ArticleProceedings of the National Academy of Sciences of the United States of America2018
Interplay of the Norrin and Wnt7a/Wnt7b signaling systems in blood-brain barrier and blood-retina barrier development and maintenance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 110 papers.
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Who cites it
110 citing papers in PubMed, 166 citations in OpenAlex.
- Role of the WNT signalling pathway in physiological and pathological blood-brain barrier.Annals of medicine · 2026Review
- 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
- Receptor tyrosine kinase signaling in mammalian eye development.Developmental biology · 2026Review
- Cellular and signalling mechanisms that regulate the blood-brain barrier.Nature reviews. Molecular cell biology · 2026Review
- Article
- The calcium pump ATP2B1/PMCA1 regulates CNS vascular development by facilitating Norrin- and WNT7A/B-induced Frizzled4 signaling.Cell reports · 2026Article
- Laser interstitial thermal therapy enhances bidirectional blood-brain barrier permeability in glioblastoma.Neuro-oncology · 2026Article
- GPR124 regulates hyaloid blood vessel regression and is associated with endothelial-mesenchymal transition.Scientific reports · 2026Article
- Luminal surface proteome of the brain vasculature uncovers blood-brain barrier regulators.Science (New York, N.Y.) · 2026Article
- FRZB-induced anti-angiogenic effect via Caveolin-1-mediated TGFβ signalling.Nature communications · 2026Article
- A FZD4/LRP5 agonist restores pericyte coverage and vascular integrity by increasing PDGFB signaling.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms of parasite-mediated disruption of brain vessels.FEBS letters · 2026Review
- The crosstalk between blood-brain barrier and neural cells: bidirectional regulation of brain function and pathology.Biochemistry and biophysics reports · 2026Review
- Müller cell glutamine metabolism links photoreceptor and endothelial injury in diabetic retinopathy.Life science alliance · 2026Article
- Endothelial PROX1 induces blood-brain barrier disruption in the central nervous system.JCI insight · 2026Article
- Article
- HaloTrace: A spatiotemporally precise fluorescent readout of blood-brain barrier permeability in mice.bioRxiv : the preprint server for biology · 2025Article
- Regional heterogeneity of the blood-brain barrier.Nature communications · 2025Article
- The MDM2-p53 axis regulates norrin/frizzled4 signaling and blood-CNS barrier function.Science signaling · 2025Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
β-Catenin signaling controls the development and maintenance of the blood-brain barrier (BBB) and the blood-retina barrier (BRB), but the division of labor and degree of redundancy between the two principal ligand-receptor systems-the Norrin and Wnt7a/Wnt7b systems-are incompletely defined. Here, we present a loss-of-function genetic analysis of postnatal BBB and BRB maintenance in mice that shows striking threshold and partial redundancy effects. In particular, the combined loss of Wnt7a and Norrin or Wnt7a and Frizzled4 (Fz4) leads to anatomically localized BBB defects that are far more severe than observed with loss of Wnt7a, Norrin, or Fz4 alone. In the cerebellum, selective loss of Wnt7a in glia combined with ubiquitous loss of Norrin recapitulates the phenotype observed with ubiquitous loss of both Wnt7a and Norrin, implying that glia are the source of Wnt7a in the cerebellum. Tspan12, a coactivator of Norrin signaling in the retina, is also active in BBB maintenance but is less potent than Norrin, consistent with a model in which Tspan12 enhances the amplitude of the Norrin signal in vascular endothelial cells. Finally, in the context of a partially impaired Norrin system, the retina reveals a small contribution to BRB development from the Wnt7a/Wnt7b system. Taken together, these experiments define the extent of CNS region-specific cooperation for several components of the Norrin and Wnt7a/Wnt7b systems, and they reveal substantial regional heterogeneity in the extent to which partially redundant ligands, receptors, and coactivators 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.