Genetic, epigenetic, and environmental contributions to neural tube closure

Annual Review of Genetics

Volumn 48, Issue , 2014, Pages 583-611

  Wilde, Jonathan J ^a,b   Petersen, Juliette R ^a,b   Niswander, Lee ^a  

^a University of Colorado Denver and Children s Hospital Colorado   (United States)

^b UNIVERSITY OF COLORADO   (United States)

Author keywords

embryonic brain; embryonic spinal cord; epigenetics; gene environment interactions; neural tube defects

Indexed keywords

BRG1 PROTEIN; DNA METHYLTRANSFERASE 3A; DNA METHYLTRANSFERASE 3B; E1A ASSOCIATED P300 PROTEIN; FOLIC ACID; HISTONE ACETYLTRANSFERASE GCN5; HISTONE DEACETYLASE; HISTONE DEACETYLASE 4; MICRORNA 9; SIRTUIN 1; SONIC HEDGEHOG PROTEIN;

ALCOHOL CONSUMPTION; ANENCEPHALUS; ARTICLE; BIRTH DEFECT; CELL DIFFERENTIATION; CELL POLARITY; CELL PROLIFERATION; CPG ISLAND; DNA METHYLATION; DRUG USE; EMBRYO; EMBRYO DEVELOPMENT; EPIGENETICS; EUKARYOTIC FLAGELLUM; FOLIC ACID DEFICIENCY; GENE INTERACTION; GENE MUTATION; GENE REGULATORY NETWORK; GENETIC DISORDER; GENETIC REGULATION; GENETIC VARIABILITY; GENOTYPE ENVIRONMENT INTERACTION; HISTONE ACETYLATION; HISTONE MODIFICATION; HUMAN; HYPERTHERMIA; MATERNAL DIABETES MELLITUS; MATERNAL OBESITY; NEURAL TUBE; NEURAL TUBE DEFECT; NEUROECTODERM; NEUROEPITHELIUM; NEURULATION; NONHUMAN; NUCLEOSOME; PRENATAL EXPOSURE; SIGNAL TRANSDUCTION; SPINAL CORD; SPINAL DYSRAPHISM; TRANSCRIPTION INITIATION; ANIMAL; BRAIN; EMBRYOLOGY; FEMALE; GENETIC EPIGENESIS; GROWTH, DEVELOPMENT AND AGING; NEURAL CREST;

ANIMALS; BRAIN; EPIGENESIS, GENETIC; FEMALE; NEURAL CREST; NEURAL PLATE; NEURAL TUBE; SPINAL CORD;

EID: 84913593542     PISSN: 00664197     EISSN: 15452948     Source Type: Book Series    
DOI: 10.1146/annurev-genet-120213-092208     Document Type: Article

References (192)

1. Acs N, Bánhidy F, Puhó E, Czeizel AE. 2005. Maternal influenza during pregnancy and risk of congenital abnormalities in offspring. Birth Defects Res. A Clin. Mol. Teratol. 73(12):989-96
2. Aguilar A, Meunier A, Strehl L, Martinovic J, Bonniere M, et al. 2012. Analysis of human samples reveals impaired SHH-dependent cerebellar development in Joubert syndrome/Meckel syndrome. Proc. Natl. Acad. Sci. USA. 109:16951-56
3. Alvarez IS, Schoenwolf GC. 1992. Expansion of surface epithelium provides the major extrinsic force for bending of the neural plate. J. Exp. Zool. 261:340-48
4. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. 1999. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein. Nat. Genet. 23(2):185-88
5. Aran D, Sabato S, Hellman A. 2013. DNA methylation of distal regulatory sites characterizes dysregulation of cancer genes. Genome Biol. 14(3):R21
6. Artama M, Auvinen A, Raudaskoski T, Isojärvi I, Isojärvi J. 2005. Antiepileptic drug use of women with epilepsy and congenital malformations in offspring. Neurology 64:1874-78
7. Attia M, Murko C, Forster A, Lagger S, Rachez C, et al. 2011. Interaction between nucleosome assembly protein 1-like family members. J. Mol. Biol. 407(5):647-60
8. Attia M, Rachez C, De Pauw A, Avner P, Rogner UC. 2007. Nap1l2 promotes histone acetylation activity during neuronal differentiation. Mol. Cell. Biol. 27(17):6093-102
9. Bannister AJ, Kouzarides T. 2011. Regulation of chromatin by histonemodifications. Cell Res. 21(3):381-95
10. Banting GS. 2004. CECR2, a protein involved in neurulation, forms a novel chromatin remodeling complex with SNF2 L. Hum. Mol. Genet. 14(4):513-24
11. Barua S, Kuizon S, Chadman KK, Flory MJ, Brown WT, Junaid MA. 2014. Single-base resolution of mouse offspring brain methylome reveals epigenome modifications caused by gestational folic acid. Epigenet. Chromatin 7(1):1-15
12. Beaudin AE, Abarinov EV, Malysheva O, Perry CA, Caudill M, Stover PJ. 2011. Dietary folate, but not choline, modifies neural tube defect risk in Shmt1 knockout mice. Am. J. Clin. Nutr. 95:109-14
13. Beaudin AE, Abarinov EV, Noden DM, Perry CA, Chu S, et al. 2011. Shmt1 and de novo thymidylate biosynthesis underlie folate-responsive neural tube defects in mice. Am. J. Clin. Nutr. 93(4):789-98
14. Beaudin AE, Stover PJ. 2007. Folate-mediated one-carbon metabolism and neural tube defects: balancing genome synthesis and gene expression. Birth Defects Res. C Embryo Today 81(3):183-203
15. Benedum C, Yazdy M, Mitchell A, Werler M. 2013. Risk of spina bifida and maternal cigarette, alcohol, and coffee use during the first month of pregnancy. Int. J. Environ. Res. Public Health 10(8):3263-81
16. Bergman Y, Cedar H. 2013. DNA methylation dynamics in health and disease. Nat. Struct. Mol. Biol. 20(3):274-81
17. Blattler A, Ronan JL, Farnham PJ, Wu W, Crabtree GR. 2013. Cross-talk between site-specific transcription factors and DNA methylation states. J. Biol. Chem. 288(48):34287-94
18. Blom HJ, Shaw GM, den Heijer M, Finnell RH. 2006. Neural tube defects and folate: case far from closed. Nat. Rev. Neurosci. 7(9):724-31
19. Borgel J, Guibert S, Li Y, Chiba H, Schubeler D, et al. 2010. Targets and dynamics of promoter DNA methylation during early mouse development. Nat. Genet. 42(12):1093-100
20. Botto LD, Erickson JD, Mulinare J, Lynberg MC, Liu Y. 2002. Maternal fever, multivitamin use, and selected birth defects: evidence of interaction? Epidemiology 13(4):485-88
21. Boulet SL, Yang Q, Mai C, Kirby RS, Collins JS, et al. 2008. Trends in the postfortification prevalence of spina bifida and anencephaly in the United States. Birth Defects Res. A Clin. Mol. Teratol. 82(7):527-32
22. Bu P, Evrard YA, Lozano G, Dent SYR. 2007. Loss of Gcn5 acetyltransferase activity leads to neural tube closure defects and exencephaly in mouse embryos. Mol. Cell. Biol. 27(9):3405-16
23. Bultman SJ, Herschkowitz JI, Godfrey V, Gebuhr TC, Yaniv M, et al. 2007. Characterization of mammary tumors from Brg1 heterozygous mice. Oncogene 27(4):460-68
24. Cao Y, Zhao Z, Eckert RL, Reece EA. 2011. Protein kinase Cβ2 inhibition reduces hyperglycemiainduced neural tube defects through suppression of a caspase 8-triggered apoptotic pathway. Am. J. Obstet. 204:226; e1-5
25. Cao Y, Zhao Z, Eckert RL, Reece EA. 2012. The essential role of protein kinase Cδin diabetes-induced neural tube defects. J. Matern. Fetal Neonatal Med. 25(10):2020-24
26. Cassidy SB, Schwartz S. 1998. Prader-Willi and Angelman syndromes: disorders of genomic imprinting. Medicine 77(2):140-51
27. Caton PW, Nayuni NK, Kieswich J, Khan NQ, Yaqoob MM, Corder R. 2010. Metformin suppresses hepatic gluconeogenesis through induction of SIRT1 and GCN5. J. Endocrinol. 205(1):97-106
28. Cent. Dis. Control Prev. 2011. CDC Birth Defects Data/Statistics Registry. Atlanta, GA: Cent. Dis. Control Prev.
29. Cent. Dis. Control Prev. 1992. Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR Recomm. Rec. 41:1-77
30. Cent. Dis. Control Prev. 1998. Use of folic acid-containing supplements among women of childbearing age: United States, 1997. MMWR Morb. Mortal. Wkly. Rep. 47(7):131-34
31. Cervoni N. 2001. Demethylase activity is directed by histone acetylation. J. Biol. Chem. 276(44):40778-87
32. Chambers CD. 2006. Risks of hyperthermia associated with hot tub or spa use by pregnant women. Birth Defects Res. A Clin. Mol. Teratol. 76(8):569-73
33. Chen J, Lai F, Niswander L. 2012. The ubiquitin ligase mLin41 temporally promotes neural progenitor cell maintenance through FGF signaling. Genes Dev. 26(8):803-15
34. Chen X, Shen Y, Gao Y, Zhao H, Sheng X, et al. 2013. Detection of copy number variants reveals association of cilia genes with neural tube defects. PLoS ONE 8:e54492
35. Cheng H-L, Mostoslavsky R, Saito S, Manis JP, Gu Y, et al. 2003. Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice. Proc. Natl. Acad. Sci. USA. 100(19):10794-99
36. Copp AJ, Greene NDE. 2010. Genetics and development of neural tube defects. J. Pathol. 220(2):217-30
37. Correa A, Gilboa SM, Botto LD, Moore CA, Hobbs CA, et al. 2012. Lack of periconceptional vitamins or supplements that contain folic acid and diabetes mellitus-Associated birth defects. Am. J. Obstet. Gynecol. 206(3):218e1-13
38. Czeizel AE, Dudás I. 1992. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N. Engl. J. Med. 327(26):1832-35
39. Davidson CM, Northrup H, King TM, Fletcher JM, Townsend I, et al. 2008. Genes in glucose metabolism and association with spina bifida. Reprod. Sci. 15(1):51-58
40. Deak KL, Siegel DG, George TM, Gregory S, Ashley-Koch A, et al. 2008. Further evidence for a maternal genetic effect and a sex-influenced effect contributing to risk for human neural tube defects. Birth Defects Res. A Clin. Mol. Teratol. 82(10):662-69
41. De Marco P, Merello E, Calevo MG, Mascelli S, Pastorino D, et al. 2011. Maternal periconceptional factors affect the risk of spina bifida-Affected pregnancies: an Italian case-control study. Child's Nerv. Syst. 27(7):1073-81
42. De Wals P, Tairou F, Van Allen MI, Uh S-H, Lowry RB, et al. 2007. Reduction in neural-tube defects after folic acid fortification in Canada. N. Engl. J. Med. 357(2):135-42
43. Dreier JW, Andersen AMN, Berg-Beckhoff G. 2014. Systematic review and meta-Analyses: fever in pregnancy and health impacts in the offspring. Pediatrics 133(3):e674-88
44. Duong HT, Shahrukh Hashmi S, Ramadhani T, Canfield MA, Scheuerle A, et al. 2011. Maternal use of hot tub and major structural birth defects. Birth Defects Res. A Clin. Mol. Teratol. 91(9):836-41
45. Edwards MJ, Saunders RD, Shiota K. 2003. Effects of heat on embryos and foetuses. Int. J. Hyperthermia 19(3):295-324
46. FDA. 1996. Food Standards: Amendment of Standards of Identity for Enriched Grain Products to Require Addition of Folic Acid, Washington, DC: FDA.
47. Feil R, Waterland RA, Fraga MF, Jirtle RL. 2012. Epigenetics and the environment: emerging patterns and implications. Nat. Rev. Genet. 13(2):97-109
48. Feldkamp ML, Meyer RE, Krikov S, Botto LD. 2010. Acetaminophen use in pregnancy and risk of birth defects. Obstet. Gynecol. 115(1):109-15
49. Finnell RH, Moon SP, Abbott LC, Golden JA, Chernoff GF. 1986. Strain differences in heat-induced neural tube defects in mice. Teratology 33(2):247-52
50. Foster WH, Langenbacher A, Gao C, Chen J, Wang Y. 2013. Nuclear phosphatase PPM1G in cellular survival and neural development. Dev. Dyn. 242(9):1101-9
51. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, et al. 1995. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat. Genet. 10(1):111-13
52. Fukuda T, Li E, Tokunaga A, Bestor TH, Sakamoto R, et al. 2011. Fbxl10/Kdm2b deficiency accelerates neural progenitor cell death and leads to exencephaly. Mol. Cell. Neurosci. 46(3):614-24
53. Gao Q, Gao Y-M. 2007. Hyperglycemic condition disturbs the proliferation and cell death of neural progenitors in mouse embryonic spinal cord. Int. J. Dev. Neurosci. 25(6):349-57
54. Gäreskog M, Eriksson UJ, Wentzel P. 2006. Combined supplementation of folic acid and vitamin E diminishes diabetes-induced embryotoxicity in rats. Birth Defects Res. A Clin. Mol. Teratol. 76(6):483-90
55. Gelineau-vanWaes J, Starr L, Maddox J, Aleman F, Voss KA, et al. 2005. Maternal fumonisin exposure and risk for neural tube defects: mechanisms in an in vivo mouse model. Birth Defects Res. A Clin. Mol. Teratol. 73(7):487-97
56. George L, Granath F, Johansson ALV, Annerén G, Cnattingius S. 2006. Environmental tobacco smoke and risk of spontaneous abortion. Epidemiology 17(5):500-5
57. Goetzinger KR, Stamilio DM, Dicke JM, Macones GA, Odibo AO. 2008. Evaluating the incidence and likelihood ratios for chromosomal abnormalities in fetuses with common central nervous system malformations. Am. J. Obstet. Gynecol. 199(3):285e1-6
58. Graham JM, Ferm VH. 1985. Heat-And alcohol-induced neural tube defects: interactions with folate in a golden hamster model. Pediatr. Res. 19(2):247-51
59. Gray JD, Nakouzi G, Slowinska-Castaldo B, Dazard J-E, Rao JS, et al. 2010. Functional interactions between the LRP6WNT co-receptor and folate supplementation. Hum. Mol. Genet. 19(23):4560-72
60. Greenberg JA, Bell SJ, Guan Y, Yu Y-H. 2011. Folic acid supplementation and pregnancy: more than just neural tube defect prevention. Rev. Obstet. Gynecol. 4(2):52-59
61. Greene NDE, Stanier P, Copp AJ. 2009. Genetics of human neural tube defects. Hum. Mol. Genet. 18(R2):R113-29
62. Greene NDE, Stanier P, Moore GE. 2011. The emerging role of epigenetic mechanisms in the etiology of neural tube defects. Epigenetics 6(7):875-83
63. Haas J, Frese KS, Park YJ, Keller A, Vogel B, et al. 2013. Alterations in cardiac DNA methylation in human dilated cardiomyopathy. EMBO Mol. Med. 5(3):413-29
64. Haghighi Poodeh S, Alhonen L, Salonurmi T, Savolainen MJ. 2014. Ethanol-induced impairment of polyamine homeostasis: a potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome. Biochem. Biophys. Res. Commun. 446:173-78
65. Hall J, Solehdin F. 1998. Folic acid for the prevention of congenital anomalies. Eur. J. Pediatr. 157(6):445-50
66. Hargreaves DC, Crabtree GR. 2011. ATP-dependent chromatin remodeling: genetics, genomics and mechanisms. Cell Res. 21:396-420
67. Harmacek L, Watkins-Chow DE, Chen J, Jones KL, Pavan WJ, et al. 2014. A unique missense allele of BAF155, a core BAF chromatin remodeling complex protein, causes neural tube closure defects in mice. Dev. Neurobiol. 74:483-97
68. Harris MJ. 2009. Insights into prevention of human neural tube defects by folic acid arising from consideration of mouse mutants. Birth Defects Res. A Clin. Mol. Teratol. 85(4):331-39
69. Harris MJ, Juriloff DM. 2007. Mouse mutants with neural tube closure defects and their role in understanding human neural tube defects. Birth Defects Res. A Clin. Mol. Teratol. 79(3):187-210
70. Harris MJ, Juriloff DM. 2010. An update to the list of mouse mutants with neural tube closure defects and advances toward a complete genetic perspective of neural tube closure. Birth Defects Res. A Clin. Mol. Teratol. 88(8):653-69
71. Hata K, Okano M, Lei H, Li E. 2002. Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice. Development 129(8):1983-93
72. He L, Cao J, Meng S, Ma A, Radovick S, Wondisford FE. 2013. Activation of basal gluconeogenesis by coactivator p300 maintains hepatic glycogen storage. Mol. Endocrinol. 27(8):1322-32
73. Heintzman ND, Ren B. 2009. Finding distal regulatory elements in the human genome. Curr. Opin. Genet. Dev. 19(6):541-49
74. Hendricks KA, Nuno OM, Suarez L, Larsen R. 2001. Effects of hyperinsulinemia and obesity on risk of neural tube defects among Mexican Americans. Epidemiology 12(6):630-35
75. Hibbard ED, Smithells RW. 1965. Folic acid metabolism and human embryopathy. Lancet 285(7398):1254
76. Hirabayashi Y, Schaniel C, Pujadas E, Banting GS, Gotoh Y, et al. 2010. Epigenetic control of neural precursor cell fate during development. Nat. Rev. Neurosci. 11:377-88
77. Hiramatsu Y, Sekiguchi N, Hayashi M, Isshiki K, Yokota T, et al. 2002. Diacylglycerol production and protein kinaseCactivity are increased in a mousemodel of diabetic embryopathy. Diabetes 51(9):2804-10
78. Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-André V, et al. 2013. Super-enhancers in the control of cell identity and disease. Cell 155(4):934-47
79. Hook EB, Czeizel AE. 1997. Can terathanasia explain the protective effect of folic-Acid supplementation on birth defects? Lancet 350(9076):513-15
80. Hoyo C, Murtha AP, Schildkraut JM, Forman MR, Calingaert B, et al. 2011. Folic acid supplementation before and during pregnancy in the Newborn Epigenetics STudy (NEST). BMC Public Health 11(1):46
81. Jo ó JG, Beke A, Papp C, Toth-Pál E, Csaba A, et al. 2007. Neural tube defects in the sample of genetic counselling. Prenat. Diagn. 27(10):912-21
82. Juriloff DM, Harris MJ. 2012. A consideration of the evidence that genetic defects in planar cell polarity contribute to the etiology of human neural tube defects. BirthDefects Res. A Clin. Mol. Teratol. 94(10):824-40
83. Kappen C, Salbaum JM. 2014. Gene expression in teratogenic exposures: a new approach to understanding individual risk. Reprod. Toxicol. 45:94-104
84. Kibar Z, Torban E, McDearmid JR, Reynolds A, Berghout J, et al. 2007. Mutations in VANGL1 associated with neural-tube defects. N. Engl. J. Med. 356(14):1432-37
85. Kim JK, Huh SO, Choi H, Lee KS, Shin D, et al. 2001. Srg3, a mouse homolog of yeast SWI3, is essential for early embryogenesis and involved in brain development. Mol. Cell Biol. 21(22):7787-95
86. Korstanje R, Desai J, Lazar G, King B, Rollins J, et al. 2008. Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects. Physiol. Genomics 35(3):296-304
87. Kost K. 2013. Unintended Pregnancy Rates at the State Level: Estimates For 2002, 2004, 2006 and 2008. New York: Guttmacher Instit.
88. Kouzarides T. 2007. Chromatin modifications and their function. Cell 128(4):693-705
89. Krebs AR, Karmodiya K, Lindahl-Allen M, Struhl K, Tora L. 2011. SAGA and ATAC histone acetyl transferase complexes regulate distinct sets of genes and ATAC defines a class of p300-independent enhancers. Mol. Cell 44(3):410-23
90. Kruman II, Fowler A-K. 2014. Impaired one carbon metabolism and DNA methylation in alcohol toxicity. J. Neurochem. 192:770-80
91. Kyttala M, Tallila J, Salonen R, Kopra O, Kohlschmidt N, et al. 2006. MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome. Nat. Genet. 38:155-57
92. Lacasana M, Blanco-Munoz J, Borja-Aburto VH, Aguilar-Garduno C, Rodŕ?guez-Barranco M, et al. 2012. Effect on risk of anencephaly of gene-nutrient interactions between methylenetetrahydrofolate reductase C677T polymorphism and maternal folate, vitamin B12 and homocysteine profile. Public Health Nutr. 15(8):1419-28
93. Lakkis MM, Golden JA, O'Shea KS, Epstein JA. 1999. Neurofibromin deficiency in mice causes exencephaly and is a modifier for Splotch neural tube defects. Dev. Biol. 212(1):80-92
94. Lee JE, Gleeson JG. 2011. Cilia in the nervous system: linking cilia function and neurodevelopmental disorders. Curr. Opin. Neurol. 24:98-105
95. Lemos MC, Harding B, Reed AAC, Jeyabalan J, Walls GV, et al. 2009. Genetic background influences embryonic lethality and the occurrence of neural tube defects in Men1 null mice: relevance to genetic modifiers. J. Endocrinol. 203(1):133-42
96. Lerin C, Rodgers JT, Kalume DE, Kim S-H, Pandey A, Puigserver P. 2006. GCN5 acetyltransferase complex controls glucose metabolism through transcriptional repression of PGC-1α. Cell Metab. 3(6):429-38
97. Li CCY, Cropley JE, Cowley MJ, Preiss T, Martin DIK, Suter CM. 2011. A sustained dietary change increases epigenetic variation in isogenic mice. PLOS Genet. 7(4):e1001380
98. Li E, Bestor TH, Jaenisch R. 1992. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69(6):915-26
99. Li X, Weng H, Reece EA, Yang P. 2011. SOD1 overexpression in vivo blocks hyperglycemia-induced specific PKC isoforms: substrate activation and consequent lipid peroxidation in diabetic embryopathy. Am. J. Obstet. Gynecol. 205(1):84e1-6
100. Li X, Weng H, Xu C, Reece EA, Yang P. 2012. Oxidative stress-induced JNK1/2 activation triggers proapoptotic signaling and apoptosis that leads to diabetic embryopathy. Diabetes 61(8):2084-92
101. Li X, Xu C, Yang P. 2013. C-Jun NH2-terminal kinase 1/2 and endoplasmic reticulum stress as interdependent and reciprocal causation in diabetic embryopathy. Diabetes 62(2):599-608
102. Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC. 2005. Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J. Nutr. 135(6):1382-86
103. Logan CV, Abdel-Hamed Z, Johnson CA. 2011. Molecular genetics and pathogenic mechanisms for the severe ciliopathies: insights into neurodevelopment and pathogenesis of neural tube defects. Mol. Neurobiol. 43:12-26
104. Ĺ opez-Camelo JS, Orioli IM, da Gracą Dutra M, Nazer-Herrera J, Rivera N, et al. 2005. Reduction of birth prevalence rates of neural tube defects after folic acid fortification in Chile. Am. J. Med. Genet. A 135(2):120-25
105. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, et al. 2012. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380(9859):2095-128
106. Lundberg YW, Wing MJ, Xiong W, Zhao J, Finnell RH. 2003. Genetic dissection of hyperthermiainduced neural tube defects in mice. Birth Defects Res. A Clin. Mol. Teratol. 67(6):409-13
107. Lupo PJ, Canfield MA, Chapa C, Lu W, Agopian AJ, et al. 2012. Diabetes and obesity-related genes and the risk of neural tube defects in the national birth defects prevention study. Am. J. Epidemiol. 176(12):1101-9
108. Lupo PJ, Mitchell LE, Canfield MA, Shaw GM, Olshan AF, et al. 2014. Maternal-fetal metabolic genegene interactions and risk of neural tube defects. Mol. Genet. Metab. 111(1):46-51
109. Makelarski JA, Romitti PA, Sun L, Burns TL, Druschel CM, et al. 2013. Periconceptional maternal alcohol consumption and neural tube defects. Birth Defects Res. A Clin. Mol. Teratol. 97(3):152-60
110. Marean A, Graf A, Zhang Y, Niswander L. 2011. Folic acid supplementation can adversely affect murine neural tube closure and embryonic survival. Hum. Mol. Genet. 20(18):3678-83
111. Massarwa R, Niswander L. 2013. In toto live imaging of mouse morphogenesis and new insights into neural tube closure. Development 140(1):226-36
112. Matok I, Gorodischer R, Koren G, Landau D, Wiznitzer A, Levy A. 2009. Exposure to folic acid antagonists during the first trimester of pregnancy and the risk of major malformations. Br. J. Clin. Pharmacol. 68(6):956-62
113. Michie CA. 1991. Neural tube defects in 18th century. Lancet 337:504
114. Milunsky A, Ulcickas M, Rothman KJ, Willett W, Jick SS, Jick H. 1992. Maternal heat exposure and neural tube defects. J. Am. Med. Assoc. 268(7):882-85
115. Miranda TB, Bassuk AG, Jones PA, Kibar Z. 2007. DNA methylation: the nuts and bolts of repression. J. Cell. Physiol. 213(2):384-90
116. Momb J, Lewandowski JP, Bryant JD, Fitch R, Surman DR, et al. 2013. Deletion of Mthfd1l causes embryonic lethality and neural tube and craniofacial defects inmice. Proc. Natl. Acad. Sci. USA110(2):549-54
117. MRC Vitam. Study Res. Group. 1991. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 338(8760):131-37
118. Murko C, Lagger S, Steiner M, Seiser C, Schoefer C, Pusch O. 2013. Histone deacetylase inhibitor trichostatin A induces neural tube defects and promotes neural crest specification in the chicken neural tube. Differentiation 85(1-2):55-66
119. Nagy Z, Riss A, Romier C, le Guezennec X, Dongre AR, et al. 2009. The human SPT20-containing SAGA complex plays a direct role in the regulation of endoplasmic reticulum stress-induced genes. Mol. Cell. Biol. 29(6):1649-60
120. Narisawa A, Komatsuzaki S, Kikuchi A, Niihori T, Aoki Y, et al. 2012. Mutations in genes encoding the glycine cleavage system predispose to neural tube defects in mice and humans. Hum. Mol. Genet. 21(7):1496-503
121. Nishimura T, Takeichi M. 2008. Shroom3-mediated recruitment of Rho kinases to the apical cell junctions regulates epithelial and neuroepithelial planar remodeling. Development 135:1493-502
122. Obican SG, Finnell RH, Mills JL, Shaw GM, Scialli AR. 2010. Folic acid in early pregnancy: a public health success story. FASEB J. 24(11):4167-74
123. Okano M, Bell DW, Haber DA, Li E. 1999. DNA methyl transferases Dnmt 3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99(3):247-57
124. Omori H, Otsu M, Suzuki A, Nakayama T, Akama K, et al. 2014. Effects of heat shock on survival, proliferation and differentiation of mouse neural stem cells. Neurosci. Res. 79:13-21
125. Ortega RM, Requejo AM, Ĺ opez-Sobaler AM, Navia B, Mena MC, et al. 2004. Smoking and passive smoking as conditioners of folate status in young women. J. Am. Coll. Nutr. 23(4):365-71
126. Ougland R, Lando D, Jonson I, Dahl JA, Moen MN, et al. 2012. ALKBH1 is a histone H2A dioxygenase involved in neural differentiation. Stem Cells 30(12):2672-82
127. Parker SE, Yazdy MM, Tinker SC, Mitchell AA, Werler MM. 2013. The impact of folic acid intake on the association among diabetes mellitus, obesity, and spina bifida. Am. J. Obstet. Gynecol. 209(3):239e1-8
128. Partanen M, Motoyama J, Hui CC. 1999. Developmentally regulated expression of the transcriptional cofactors/histone acetyltransferasesCBPand p300 duringmouse embryogenesis. Int. J. Dev. Biol. 43:487-94
129. Pfeiffer CM, Hughes JP, Lacher DA, Bailey RL, Berry RJ, et al. 2012. Estimation of trends in serum and RBC folate in the U. S. population from pre-to postfortification using assay-Adjusted data from the NHANES 1988-2010. J. Nutr. 142(5):886-93
130. Pujadas E, Feinberg AP. 2012. Regulated noise in the epigenetic landscape of development and disease. Cell 148(6):1123-31
131. Raj A, Rifkin SA, Andersen E, van Oudenaarden A. 2011. Variability in gene expression underlies incomplete penetrance. Nature 463(7283):913-18
132. Rasmussen SA, Chu SY, Kim SY, Schmid CH, Lau J. 2008. Maternal obesity and risk of neural tube defects: a metaanalysis. Am. J. Obstet. Gynecol. 198(6):611-19
133. Ray HJ, Niswander L. 2012. Mechanisms of tissue fusion during development. Development 139(10):1701-11
134. Ray JG, Wyatt PR, Vermeulen MJ, Meier C, Cole DEC. 2005. Greatermaternal weight and the ongoing risk of neural tube defects after folic acid flour fortification. Obstet. Gynecol. 105(2):261-65
135. Reece EA. 2012. Diabetes-induced birth defects:What do we know? What can we do? Curr. Diab. Rep. 12(1):24-32
136. Robert E, Smith-Roe SL, Guibaud P, Bultman SJ. 1982. Maternal valproic acid and congenital neural tube defects. Lancet 320(8304):937
137. Robinson A, Escuin S, Doudney K, Vekemans M, Stevenson RE, et al. 2012. Mutations in the planar cell polarity genes CELSR1 and SCRIB are associated with the severe neural tube defect craniorachischisis. Hum. Mutat. 33(2):440-47
138. Rogner UC, Spyropoulos DD, Le Novère N, Changeux JP, Avner P. 2000. Control of neurulation by the nucleosome assembly protein-1-like. Nat. Genet. 25(4):431-35
139. Sadler TW, Merrill AH, Stevens VL, Sullards MC, Wang E, Wang P. 2002. Prevention of fumonisin B1-induced neural tube defects by folic acid. Teratology 66(4):169-76
140. Sakai M, Tujimura T, Yongheng C, Noguchi T, Inagaki K, et al. 2012. CITED2 links hormonal signaling to PGC-1α; acetylation in the regulation of gluconeogenesis. Nat. Med. 18:612-17
141. Salbaum JM, Kappen C. 2010. Neural tube defect genes and maternal diabetes during pregnancy. Birth Defects Res. A Clin. Mol. Teratol. 88(8):601-11
142. Sandford MK, Kissling GE, Joubert PE. 1992. Neural tube defect etiology: new evidence concerning maternal hyperthermia, health and diet. Dev. Med. Child Neurol. 34(8):661-75
143. Sandovici I, Harris MJ, Smith NH, Juriloff DM, Nitert MD, et al. 2011. Maternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets. Proc. Natl. Acad. Sci. USA 108(13):5449-54
144. Sanyal A, Lajoie BR, Jain G, Dekker J. 2012. The long-range interaction landscape of gene promoters. Nature 489(7414):109-13
145. Saxén L, Holmberg PC, Nurminen M, Kuosma E. 1982. Sauna and congenital defects. Teratology 25(3):309-13
146. Schaniel C, Ang Y-S, Ratnakumar K, Cormier C, James T, et al. 2009. Smarcc1/Baf155 couples selfrenewal gene repression with changes in chromatin structure in mouse embryonic stem cells. Stem Cells 27:2979-91
147. Schmidt RJ, Romitti PA, Burns TL, Browne ML, Druschel CM, et al. 2009. Maternal caffeine consumption and risk of neural tube defects. Birth Defects Res. A Clin. Mol. Teratol. 85(11):879-89
148. Schwartz YB, Pirrotta V. 2007. Polycomb silencing mechanisms and the management of genomic programmes. Nat. Rev. Genet. 8(1):9-22
149. Shakèd M, Weissmuller K, Svoboda H, Hortschansky P, Nishino N, et al. 2008. Histone deacetylases control neurogenesis in embryonic brain by inhibition of BMP2/4 signaling. PLOS ONE 3(7):e2668
150. Shaw GM, Todoroff K, Finnell RH, Lammer EJ. 2000. Spina bifida phenotypes in infants or fetuses of obese mothers. Teratology 61(5):376-81
151. Shin J-H, Shiota K. 1999. Folic acid supplementation of pregnant mice suppresses heat-induced neural tube defects in the offspring. J. Nutr. 129:2070-73
152. Shpargel KB, Sengoku T, Yokoyama S, Magnuson T. 2012. UTX and UTY demonstrate histone demethylase-independent function in mouse embryonic development. PLoS Genet. 8(9):e1002964
153. Shyamasundar S, Jadhav SP, Bay BH, Tay SSW, Kumar SD, et al. 2013. Analysis of epigenetic factors in mouse embryonic neural stem cells exposed to hyperglycemia. PLOS ONE 8(6):e65945
154. Steegers-Theunissen RP, Obermann-Borst SA, Kremer D, Lindemans J, Siebel C, et al. 2009. Periconceptional maternal folic acid use of 400 μg per day is related to increased methylation of the IGF2 gene in the very young child. PLOS ONE 4(11):e7845
155. Stothard KJ, Tennant PWG, Bell R, Rankin J. 2009. Maternal overweight and obesity and the risk of congenital anomalies: a systematic review and meta-Analysis. J. Am. Med. Assoc. 301(6):636-50
156. Stover PJ, Caudill MA. 2008. Genetic and epigenetic contributions to human nutrition and health: managing genome-diet interactions. J. Am. Diet. Assoc. 108(9):1480-87
157. Struhl K, Rogner UC, Segal E, Spyropoulos DD, Le Novère N, et al. 2013. Determinants of nucleosome positioning. Nat. Struct. Mol. Biol. 20(3):267-73
158. Suarez L, Felkner M, Brender JD, Canfield M, Hendricks K. 2007. Maternal exposures to cigarette smoke, alcohol, and street drugs and neural tube defect occurrence in offspring. Matern. Child Health J. 12(3):394-401
159. Suarez L, Felkner M, Brender JD, Canfield M, Zhu H, Hendricks KA. 2012. Neural tube defects on the Texas-Mexico border: what we've learned in the 20 years since the Brownsville cluster. Birth Defects Res. A Clin. Mol. Teratol. 94(11):882-92
160. Suarez L, Felkner M, Hendricks K. 2004. The effect of fever, febrile illnesses, and heat exposures on the risk of neural tube defects in a Texas-Mexico border population. Birth Defects Res. A Clin. Mol. Teratol. 70(10):815-19
161. Suzuki MM, Zhang Y, Salbaum JM, Bamforth SD, Bird A, et al. 2008. DNA methylation landscapes: provocative insights from epigenomics. Nat. Rev. Genet. 9(6):465-76
162. Takeuchi T, Yamazaki Y, Katoh-Fukui Y, Tsuchiya R, Kondo S, et al. 1995. Gene trap capture of a novel mouse gene, jumonji, required for neural tube formation. Genes Dev. 9(10):1211-22
163. Thiersch JB. 1952. Therapeutic abortions with a folic acid antagonist, 4-Aminopteroylglutamic acid (4-Amino P. G. A) administered by the oral route. Am. J. Obstet. Gynecol. 63(6):1298-304
164. Thiersch JB, Philips FS. 1950. Effect of 4-Amino-pteroylglutamic acid (aminopterin) on early pregnancy. Proc. Soc. Exp. Biol. Med. 74(1):204-8
165. van der Put NM, Steegers-Theunissen RP, Frosst P, Trijbels FJ, Eskes TK, et al. 1995. Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet 346(8982):1070-71
166. Vega RB, Matsuda K, Oh J, Barbosa AC, Yang X, et al. 2004. Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell 119(4):555-66
167. Villanueva JA, Halsted CH. 2004. Hepatic transmethylation reactions in micropigs with alcoholic liver disease. Hepatology 39(5):1303-10
168. Wald NJ, Law MR, Morris JK, Wald DS. 2001. Quantifying the effect of folic acid. Lancet 358(9298):2069-73
169. Waller DK, Shaw GM, Rasmussen SA, Hobbs CA, Canfield MA, et al. 2007. Prepregnancy obesity as a risk factor for structural birth defects. Arch. Pediatr. Adolesc. Med. 161(8):745-50
170. Wallingford JB. 2012. Planar cell polarity and the developmental control of cell behavior in vertebrate embryos. Annu. Rev. Cell Dev. Biol. 28:627-53
171. Wallingford JB, Niswander LA, Shaw GM, Finnell RH. 2013. The continuing challenge of understanding, preventing, and treating neural tube defects. Science 339(6123):1222002
172. Wang F, Reece EA, Yang P. 2013. Superoxide dismutase 1 overexpression in mice abolishes maternal diabetes-induced endoplasmic reticulum stress in diabetic embryopathy. Am. J. Obstet. Gynecol. 209(4):345e1-7
173. Wang M, Wang Z-P, Gong R, Zhao Z-T. 2014. Maternal smoking during pregnancy and neural tube defects in offspring: a meta-Analysis. Child's Nerv. Syst. 30(1):83-89
174. Wang M, Wang Z-P, Zhang M, Zhao Z-T. 2014. Maternal passive smoking during pregnancy and neural tube defects in offspring: a meta-Analysis. Arch. Gynecol. Obstet. 289(3):513-21
175. Warkany J, Beaudry PH, Hornstein S. 1959. Attempted abortion with aminopterin (4-Aminopteroylglutamic acid); malformations of the child. Am. Med. Assoc. J. Dis. Child 97(3):274-81
176. Waterland RA, Jirtle RL. 2003. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol. Cell. Biol. 23(15):5293-300
177. Weatherbee SD, Niswander LA, Anderson KV. 2009. A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and hedgehog signaling. Hum. Mol. Genet. 18:4565-75
178. Wei X, Li H, Miao J, Liu B, Zhan Y, et al. 2013. MiR-9?-And miR-124a-mediated switching of chromatin remodelling complexes is altered in rat spina bifida aperta. Neurochem. Res. 38(8):1605-15
179. Welstead GG, Creyghton MP, Bilodeau S, Cheng AW, Markoulaki S, et al. 2012. X-linked H3K27me3 demethylase Utx is required for embryonic development in a sex-specific manner. Proc. Natl. Acad. Sci. USA 109(32):13004-9
180. Xu C, Li X, Wang F, Weng H, Yang P. 2013. Trehalose prevents neural tube defects by correctingmaternal diabetes-suppressed autophagy and neurogenesis. Am. J. Physiol. Endocrinol. Metab. 305(5):E667-78
181. Yan L, Zhao L, Long Y, Zou P, Ji G, et al. 2012. Association of the maternal MTHFR C677T polymorphism with susceptibility to neural tube defects in offsprings: evidence from 25 case-control studies. PLOS ONE 7(10):e41689
182. Yang P, Li X, Xu C, Eckert RL, Reece EA, et al. 2013. Maternal hyperglycemia activates an ASK1-FoxO3a-caspase 8 pathway that leads to embryonic neural tube defects. Sci. Signal. 6(290):ra74
183. Yang P, Zhao Z, Reece EA. 2007. Involvement of c-Jun N-terminal kinases activation in diabetic embryopathy. Biochem. Biophys. Res. Commun. 357(3):749-54
184. Yazdy MM, Tinker SC, Mitchell AA, Demmer LA, Werler MM. 2012. Maternal tea consumption during early pregnancy and the risk of spina bifida. Birth Defects Res. A Clin. Mol. Teratol. 94(10):756-61
185. Ybot-Gonzalez P, Savery D, Gerrelli D, Signore M, Mitchell CE, et al. 2007. Convergent extension, planar-cell-polarity signalling and initiation of mouse neural tube closure. Development 134(4):789-99
186. Ye R, Ren A, Zhang L, Li Z, Liu J, et al. 2011. Tea drinking as a risk factor for neural tube defects in northern China. Epidemiology 22(4):491-96
187. Yin Z, Haynie J, Yang X, Han B, Kiatchoosakun S, et al. 2002. The essential role of Cited2, a negative regulator forHIF-1α, in heart development and neurulation. Proc. Natl. Acad. Sci. USA 99(16):10488-93
188. Youngblood ME, Williamson R, Bell KN, Johnson Q, Kancherla V, Oakley GP Jr. 2013. 2012 Update on global prevention of folic acid-preventable spina bifida and anencephaly. Birth Defects Res. A Clin. Mol. Teratol. 97(10):658-63
189. Yuan Q, Zhao S, Liu S, Zhang Y, Fu J, et al. 2013. Folic acid supplementation changes the fate of neural progenitors in mouse embryos of hyperglycemic and diabetic pregnancy. J. Nutr. Biochem. 24(7):1202-12
190. Zabihi S, Loeken MR. 2010. Understanding diabetic teratogenesis: Where are we now and where are we going? Birth Defects Res. A Clin. Mol. Teratol. 88(10):779-90
191. Zhang T, Lou J, Zhong R, Wu J, Zou L, et al. 2013. Genetic variants in the folate pathway and the risk of neural tube defects: a meta-Analysis of the published literature. PLOS ONE 8(4):e59570
192. Zhao Z, Yang P, Eckert RL, Reece EA. 2009. Caspase-8: a key role in the pathogenesis of diabetic embryopathy. Birth Defects Res. B Dev. Reprod. Toxicol. 86(1):72-77