Cited by 303Angiogenesis and VEGF in CancerBarrier Structure and Function StudiesNeurogenesis and neuroplasticity mechanisms

Essential Regulation of CNS Angiogenesis by the Orphan G Protein–Coupled Receptor GPR124

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Kuhnert, Frank, Mancuso, Michael R., Shamloo, Amir, Wang, Hsiao-Ting, Choksi, Vir, Florek, Mareike, Su, Hua, Fruttiger, Marcus +3 more·2010·Science

Abstract

The orphan G protein-coupled receptor (GPCR) GPR124/tumor endothelial marker 5 is highly expressed in central nervous system (CNS) endothelium. Here, we show that complete null or endothelial-specific GPR124 deletion resulted in embryonic lethality from CNS-specific angiogenesis arrest in forebrain and neural tube. Conversely, GPR124 overexpression throughout all adult vascular beds produced CNS-specific hyperproliferative vascular malformations. In vivo, GPR124 functioned cell-autonomously in endothelium to regulate sprouting, migration, and developmental expression of the blood-brain barrier marker Glut1, whereas in vitro, GPR124 mediated Cdc42-dependent directional migration to forebrain-derived, vascular endothelial growth factor-independent cues. Our results demonstrate CNS-specific angiogenesis regulation by an endothelial receptor and illuminate functions of the poorly understood adhesion GPCR subfamily. Further, the functional tropism of GPR124 marks this receptor as a therapeutic target for CNS-related vascular pathologies.

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Crossref · 10.1126/science.1196554

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  • Wnt signaling pathway including Wnt ligands, Norrins, Frizzled receptors, Lrp5/6 coreceptors, Gpr124 and Reck cofactors, and β-catenin are critical for both vascular development and barriergenesis.

    “Wnt signaling pathway including Wnt ligands, Norrins, Frizzled receptors, Lrp5/6 coreceptors, Gpr124 and Reck cofactors, and 𝛃 -catenin are critical for both vascular development and barriergenesis (138, 332, 558, 636, 682, 689);”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [332]

    The paper’s Abstract reports that GPR124 is essential for embryonic CNS angiogenesis and regulates expression of Glut1, a blood–brain barrier marker. It does not establish GPR124 as part of the Wnt pathway or prove a role in barriergenesis: it says GPR124 may act in a pathway parallel to β-catenin and describes broader BBB functions as a subject for future investigation. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Authors
Kuhnert, F., Mancuso, M. R., Shamloo, A., Wang, H.-T., Choksi, V., Florek, M., Su, H., Fruttiger, M., Young, W. L., Heilshorn, S. C., & Kuo, C. J.
Affiliations
  • Stanford Medicine (US)
  • Stanford University (US)
  • University of California, San Francisco (US)
  • University College London (GB)
Corresponding author
Kuo, Calvin J.
Venue
Science
Published
2010-11-12
Volume
330
Issue
6006
Pages
985-989
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2115716038
Cited by
301
References
32
Citations by year
2026: 11 · 2025: 16 · 2024: 17 · 2023: 16 · 2022: 29 · 2021: 23 · 2020: 17 · 2019: 21 · 2018: 18 · 2017: 20 · 2016: 20 · 2015: 19 · 2014: 22 · 2013: 16 · 2012: 20
FWCI
6.78
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • National Institutes of Health (5r21ns058600-02, 1dp2od006477-01)
  • National Heart, Lung, and Blood Institute (R01HL074267)
  • National Cancer Institute (R01CA095654, T32CA009302)
  • National Institute of General Medical Sciences (T32GM007365, GM 07365)
  • National Institute of Neurological Disorders and Stroke (1R21 NS058600, P01NS044155, R01NS027713, R01NS052830, P01 NS 44155, R01NS064517, R01-NS 27713, R21 NS058600, R21NS070153)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
GPR124, orphan G protein-coupled receptor, adhesion GPCRs, endothelial cells, embryonic lethality, neural tube, forebrain, vascular malformations, Cdc42, endothelial cell migration, sprouting angiogenesis, blood-brain barrier, GLUT1
MeSH terms
Animals, Blood Vessels, Blood-Brain Barrier, Cell Movement, Endothelium, Vascular, Mesencephalon, Mice, Transgenic, Rhombencephalon, Telencephalon, Prosencephalon, Gene Deletion, Mice, Knockout, Neovascularization, Physiologic, Endothelial Cells, Receptors, G-Protein-Coupled, Embryonic Development, Glucose Transporter Type 1, Mice, Neural Tube

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