Defective neural crest development leads to a broad spectrum of congenital malformations, collectively called neurocristopathies, which includes defects in pigmentation, and abnormal craniofacial and heart development. Folic acid has been shown to have protective effect against neurocristopathic malformations and has been used as a powerful medicine for pregnant women for more than 20 years. However, the underlying mechanism remains largely unknown. Folate, a member of the vitamin B family, functions in a series of vital biological processes, including the synthesis of DNA and amino acid, cell cycle control, and one carbon unit cycle which is important for DNA and protein methylation. As a water-soluble B class of vitamin, the uptake of folate by cells is mediated by specific carriers or receptors, including folic acid receptors (FRs) and reduced folic acid carrier (RFC).We showed here that in Xenopus RFC (XRFC) is specifically expressed in neural crest tissues. Knockdown of XRFC resulted in severe neurocristopathies, as well as loss of neural crest marker gene expressions. On the other hand, over-expression 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 results suggested that the RFC mediated folate metabolic pathway likely potentiates neural crest gene expression through epigenetic modifications and manifested the role of nutrients in gene transcriptional regulation through epigenetic modification. We also found that elongation protein 3 (Elp3) is involved in Xenopus neural crest development. Elp3 contains a SAM radical domain and a HAT (histone acetyltransferase) domain and has DNA demethylation and histone acetylization activities.We found that Xenopus Elp3 is highly expressed in migrating neural crest.Overexpression and knockdown of XElp3 affect neural crest induction and migration and both the SAM domain and the HAT domain are required for its activity.Immune-staining experiment indicates that Elp3 is required for proper H3/H4 acetylization in Xenopus embryos. Glioma is the most common primary brain tumor.We found that nicotinic acid (NA) specifically disrupted the intracellular calcium balance in glioma but not neuronal cells.In glioma cells,NA induced cell apoptosis through caspase dependent and independent pathways(ER stress). We also showed that in glioma cells, NA distributed the leading edge formation through the up-regulation of trpm7, which phosphorylates Myosin IIA causing disassembly of the leading edge. Further work in rat model indicated that NA was also able to inhibit glioma growth in vivo and might be a new candidate for clinical glioma therapy.
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