ArticleMechanisms of development2018
Valproic acid disrupts the biomechanics of late spinal neural tube closure in mouse embryos.
Article in Mechanisms of development, 2018. 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, 32 citations in OpenAlex.
- Self-organized anteroposterior regionalization of early midbrain and hindbrain/spinal cords using micropatterned human pluripotent stem cells.SLAS technology · 2026Article
- Protective Effect of myo-Inositol Against Decitabine-Induced Neural Tube Defects in Embryonic Zebrafish.Neurotoxicity research · 2025Article
- Valproic acid-induced teratogenicity is driven by senescence and prevented by Rapamycin in human spinal cord and animal models.Molecular psychiatry · 2025Article
- Toxicity assessment using neural organoids: innovative approaches and challenges.Toxicological research · 2025Review
- Diacylglycerol kinase γ facilitates the proliferation and migration of neural stem cells in the developing neural tube.Acta biochimica et biophysica Sinica · 2024Article
- Gestational Fisetin Exerts Neuroprotection by Regulating Mitochondria-Directed Canonical Wnt Signaling, BBB Integrity, and Apoptosis in Prenatal VPA-Induced Rodent Model of Autism.Molecular neurobiology · 2024Article
- RosetteArraybioRxiv : the preprint server for biology · 2024Article
- The incorporation of MALDI mass spectrometry imaging in studies to identify markers of toxicity followingFrontiers in toxicology · 2024Article
- Transcriptional Signature of Valproic Acid-Induced Neural Tube Defects in Human Spinal Cord Organoids.International journal of stem cells · 2023Article
- Cannabidiol impairs neural tube closure in mouse whole embryo culture.Birth defects research · 2022Article
- Article
- Production of human spinal-cord organoids recapitulating neural-tube morphogenesis.Nature biomedical engineering · 2022Article
- Two-Photon Cell and Tissue Level Laser Ablation Methods to Study Morphogenetic Biomechanics.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Folic Acid Rescues Valproic Acid-Induced Morphogenesis Inhibition in Neural Rosettes Derived From Human Pluripotent Stem Cells.Frontiers in cellular neuroscience · 2022Article
- Antiseizure medication in early nervous system development. Ion channels and synaptic proteins as principal targets.Frontiers in pharmacology · 2022Review
- Embryo-derived teratoma in vitro biological system reveals antitumor and embryotoxic activity of valproate.The FEBS journal · 2020Article
- Refinement of inducible gene deletion in embryos of pregnant mice.Birth defects research · 2020Article
- Dynamic acetylation profile during mammalian neurulation.Birth defects research · 2020Article
- Probing disrupted neurodevelopment in autism using human stem cell-derived neurons and organoids: An outlook into future diagnostics and drug development.Developmental dynamics : an official publication of the American Association of Anatomists · 2020Review
- Mouse whole embryo culture: Evaluating the requirement for rat serum as culture medium.Birth defects research · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Failure of neural tube closure in the early embryo causes neural tube defects including spina bifida. Spina bifida lesions predominate in the distal spine, particularly after exposure to the anticonvulsant valproic acid (VPA). How VPA specifically disturbs late stages of neural tube closure is unclear, as neurulation is usually viewed as a uniform 'zippering' process along the spine. We recently identified a novel closure site ("Closure 5") which forms at the caudal extremity of the mouse posterior neuropore (PNP) when completion of closure is imminent. Here we investigated whether distal spina bifida in VPA-exposed embryos involves disruption of Closure 5. Exposure of E8.5 mouse embryos to VPA in whole embryo culture had marked embryotoxic effects, whereas toxic effects were less pronounced in more developmentally advanced (E9) embryos. Only 33% of embryos exposed to VPA from E9 to E10.5 achieved PNP closure (control=90%). Short-term (8h) VPA treatment diminished supra-cellular F-actin cables which normally run along the lateral neural folds, and prevented caudal PNP narrowing normally characteristic of Closure 5 formation. Laser ablation of Closure 5 caused rapid neuropore widening. Equivalent ablations of the caudal PNP in VPA treated embryos resulted in significantly less widening, suggesting VPA prevents formation of Closure 5 as a biomechanically active structure. Thus, VPA exposure prevents morphological and biomechanical conversion of the caudal extreme of the PNP during late spinal closure. Closure 5 facilitates neural fold apposition when completion of closure is imminent, such that its disruption in VPA-exposed embryos may lead to distal spina bifida.
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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.