ArticleThe Journal of clinical investigation2020
Deficiency of MFSD7c results in microcephaly-associated vasculopathy in Fowler syndrome.
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.
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Who cites it
22 citing papers in PubMed, 25 citations in OpenAlex.
- 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
- 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
- Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- Molecular Mechanisms of Iron Metabolism and Overload.Biomedicines · 2025Review
- Cellular and organismal function of choline metabolism.Nature metabolism · 2025Review
- Endothelial Myosin IIA Is Required for the Maintenance of Blood-Brain Barrier Integrity.Cells · 2024Article
- MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis.Nature communications · 2024Article
- Update on heme biosynthesis, tissue-specific regulation, heme transport, relation to iron metabolism and cellular energy.Liver international : official journal of the International Association for the Study of the Liver · 2024Review
- Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus.Cell reports. Medicine · 2024Article
- Article
- Article
- 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
- Glutaminolysis and the Control of Neural Progenitors in Neocortical Development and Evolution.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2023Review
- Causes of microcephaly in human-theoretical considerations.Frontiers in neuroscience · 2023Article
- Molecular Mechanisms of Iron and Heme Metabolism.Annual review of nutrition · 2022Review
- The glycolytic process in endothelial cells and its implications.Acta pharmacologica Sinica · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several missense mutations in the orphan transporter FLVCR2 have been reported in Fowler syndrome. Affected subjects exhibit signs of severe neurological defects. We identified the mouse ortholog Mfsd7c as a gene expressed in the blood-brain barrier. Here, we report the characterizations of Mfsd7c-KO mice and compare these characterizations to phenotypic findings in humans with biallelic FLVCR2 mutations. Global KO of Mfsd7c in mice resulted in late-gestation lethality, likely due to CNS phenotypes. We found that the angiogenic growth of CNS blood vessels in the brain of Mfsd7c-KO embryos was inhibited in cortical ventricular zones and ganglionic eminences. Vascular tips were dilated and fused, resulting in glomeruloid vessels. Nonetheless, CNS blood vessels were intact, without hemorrhage. Both embryos and humans with biallelic FLVCR2 mutations exhibited reduced cerebral cortical layers, enlargement of the cerebral ventricles, and microcephaly. Transcriptomic analysis of Mfsd7cK-KO embryonic brains revealed upregulation of genes involved in glycolysis and angiogenesis. The Mfsd7c-KO brain exhibited hypoxia and neuronal cell death. Our results indicate that MFSD7c is required for the normal growth of CNS blood vessels and that ablation of this gene results in microcephaly-associated vasculopathy in mice and humans.
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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.