Folic acid has been shown to have a protective effect against neurocristopathic malformations resulted from neural crest defects. However, the mechanism behind is largely unknown. The recent work by Dr. MAO Bing-yu’s group ( Kunming Institute of Zoology, Chinese Academy of Sciences) revealed that the folate metabolism pathway might regulate neural crest development epigenetically (Li et al., PLoS ONE 6(11): e27198.).

Reduced folate carrier (RFC) is a membrane transporter for reduced folate. In Xenopus embryos, RFC is specifically expressed in neural crest tissues and knockdown of RFC results in severe neurocristopathies. Inhibition of RFC blocked the expression of a series of neural crest marker genes while overexpression of RFC or injection of 5-methyltetrahydrofolate expanded the neural crest territories. In animal cap assays, knockdown of RFC dramatically reduced the mono- and trimethyl-Histone3-K4 levels and co-injection of the lysine methyltransferase hMLL1 largely rescued the XRFC morpholino phenotype. These data revealed that the RFC mediated folate metabolic pathway likely potentiates neural crest gene expression through epigenetic modifications and manifests the role of nutrients in gene transcriptional regulation through epigenetic modification.