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

  1. Author:
    Cullen, M.
    Elzarrad, M. K.
    Seaman, S.
    Zudaire, E.
    Stevens, J.
    Yang, M. Y.
    Li, X. J.
    Chaudhary, A.
    Xu, L. H.
    Hilton, M. B.
    Logsdon, D.
    Hsiao, E.
    Stein, E. V.
    Cuttitta, F.
    Haines, D. C.
    Nagashima, K.
    Tessarollo, L.
    St Croix, B.

  2. Author Address

    [Cullen, M Cullen, M; Elzarrad, MK; Seaman, S; Stevens, J; Yang, MY; Li, XJ; Chaudhary, A; Xu, LH; Hilton, MB; Hsiao, E; Stein, EV; St Croix, B] NCI, Tumor Angiogenesis Sect, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA [Zudaire, E; Cuttitta, F] NCI, Angiogenesis Core Facil, NIH, Gaithersburg, MD 20877 USA [Hilton, MB; Logsdon, D] NCI, Basic Res Program, Frederick, MD 21702 USA [Haines, DC] NCI, Vet Pathol Sect, Pathol Histotechnol Lab, Frederick, MD 21702 USA [Nagashima, K] NCI, Image Anal Lab, Adv Technol Program, Sci Applicat Int Corp, Frederick, MD 21702 USA [Tessarollo, L] NCI, Neural Dev Sect, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA;St Croix, B (reprint author), NCI, Tumor Angiogenesis Sect, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA;stcroix@ncifcrf.gov
    1. Year: 2011
    2. Date: Apr
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 108
    2. 14
    3. Pages: 5759-5764
  4. Type of Article: Article
  5. ISSN: 0027-8424
  1. 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.

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External Sources

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  2. DOI: 10.1073/pnas.1017192108
  3. View record in Web of Science®
  4. WOS: 000289265300053

Library Notes

  1. Fiscal Year: FY2010-2011
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