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PLoS One 2011 Jan 01;611:e27198. doi: 10.1371/journal.pone.0027198.
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Xenopus reduced folate carrier regulates neural crest development epigenetically.

Li J , Shi Y , Sun J , Zhang Y , Mao B .

Folic acid deficiency during pregnancy causes birth neurocristopathic malformations resulting from aberrant development of neural crest cells. The Reduced folate carrier (RFC) is a membrane-bound receptor for facilitating transfer of reduced folate into the cells. RFC knockout mice are embryonic lethal and develop multiple malformations, including neurocristopathies. Here we show that XRFC is specifically expressed in neural crest tissues in Xenopus embryos and knockdown of XRFC by specific morpholino 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. Our data revealed that the RFC mediated folate metabolic pathway likely potentiates neural crest gene expression through epigenetic modifications.

PubMed ID: 22096536
PMC ID: PMC3212533
Article link: PLoS One

Species referenced: Xenopus laevis
Genes referenced: dvl2 foxd3 msx1 pax3 slc19a1 snai1 snai2 twist1 uqcc6 wnt7b zic1
Morpholinos: slc19a1 MO1

Article Images: [+] show captions
References [+] :
Akkers, A hierarchy of H3K4me3 and H3K27me3 acquisition in spatial gene regulation in Xenopus embryos. 2009, Pubmed, Xenbase