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XB-ART-54132
FASEB J January 1, 2017; 31 (8): 3622-3635.

Folate-dependent methylation of septins governs ciliogenesis during neural tube closure.

Toriyama M , Toriyama M , Wallingford JB , Finnell RH .


Abstract
Periconception maternal folic acid (vitamin B9) supplementation can reduce the prevalence of neural tube defects (NTDs), although just how folates benefit the developing embryo and promote closing of the neural tube and other morphologic processes during development remains unknown. Folate contributes to a 1-carbon metabolism, which is essential for purine biosynthesis and methionine recycling and affects methylation of DNA, histones, and nonhistone proteins. Herein, we used animal models and cultured mammalian cells to demonstrate that disruption of the methylation pathway mediated by folate compromises normal neural tube closure (NTC) and ciliogenesis. We demonstrate that the embryos with NTD failed to adequately methylate septin2, a key regulator of cilium structure and function. We report that methylation of septin2 affected its GTP binding activity and formation of the septin2-6-7 complex. We propose that folic acid promotes normal NTC in some embryos by regulating the methylation of septin2, which is critical for normal cilium formation during early embryonic development.-Toriyama, M., Toriyama, M., Wallingford, J. B., Finnell, R. H. Folate-dependent methylation of septins governs ciliogenesis during neural tube closure.

PubMed ID: 28432198
PMC ID: PMC5503710
Article link: FASEB J
Grant support: [+]

Species referenced: Xenopus
Genes referenced: arl13b fbrs gli3 prss1 rfc1 septin2 septin6 septin7 shh slc19a1 slc7a5 tcf3 ttr tub wnt1
GO keywords: neural tube closure [+]

Disease Ontology terms: neural tube defect
OMIMs: NEURAL TUBE DEFECTS, FOLATE-SENSITIVE; NTDFS

Article Images: [+] show captions
References [+] :
Bai, DNA methyltransferase 3b regulates nerve growth factor-induced differentiation of PC12 cells by recruiting histone deacetylase 2. 2005, Pubmed