ArticleProceedings of the National Academy of Sciences of the United States of America2011
Angiogenic sprouting into neural tissue requires Gpr124, an orphan G protein-coupled receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 152 citations in OpenAlex.
- The extracellular matrix as a dynamic regulator of brain function and plasticity.Neurobiology of disease · 2026Review
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- The GPR124‑Wnt‑PPARγ regulatory axis: Molecular mechanisms and therapeutic implications in chronic inflammatory diseases (Review).International journal of molecular medicine · 2026Review
- Development of the blood-brain barrier.Development (Cambridge, England) · 2026Review
- Adhesion G-Protein Coupled Receptors in Neurological and Psychiatric Disorders.Journal of psychiatry and brain science · 2025Article
- Spatiotemporal profiling of adhesion G protein-coupled receptors in developing mouse and human pancreas reveals a role for GPR56 in islet development.Cellular and molecular life sciences : CMLS · 2025Article
- Activation of Wnt/β-catenin in neural progenitor cells regulates blood-brain barrier development and promotes neuroinflammation.Scientific reports · 2025Article
- An Alternative Mode of GPCR Transactivation: Activation of GPCRs by Adhesion GPCRs.International journal of molecular sciences · 2025Review
- Potential role of G protein‑coupled receptor 124 in cardiovascular and cerebrovascular disease (Review).Experimental and therapeutic medicine · 2025Review
- Single-cell atlas of the human brain vasculature across development, adulthood and disease.Nature · 2024Article
- Signaling Role of Pericytes in Vascular Health and Tissue Homeostasis.International journal of molecular sciences · 2024Review
- GPR124 regulates murine brain embryonic angiogenesis and BBB formation by an intracellular domain-independent mechanism.Development (Cambridge, England) · 2024Article
- IL-1β disrupts the initiation of blood-brain barrier development by inhibiting endothelial Wnt/β-catenin signaling.iScience · 2024Article
- Thermosensitive hydrogel-based GPR124 delivery strategy for rebuilding blood-spinal cord barrier.Bioengineering & translational medicine · 2023Article
- Shaping the brain vasculature in development and disease in the single-cell era.Nature reviews. Neuroscience · 2023Review
- Regulation of the Blood-Brain Barrier in Health and Disease.Cold Spring Harbor perspectives in medicine · 2023Article
- Brain endothelial cells acquire blood-brain barrier properties in the absence of Vegf-dependent CNS angiogenesis.Developmental biology · 2023Article
- Transgenic animal models to explore and modulate the blood brain and blood retinal barriers of the CNS.Fluids and barriers of the CNS · 2022Review
- Adhesion G protein-coupled receptors: structure, signaling, physiology, and pathophysiology.Physiological reviews · 2022Review
- Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The vasculature of the CNS is structurally and functionally distinct from that of other organ systems and is particularly prone to developmental abnormalities and hemorrhage. Although other embryonic tissues undergo primary vascularization, the developing nervous system is unique in that it is secondarily vascularized by sprouting angiogenesis from a surrounding perineural plexus. This sprouting angiogenesis requires the TGF-β and Wnt pathways because ablation of these pathways results in aberrant sprouting and hemorrhage. We have genetically deleted Gpr124, a member of the large family of long N-terminal group B G protein-coupled receptors, few members of which have identified ligands or well-defined biologic functions in mammals. We show that, in the developing CNS, Gpr124 is specifically expressed in the vasculature and is absolutely required for proper angiogenic sprouting into the developing neural tube. Embryos lacking Gpr124 exhibit vascular defects characterized by delayed vascular penetration, formation of pathological glomeruloid tufts within the CNS, and hemorrhage. In addition, they display defects in palate and lung development, two processes in which TGF-β and/or Wnt pathways also play important roles. We also show that TGF-β stimulates Gpr124 expression, and ablation of Gpr124 results in perturbed TGF-β pathway activation, suggesting roles for Gpr124 in modulating TGF-β signaling. These results represent a unique function attributed to a long N-terminal group B-type G protein-coupled receptor in a mammalian system.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.