ArticleThe Journal of clinical investigation2020
Lack of Flvcr2 impairs brain angiogenesis without affecting the blood-brain barrier.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 24 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Cellular and signalling mechanisms that regulate the blood-brain barrier.Nature reviews. Molecular cell biology · 2026Review
- FLVCR2 Regulation of Intracellular Heme Modulates Vascular Tip/Stalk Specification During Retinal Angiogenesis.Investigative ophthalmology & visual science · 2026Article
- More than a ring: the emerging role of heme in angiogenesis.Cell communication and signaling : CCS · 2026Review
- CD98hc controls CNS angiogenesis and blood-brain barrier integrity through localized regulation of the systemic integrin-FAK pathway.Nature cardiovascular research · 2026Article
- A hypomorphic FLVCR2 variant resulting in moderate transport deficiency causes hydranencephaly syndrome with brain calcifications.European journal of human genetics : EJHG · 2026Article
- Development of the blood-brain barrier.Development (Cambridge, England) · 2026Review
- Altered brain vascularization and transcriptional changes in embryos lacking ABCA1 support a role of cholesterol in brain angiogenesis.Frontiers in cell and developmental biology · 2026Article
- Arteriovenous Malformations (AVMs): Molecular Pathogenesis, Clinical Features, and Emerging Therapeutic Strategies.Biomolecules · 2025Review
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- Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus.Cell reports. Medicine · 2024Article
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- Shared Genetic Features of Psoriasis and Myocardial Infarction: Insights From a Weighted Gene Coexpression Network Analysis.Journal of the American Heart Association · 2024Article
- MFSD7c functions as a transporter of choline at the blood-brain barrier.Cell research · 2024Article
- Integrative genetic analysis identifies FLVCR1 as a plasma-membrane choline transporter in mammals.Cell metabolism · 2023Article
- Opportunities and limitations for studying neuropsychiatric disorders using patient-derived induced pluripotent stem cells.Molecular psychiatry · 2023Review
- Congenital hydrocephalus: new Mendelian mutations and evidence for oligogenic inheritance.Human genomics · 2023Article
- Molecular Mechanisms of Iron and Heme Metabolism.Annual review of nutrition · 2022Review
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Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Fowler syndrome is a rare autosomal recessive brain vascular disorder caused by mutation in FLVCR2 in humans. The disease occurs during a critical period of brain vascular development, is characterized by glomeruloid vasculopathy and hydrocephalus, and is almost invariably prenatally fatal. Here, we sought to gain insights into the process of brain vascularization and the pathogenesis of Fowler syndrome by inactivating Flvcr2 in mice. We showed that Flvcr2 was necessary for angiogenic sprouting in the brain, but surprisingly dispensable for maintaining the blood-brain barrier. Endothelial cells lacking Flvcr2 had altered expression of angiogenic factors, failed to adopt tip cell properties, and displayed reduced sprouting, leading to vascular malformations similar to those seen in humans with Fowler syndrome. Brain hypovascularization was associated with hypoxia and tissue infarction, ultimately causing hydrocephalus and death of mutant animals. Strikingly, despite severe vascular anomalies and brain tissue infarction, the blood-brain barrier was maintained in Flvcr2 mutant mice. Our Fowler syndrome model therefore defined the pathobiology of this disease and provided new insights into brain angiogenesis by showing uncoupling of vessel morphogenesis and blood-brain barrier formation.
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What OpenQuestion holds
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.