:GPR124 protein, mouse; D043562:Receptors, G-Protein-Coupled