ArticleThe Journal of clinical investigation2014
Canonical WNT signaling components in vascular development and barrier formation.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 230 papers, 1 of them a synthesis that pooled it.
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Who cites it
230 citing papers in PubMed, 1 synthesis or guideline pooled it, 344 citations in OpenAlex.
- The Role of Clusterin Transporter in the Pathogenesis of Alzheimer's Disease at the Blood-Brain Barrier Interface: A Systematic Review.Biomolecules · 2022Pooled it
- Role of the WNT signalling pathway in physiological and pathological blood-brain barrier.Annals of medicine · 2026Review
- Fibulin-1 is required for microvascular integrity in the developing brain and retina.Developmental biology · 2026Article
- Architecture of the Norrin signaling complex and structure-guided surrogate design.Nature structural & molecular biology · 2026Article
- Wnt Pathway Agonism as a Therapeutic Strategy for Retinal Vascular Diseases: A Narrative Review of Evidence to Date.Ophthalmology and therapy · 2026Review
- AAV-norrin gene therapy rescues retinal defects in mice with Norrie disease and oxygen-induced retinopathy.Molecular therapy. Advances · 2026Article
- Cellular and signalling mechanisms that regulate the blood-brain barrier.Nature reviews. Molecular cell biology · 2026Review
- Biomedical Materials and Fabrication Methods for Construction of In Vitro Neurovascular Unit Models.Materials (Basel, Switzerland) · 2026Review
- Expanding roles of N-glycosylation in the endoplasmic reticulum.Trends in cell biology · 2026Review
- Coronary endothelial cells undergo venous-enriched disrupted maturation following myocardial infarction.Basic research in cardiology · 2026Article
- Spatiotemporal arising of molecular and functional blood-brain barrier properties in the developing Gallus gallus optic tectum.Fluids and barriers of the CNS · 2026Article
- Myovascular Niche: The Role of Endothelial Cells in Skeletal Muscle Health and Disease.Circulation research · 2026Review
- Targeting CD4⁺ T cell infiltration: mechanisms and therapeutic insights into CD4⁺ T cell transmigration across the blood-brain barrier in acute ischemic stroke.Fluids and barriers of the CNS · 2026Review
- Neurovascular plasticity as a modulator of hypothalamic function.Reviews in endocrine & metabolic disorders · 2026Review
- Repeated TLR7 activation induces cell type- and brain region-specific transcriptome changes in male mice.Scientific reports · 2026Article
- Luminal surface proteome of the brain vasculature uncovers blood-brain barrier regulators.Science (New York, N.Y.) · 2026Article
- Intraocular pressure induced blood retinal barrier compromise in mouse models and human glaucoma.Nature communications · 2026Article
- A zebrafish multimodal toolbox to study the blood-brain barrier in health and disease.Scientific reports · 2026Article
- The GPR124‑Wnt‑PPARγ regulatory axis: Molecular mechanisms and therapeutic implications in chronic inflammatory diseases (Review).International journal of molecular medicine · 2026Review
- Mechanisms of parasite-mediated disruption of brain vessels.FEBS letters · 2026Review
170 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Canonical WNT signaling is required for proper vascularization of the CNS during embryonic development. Here, we used mice with targeted mutations in genes encoding canonical WNT pathway members to evaluate the exact contribution of these components in CNS vascular development and in specification of the blood-brain barrier (BBB) and blood-retina barrier (BRB). We determined that vasculature in various CNS regions is differentially sensitive to perturbations in canonical WNT signaling. The closely related WNT signaling coreceptors LDL receptor-related protein 5 (LRP5) and LRP6 had redundant functions in brain vascular development and barrier maintenance; however, loss of LRP5 alone dramatically altered development of the retinal vasculature. The BBB in the cerebellum and pons/interpeduncular nuclei was highly sensitive to decrements in canonical WNT signaling, and WNT signaling was required to maintain plasticity of barrier properties in mature CNS vasculature. Brain and retinal vascular defects resulting from ablation of Norrin/Frizzled4 signaling were ameliorated by stabilizing β-catenin, while inhibition of β-catenin-dependent transcription recapitulated the vascular development and barrier defects associated with loss of receptor, coreceptor, or ligand, indicating that Norrin/Frizzled4 signaling acts predominantly through β-catenin-dependent transcriptional regulation. Together, these data strongly support a model in which identical or nearly identical canonical WNT signaling mechanisms mediate neural tube and retinal vascularization and maintain the BBB and BRB.
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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.