ArticleDevelopmental biology2015
The role of folate metabolism in orofacial development and clefting.
Article in Developmental biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- A Combination of Variants in SEPTIN9 and MSX1 Genes Leads to the Formation of Orofacial Clefts.Genes to cells : devoted to molecular & cellular mechanisms · 2026Article
- Global, regional, and national burden and trends of congenital birth defects from 1990 to 2021: epidemiological trends, health inequalities, and COVID-19 impact.Translational pediatrics · 2026Article
- Recent Developments in Single-Cell Metabolomics by Mass Spectrometry─A Perspective.Journal of proteome research · 2025Review
- Molecular Regulation of Palatogenesis and Clefting: An Integrative Analysis of Genetic, Epigenetic Networks, and Environmental Interactions.International journal of molecular sciences · 2025Review
- TheFrontiers in medicine · 2025Review
- Dyrk1a is required for craniofacial development in Xenopus laevis.Developmental biology · 2024Article
- Wnt/BMP Mediated Metabolic Reprogramming Preserves Multipotency of Neural Crest-Like Stem Cells.Stem cells (Dayton, Ohio) · 2023Article
- Genome-wide analysis of copy-number variation in humans with cleft lip and/or cleft palate identifies COBLL1, RIC1, and ARHGEF38 as clefting genes.American journal of human genetics · 2023Article
- Parental folate deficiency induces birth defects in mice accompanied with increased de novo mutations.Cell discovery · 2022Article
- E-liquids and vanillin flavoring disrupts retinoic acid signaling and causes craniofacial defects in Xenopus embryos.Developmental biology · 2022Article
- Folate Carrier Deficiency Drives Differential Methylation and Enhanced Cellular Potency in the Neural Plate Border.Frontiers in cell and developmental biology · 2022Article
- Low maternal vitamin A intake increases the incidence of teratogen induced congenital diaphragmatic hernia in mice.Pediatric research · 2022Article
- Neural crest metabolism: At the crossroads of development and disease.Developmental biology · 2021Review
- Using an aquatic model, Xenopus laevis, to uncover the role of chromodomain 1 in craniofacial disorders.Genesis (New York, N.Y. : 2000) · 2021Article
- Epigenetic Regulation of Cardiac Neural Crest Cells.Frontiers in cell and developmental biology · 2021Review
- Environmental mechanisms of orofacial clefts.Birth defects research · 2020Review
- Role of epigenetics and miRNAs in orofacial clefts.Birth defects research · 2020Review
- Extremity Findings of Methotrexate Embryopathy.Hand (New York, N.Y.) · 2020Article
- Humans and Chimpanzees Display Opposite Patterns of Diversity inG3 (Bethesda, Md.) · 2019Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Folate deficiency has been associated with numerous diseases and birth defects including orofacial defects. However, whether folate has a role in the face during early orofacial development has been unclear. The present study reveals that pharmacological and antisense oligonucleotide mediated inhibition of DHFR, an integral enzyme in the folate pathway, results in specific changes in the size and shape of the midface and embryonic mouth. Such defects are accompanied by a severe reduction in the muscle and cartilage jaw elements without significant change in neural crest pattern or global levels of methylation. We propose that the orofacial defects associated with DHFR deficient function are the result of decreased cell proliferation and increased cell death via DNA damage. In particular, localized apoptosis may also be depleting the cells of the face that express crucial genes for the differentiation of the jaw structures. Folate supplementation is widely known to reduce human risk for orofacial clefts. In the present study, we show that activating folate metabolism can reduce median oral clefts in the primary palate by increasing cell survival. Moreover, we demonstrate that a minor decrease in DHFR function exacerbates median facial clefts caused by RAR inhibition. This work suggests that folate deficiencies could be a major contributing factor to multifactorial orofacial defects.
Indexed as
Identifiers
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.