ArticleProceedings of the National Academy of Sciences of the United States of America2013
Deletion of Mthfd1l causes embryonic lethality and neural tube and craniofacial defects in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. 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.
- Folate deficiency disrupts key metabolic transitions within the developing neural ectoderm.bioRxiv : the preprint server for biology · 2026Article
- Unravelling the Genetic Mechanisms of Litter Traits in a Maternal Line of Pigs.Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie · 2026Article
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- Integration of Metabolic Pathways and Micronutrient Signals Influences Neurodevelopment by Modulating Neural Stem Cell Dynamics.Molecular neurobiology · 2026Review
- Dual-stress-responsive-pathways prevent HCC initiation via p53 suppression of MTHFD1L-RNA mResearch square · 2026Article
- MTHFD1L in muscle invasive bladder cancer: a multi-cohort study on prognosis and therapeutic response.World journal of surgical oncology · 2026Article
- The role of metabolic reprogramming in oocyte development: research progress and prospects.Frontiers in reproductive health · 2026Review
- Classically activated macrophages undergo functionally significant nucleotide metabolism remodelling driven by nitric oxide.Nature metabolism · 2025Article
- SHMT2 is essential for mammalian preimplantation embryonic development throughMolecular therapy. Nucleic acids · 2025Article
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- Identification and verification of methylenetetrahydrofolate dehydrogenase 1-like protein as the binding target of natural product pseudolaric acid A.Natural products and bioprospecting · 2025Article
- The DNA demethylase TET1 modifies the impact of maternal folic acid status on embryonic brain development.EMBO reports · 2025Article
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- Brain development and bioenergetic changes.Neurobiology of disease · 2024Review
- Epigenetic regulation by TET1 in gene-environmental interactions influencing susceptibility to congenital malformations.bioRxiv : the preprint server for biology · 2024Article
- Optical coherence tomography-guided Brillouin microscopy highlights regional tissue stiffness differences during anterior neural tube closure in the Mthfd1l murine mutant.Development (Cambridge, England) · 2024Article
- Cycling back to folate metabolism in cancer.Nature cancer · 2024Review
- Targeted Treatment Strategies for Mitochondria Dysfunction: Correlation with Neurological Disorders.Current drug targets · 2024Review
- Exencephaly-Anencephaly Sequence Associated with Maxillary Brachygnathia, Spinal Defects, and Palatoschisis in a Male Domestic Cat.Animals : an open access journal from MDPI · 2023Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
Abstract
Maternal supplementation with folic acid is known to reduce the incidence of neural tube defects (NTDs) by as much as 70%. Despite the strong clinical link between folate and NTDs, the biochemical mechanisms through which folic acid acts during neural tube development remain undefined. The Mthfd1l gene encodes a mitochondrial monofunctional 10-formyl-tetrahydrofolate synthetase, termed MTHFD1L. This gene is expressed in adults and at all stages of mammalian embryogenesis with localized regions of higher expression along the neural tube, developing brain, craniofacial structures, limb buds, and tail bud. In both embryos and adults, MTHFD1L catalyzes the last step in the flow of one-carbon units from mitochondria to cytoplasm, producing formate from 10-formyl-THF. To investigate the role of mitochondrial formate production during embryonic development, we have analyzed Mthfd1l knockout mice. All embryos lacking Mthfd1l exhibit aberrant neural tube closure including craniorachischisis and exencephaly and/or a wavy neural tube. This fully penetrant folate-pathway mouse model does not require feeding a folate-deficient diet to cause this phenotype. Maternal supplementation with sodium formate decreases the incidence of NTDs and partially rescues the growth defect in embryos lacking Mthfd1l. These results reveal the critical role of mitochondrially derived formate in mammalian development, providing a mechanistic link between folic acid and NTDs. In light of previous studies linking a common splice variant in the human MTHFD1L gene with increased risk for NTDs, this mouse model provides a powerful system to help elucidate the specific metabolic mechanisms that underlie folate-associated birth defects, including NTDs.
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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.