Which includes defects in pigmentation, and abnormal craniofacial and heart development. Several neurocristopathies have been documented, including frontonasal dysplasia, Waardenburg-Shah syndrome, DiGeorge syndrome, CHARGE syndrome, congenital nevi, and Hirchsprung disease. Induction, specification, migration, and differentiation of the NC cells are tightly regulated by a carefully orchestrated multi-step gene regulatory network. VE-821 neural crest formation occurs in a series of tightly regulated steps. First, the presumptive neural crest territory is induced at the dorsal neural plate border through the interplay of different signaling pathways including BMPs, Wnts and FGFs. These signals control the broad expression of a set of transcription factors at the neural plate border region, including Pax3, Msx1 and Zic1. These neural plate border specifiers further turn on the expression of a group of genes in the emerging neural crest cells, including Snail1, Snail2, FoxD3, Sox10, Sox9, and Twist1. These neural crest genes are extensively cross-regulated and many of them have been shown to be necessary and/or sufficient for the expression of many other genes. The neural crest specifier genes further control the expression of several downstream mediators of neural crest migration. Terminal differentiation of the neural crest cells is regulated by different networks. Folate deficiency has long been known to contribute to developmental neural defects, especially neural tube defects and neurocristopathies. In humans, it has been documentated folic acid prevents the development of neural tube defects, craniofacial malformation, and heart defects. In addition, in vivo and in vitro experiments suggest that altering levels of folic acid leads to aberrant cardiac NC cell migration and differentiation in chick. Folate is a cofactor in one-carbon metabolism and is a crucial regulator of nucleotide synthesis and methylation reactions. 5-methyltetrahydrofolate is involved in the remethylation of homocysteine to methionine, which is the precursor of S-adenosylmethionine, the primary methyl group donor for most biological methylation reactions. In humans, folate metabolism and folate status has been shown to affect the global methylation of DNA. As a water-soluble B class vitamin, the uptake of folate by cells is mediated by specific carriers or receptors, including folic acid receptors, proton-coupled folic acid transporter, and reduced folic acid carrier. RFC, a 12 transmembrane protein, is believed to be the major transporter for 5-MTHF, which is the major form of folate in circulation. RFC has a low affinity for folic acid and a high affinity for reduced folate and methotrexate, an antifolic acid chemotherapeutic drug. RFC is widely expressed in various human tissues and mouse embryos. RFC1 knockout mice die shortly after implantation. Supplementation of high dose of maternal folate prolongs the survival of RFC1 null embryos until mid-gestation, but these embryos develop multiple malformations, including defects in the neural tube, craniofacial and cardiac malformations. Such malformations, including the craniofacial and heart defects, coincide with neurocristopathies, suggesting that RFC might be required for normal neural crest development. Here we show in Xenopus embryos that RFC was involved.