Folate receptors and neural tube closure.
Neural tube defects (NTD) are among the most common human congenital malformations, affecting 0.5-8.0/1000 of live births. Human clinical trials have shown that periconceptional folate supplementation significantly decreases the occurrence of NTD in offspring. However, the mechanism by which folate acts on NTD remains largely unknown. Folate receptor (Folr) is one of the three membrane proteins that mediate cellular uptake of folates. Recent studies suggest that mouse Folr1 (formerly referred to as Fbp1) is essential for neural tube closure. Therefore, we examined spatial and temporal expression patterns of Folr1 in developing mouse embryos, showing a close association between Folr1 and anterior neural tube closure. Transient transgenic analysis was performed using lacZ as a reporter; we identified a 1.1-kb enhancer that directs lacZ expression in the neural tube and optic vesicle in a manner that is similar to endogenous Folr1. The 1.1-kb enhancer sequences were highly conserved between humans and mice, suggesting that human FOLR1 is associated with anterior neural tube closure in humans. Several experimental studies in mice and human epidemiological and genetics studies have suggested that folate receptor abnormalities are involved in a portion of human NTDs, although the solo defect of FOLR1 did not cause NTD.
['Saitsu|Hirotomo|H|http://orcid.org/0000-0003-0723-0960']
D000818:Animals D004622:Embryo, Mammalian D004742:Enhancer Elements, Genetic D005260:Female D058975:Folate Receptor 1 D005492:Folic Acid D018507:Gene Expression Regulation, Developmental D017930:Genes, Reporter D006801:Humans D007763:Lac Operon D051379:Mice D008822:Mice, Transgenic D054259:Neural Tube D009436:Neural Tube Defects
folate receptor neural tube defect FOLR1 FOLR1 Folr1