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Scientifica
Volume 2017, Article ID 5364827, 29 pages
https://doi.org/10.1155/2017/5364827
Review Article

Spina Bifida: Pathogenesis, Mechanisms, and Genes in Mice and Humans

1Department of Parasitology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
2Laboratory for Fetal and Regenerative Biology, Colorado Fetal Care Center, Division of Pediatric Surgery, Children’s Hospital Colorado, University of Colorado, Anschutz Medical Campus, 12700 E 17th Ave, Aurora, CO 80045, USA
3Training and Technical Division, Islamic Hospital, Abdali, Amman 2414, Jordan
4Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia

Correspondence should be addressed to Noraishah M. Abdul-Aziz; ym.ude.cmmu@ahsion

Received 20 June 2016; Revised 14 November 2016; Accepted 1 December 2016; Published 13 February 2017

Academic Editor: Heinz Hofler

Copyright © 2017 Siti W. Mohd-Zin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. M. Szymanski, R. Misseri, B. Whittam et al., “Quality of life assessment in spina bifida for children (QUALAS-C): development and validation of a novel health-related quality of life instrument,” Urology, vol. 87, pp. 178–184, 2016. View at Publisher · View at Google Scholar
  2. N. Fischer, P. Church, J. Lyons, and A. C. Mcpherson, “A qualitative exploration of the experiences of children with spina bifida and their parents around incontinence and social participation,” Child: Care, Health and Development, vol. 41, no. 6, pp. 954–962, 2015. View at Publisher · View at Google Scholar
  3. A. J. Copp, N. S. Adzick, L. S. Chitty, J. M. Fletcher, G. N. Holmbeck, and G. M. Shaw, “Spina bifida,” Nature Reviews Disease Primers, vol. 1, article 15007, 2015. View at Publisher · View at Google Scholar
  4. M. J. Harris and D. M. Juriloff, “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 Research Part A: Clinical and Molecular Teratology, vol. 88, no. 8, pp. 653–669, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. D. M. Juriloff and M. J. Harris, “A consideration of the evidence that genetic defects in planar cell polarity contribute to the etiology of human neural tube defects,” Birth Defects Research A—Clinical and Molecular Teratology, vol. 94, no. 10, pp. 824–840, 2012. View at Publisher · View at Google Scholar · View at Scopus
  6. N. D. E. Greene, D. Gerrelli, H. W. M. Van Straaten, and A. J. Copp, “Abnormalities of floor plate, notochord and somite differentiation in the loop-tail (LP) mouse: a model of severe neural tube defects,” Mechanisms of Development, vol. 73, no. 1, pp. 59–72, 1998. View at Publisher · View at Google Scholar · View at Scopus
  7. A. J. Copp and N. D. E. Greene, “Neural tube defects—disorders of neurulation and related embryonic processes,” Wiley Interdisciplinary Reviews: Developmental Biology, vol. 2, no. 2, pp. 213–227, 2013. View at Publisher · View at Google Scholar · View at Scopus
  8. S. Abu-Abed, P. Dollé, D. Metzger, B. Beckett, P. Chambon, and M. Petkovich, “The retinoic acid-metabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity, and development of posterior structures,” Genes and Development, vol. 15, no. 2, pp. 226–240, 2001. View at Publisher · View at Google Scholar · View at Scopus
  9. O. V. Bulgakov, J. T. Eggenschwiler, D.-H. Hong, K. V. Anderson, and T. Li, “FKBP8 is a negative regulator of mouse sonic hedgehog signaling in neural tissues,” Development, vol. 131, no. 9, pp. 2149–2159, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. C. Chiang, Y. Litingtung, E. Lee et al., “Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function,” Nature, vol. 383, no. 6599, pp. 407–413, 1996. View at Publisher · View at Google Scholar · View at Scopus
  11. Q. Ding, J. Motoyama, S. Gasca et al., “Diminished Sonic hedgehog signaling and lack of floor plate differentiation in Gli2 mutant mice,” Development, vol. 125, no. 14, pp. 2533–2543, 1998. View at Google Scholar · View at Scopus
  12. R. Lawrenson, J.-J. Wyndaele, I. Vlachonikolis, C. Farmer, and S. Glickman, “A UK general practice database study of prevalence and mortality of people with neural tube defects,” Clinical Rehabilitation, vol. 14, no. 6, pp. 627–630, 2000. View at Publisher · View at Google Scholar · View at Scopus
  13. S. E. Parker, C. T. Mai, M. A. Canfield et al., “Updated national birth prevalence estimates for selected birth defects in the United States, 2004–2006,” Birth Defects Research Part A: Clinical and Molecular Teratology, vol. 88, no. 12, pp. 1008–1016, 2010. View at Publisher · View at Google Scholar · View at Scopus
  14. N.-Y. Boo, I. G. S. Cheah, and M.-K. Thong, “Neural tube defects in malaysia: data from the malaysian national neonatal registry,” Journal of Tropical Pediatrics, vol. 59, no. 5, Article ID fmt026, pp. 338–342, 2013. View at Publisher · View at Google Scholar · View at Scopus
  15. L. Jin, L. Zhang, Z. Li, J.-M. Liu, R. Ye, and A. Ren, “Placental concentrations of mercury, lead, cadmium, and arsenic and the risk of neural tube defects in a Chinese population,” Reproductive Toxicology, vol. 35, no. 1, pp. 25–31, 2013. View at Publisher · View at Google Scholar · View at Scopus
  16. Z. Wang, S. Shangguan, X. Lu et al., “Association of SMO polymorphisms and neural tube defects in the Chinese population from Shanxi Province,” International Journal of Clinical and Experimental Medicine, vol. 6, no. 10, pp. 960–966, 2013. View at Google Scholar · View at Scopus
  17. Z. Wang, L. Wang, S. Shangguan et al., “Association between PTCH1 polymorphisms and risk of neural tube defects in a Chinese population,” Birth Defects Research Part A - Clinical and Molecular Teratology, vol. 97, no. 6, pp. 409–415, 2013. View at Publisher · View at Google Scholar · View at Scopus
  18. M. Wu, D. F. Chen, T. Sasaoka, and S. Tonegawa, “Neural tube defects and abnormal brain development in F52-deficient mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 5, pp. 2110–2115, 1996. View at Publisher · View at Google Scholar · View at Scopus
  19. S. O. Ekenze, O. V. Ajuzieogu, and B. C. Nwomeh, “Neonatal surgery in Africa: a systematic review and meta-analysis of challenges of management and outcome,” The Lancet, vol. 385, supplement 2, p. S35, 2015. View at Publisher · View at Google Scholar
  20. L. E. Mitchell, N. Scott Adzick, J. Melchionne, P. S. Pasquariello, L. N. Sutton, and A. S. Whitehead, “Spina bifida,” Lancet, vol. 364, no. 9448, pp. 1885–1895, 2004. View at Publisher · View at Google Scholar · View at Scopus
  21. R. Masson, C. H. Régnier, M.-P. Chenard et al., “Tumor necrosis factor receptor associated factor 4 (TRAF4) expression pattern during mouse development,” Mechanisms of Development, vol. 71, no. 1-2, pp. 187–191, 1998. View at Publisher · View at Google Scholar · View at Scopus
  22. A. H. Jobe, “Fetal surgery for myelomeningocele,” The New England Journal of Medicine, vol. 347, no. 4, pp. 230–231, 2002. View at Publisher · View at Google Scholar · View at Scopus
  23. G. P. Giacoia and B. Say, “Spondylocostal dysplasia and neural tube defects,” Journal of Medical Genetics, vol. 28, no. 1, pp. 51–53, 1991. View at Publisher · View at Google Scholar · View at Scopus
  24. M. M. Rodriguez, A. Mejias Jr., R. L. Haun, M. B. Mata, and J. H. Bruce, “Spondylocostal dysostosis with perinatal death and meningomyelocele,” Pediatric Pathology, vol. 14, no. 1, pp. 53–59, 1994. View at Google Scholar
  25. S. Duru, S. Ceylan, B. H. Güvenç, and S. Ceylan, “Segmental costovertebral malformations: association with neural tube defects. Report of 3 cases and review of the literature,” Pediatric Neurosurgery, vol. 30, no. 5, pp. 272–277, 1999. View at Publisher · View at Google Scholar · View at Scopus
  26. E. Kauffmann, H. Roman, G. Barau et al., “Case report: a prenatal case of Jarcho-Levin syndrome diagnosed during the first trimester of pregnancy,” Prenatal Diagnosis, vol. 23, no. 2, pp. 163–165, 2003. View at Publisher · View at Google Scholar · View at Scopus
  27. T. D. Nadkarni and H. L. Rekate, “Treatment of refractory intracranial hypertension in a spina bifida patient by a concurrent ventricular and cisterna magna-to-peritoneal shunt,” Child's Nervous System, vol. 21, no. 7, pp. 579–582, 2005. View at Publisher · View at Google Scholar · View at Scopus
  28. S. Yi, D. H. Yoon, H. C. Shin, K. N. Kim, and S. W. Lee, “A thoracic myelomeningocele in a patient with spondylocostal dysostosis. Case report,” Journal of Neurosurgery, vol. 104, no. 1, pp. 37–40, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. B. Dane, C. Dane, F. Aksoy, A. Cetin, and M. Yayla, “Jarcho-Levin syndrome presenting as neural tube defect: report of four cases and pitfalls of diagnosis,” Fetal Diagnosis and Therapy, vol. 22, no. 6, pp. 416–419, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. J. L. Tolmie, M. J. Whittle, M. B. McNay, A. A. Gibson, and J. M. Connor, “Second trimester prenatal diagnosis of the Jarcho-Levin syndrome,” Prenatal Diagnosis, vol. 7, no. 2, pp. 129–134, 1987. View at Publisher · View at Google Scholar · View at Scopus
  31. R. Romero, A. Ghidini, M. S. Eswara, M. R. Seashore, and J. C. Hobbins, “Prenatal findings in a case of spondylocostal dysplasia type I (Jarcho-Levin syndrome),” Obstetrics and Gynecology, vol. 71, no. 6, pp. 988–991, 1988. View at Google Scholar · View at Scopus
  32. R. C. M. Hennekam, F. A. Beemer, W. A. R. Huijbers, P. A. Hustinx, and F. J. van Sprang, “The cerebro-costo-mandibular syndrome: third report of familial occurrence,” Clinical Genetics, vol. 28, no. 2, pp. 118–121, 1985. View at Google Scholar · View at Scopus
  33. A. Amorosi, M. D'armiento, G. Calcagno et al., “FOXN1 homozygous mutation associated with anencephaly and severe neural tube defect in human athymic Nude/SCID fetus,” Clinical Genetics, vol. 73, no. 4, pp. 380–384, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. N. Manjunath and C. S. Vijaya Sreenivas, “New manifestations of Neu-Laxova syndrome,” American Journal of Medical Genetics, vol. 35, no. 1, pp. 55–59, 1990. View at Publisher · View at Google Scholar · View at Scopus
  35. M. E. Rode, M. T. Mennuti, R. M. Giardine, E. H. Zackai, and D. A. Driscoll, “Early ultrasound diagnosis of Neu-Laxova syndrome,” Prenatal Diagnosis, vol. 21, no. 7, pp. 575–580, 2001. View at Publisher · View at Google Scholar · View at Scopus
  36. M. J. Seller, S. Mohammed, J. Russell, and C. Ogilvie, “Microdeletion 22q11.2, Kousseff syndrome and spina bifida,” Clinical Dysmorphology, vol. 11, no. 2, pp. 113–115, 2002. View at Publisher · View at Google Scholar · View at Scopus
  37. S. Chatkupt, S. Chatkupt, and W. G. Johnson, “Waardenburg syndrome and myelomeningocele in a family,” Journal of Medical Genetics, vol. 30, no. 1, pp. 83–84, 1993. View at Publisher · View at Google Scholar · View at Scopus
  38. J. S. Nye, N. Balkin, H. Lucas, P. A. Knepper, D. G. McLone, and J. Charrow, “Myelomeningocele and Waardenburg syndrome (type 3) in patients with interstitial deletions of 2q35 and the PAX3 gene: possible digenic inheritance of a neural tube defect,” American Journal of Medical Genetics, vol. 75, no. 4, pp. 401–408, 1998. View at Publisher · View at Google Scholar · View at Scopus
  39. F. A. Hol, B. C. J. Hamel, M. P. A. Geurds et al., “A frameshift mutation in the gene for PAX3 in a girl with spina bifida and mild signs of Waardenburg syndrome,” Journal of Medical Genetics, vol. 32, no. 1, pp. 52–56, 1995. View at Publisher · View at Google Scholar · View at Scopus
  40. S. H. Shim, H. E. Wyandt, D. M. McDonald-McGinn, E. Z. Zackai, and A. Milunsky, “Molecular cytogenetic characterization of multiple intrachromosomal rearrangements of chromosome 2q in a patient with Waardenburg's syndrome and other congenital defects,” Clinical Genetics, vol. 66, no. 1, pp. 46–52, 2004. View at Publisher · View at Google Scholar · View at Scopus
  41. A. Kujat, V.-P. Veith, R. Faber, and U. G. Froster, “Prenatal diagnosis and genetic counseling in a case of spina bifida in a family with Waardenburg syndrome type I,” Fetal Diagnosis and Therapy, vol. 22, no. 2, pp. 155–158, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. S. Chatkupt, J. H. Skurnick, M. Jaggi, K. Mitruka, M. R. Koenigsberger, and W. G. Johnson, “Study of genetics, epidemiology, and vitamin usage in familial spina bifida in the united states in the 1990s,” Neurology, vol. 44, no. 1, pp. 65–70, 1994. View at Publisher · View at Google Scholar · View at Scopus
  43. P. A. Gardner and A. L. Albright, ““Like mother, like son:” hereditary anterior sacral meningocele—case report and review of the literature,” Journal of Neurosurgery, vol. 104, no. 2, pp. 138–142, 2006. View at Google Scholar · View at Scopus
  44. Z. Kibar, E. Torban, J. R. McDearmid et al., “Mutations in VANGL1 associated with neural-tube defects,” New England Journal of Medicine, vol. 356, no. 14, pp. 1432–1437, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. A. Czeizel and A. Losonci, “Split hand, obstructive urinary anomalies and spina bifida or diaphragmatic defect syndrome with autosomal dominant inheritance,” Human Genetics, vol. 77, no. 2, pp. 203–204, 1987. View at Publisher · View at Google Scholar · View at Scopus
  46. L. Almeida, K. Anyane-Yeboa, M. Grossman, and T. Rosen, “Myelomeningocele, Arnold-Chiari anomaly and hydrocephalus in focal dermal hypoplasia,” American Journal of Medical Genetics, vol. 30, no. 4, pp. 917–923, 1988. View at Publisher · View at Google Scholar · View at Scopus
  47. R. S. Mathias, R. V. Lacro, and K. L. Jones, “X-linked laterality sequence: situs inversus, complex cardiac defects, splenic defects,” American Journal of Medical Genetics, vol. 28, no. 1, pp. 111–116, 1987. View at Publisher · View at Google Scholar · View at Scopus
  48. M. Gebbia, G. B. Ferrero, G. Pilia et al., “X-linked situs abnormalities result from mutations in ZIC3,” Nature Genetics, vol. 17, no. 3, pp. 305–308, 1997. View at Publisher · View at Google Scholar · View at Scopus
  49. C. Dane, B. Dane, M. Yayla, and A. Cetin, “Prenatal diagnosis of a case of pentalogy of Cantrell with spina bifida,” Journal of Postgraduate Medicine, vol. 53, no. 2, pp. 146–148, 2007. View at Google Scholar · View at Scopus
  50. K. Nudleman, E. Andermann, F. Andermann, G. Bertrand, and E. Rogala, “The HEMI 3 syndrome. Hemihypertrophy, hemihypaesthesia, hemiareflexia and scoliosis,” Brain, vol. 107, no. 2, pp. 533–546, 1984. View at Publisher · View at Google Scholar · View at Scopus
  51. R. Sharony, S. H. Pepkowitz, H. Hixon, G. A. Machin, and J. M. Graham Jr., “Diprosopus: a pregastrulation defect involving the head, neural tube, heart, and diaphragm,” Birth Defects: Original Article Series, vol. 29, no. 1, pp. 201–209, 1993. View at Google Scholar · View at Scopus
  52. R. J. Terrafranca and A. Zellis, “Congenital hereditary cranium bifidum occultum frontalis with a review of anatomical variations in lower medsagittal region of frontal bones,” Radiology, vol. 61, no. 1, pp. 60–66, 1953. View at Publisher · View at Google Scholar · View at Scopus
  53. I. H. Tekkök, “Triple neural tube defect—cranium bifidum with rostral and caudal spina bifida—live evidence of multi-site closure of the neural tube in humans,” Child's Nervous System, vol. 21, no. 4, pp. 331–335, 2005. View at Publisher · View at Google Scholar · View at Scopus
  54. M. J. Harris and D. M. Juriloff, “Mouse mutants with neural tube closure defects and their role in understanding human neural tube defects,” Birth Defects Research A—Clinical and Molecular Teratology, vol. 79, no. 3, pp. 187–210, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. B. Franke, S. H. H. M. Vermeulen, R. P. M. Steegers-Theunissen et al., “An association study of 45 folate-related genes in spina bifida: involvement of Cubilin (CUBN) and tRNA Aspartic Acid Methyltransferase 1 (TRDMT1),” Birth Defects Research A—Clinical and Molecular Teratology, vol. 85, no. 3, pp. 216–226, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. G. M. Shaw, W. Lu, H. Zhu et al., “118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects,” BMC Medical Genetics, vol. 10, article 49, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. H. Zhu, S. Curry, S. Wen et al., “Are the betaine-homocysteine methyltransferase (BHMT and BHMT2) genes risk factors for spina bifida and orofacial clefts?” American Journal of Medical Genetics A, vol. 135, no. 3, pp. 274–277, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. J. O. Ebot Enaw, H. Zhu, W. Yang et al., “CHKA and PCYT1A gene polymorphisms, choline intake and spina bifida risk in a California population,” BMC Medicine, vol. 4, article no. 36, 2006. View at Publisher · View at Google Scholar · View at Scopus
  59. K. Doudney, J. Grinham, J. Whittaker et al., “Evaluation of folate metabolism gene polymorphisms as risk factors for open and closed neural tube defects,” American Journal of Medical Genetics, Part A, vol. 149, no. 7, pp. 1585–1589, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. V. B. O'Leary, J. L. Mills, A. Parle-McDermott et al., “Screening for new MTHFR polymorphisms and NTD risk,” American Journal of Medical Genetics Part A, vol. 138, no. 2, pp. 99–106, 2005. View at Publisher · View at Google Scholar · View at Scopus
  61. I. J. M. Van Der Linden, M. Den Heijer, L. A. Afman et al., “The methionine synthase reductase 66A>G polymorphism is a maternal risk factor for spina bifida,” Journal of Molecular Medicine, vol. 84, no. 12, pp. 1047–1054, 2006. View at Publisher · View at Google Scholar · View at Scopus
  62. I. J. M. Van Der Linden, S. G. Heil, M. Den Heijer, and H. J. Blom, “The 894G>T variant in the endothelial nitric oxide synthase gene and spina bifida risk,” Journal of Human Genetics, vol. 52, no. 6, pp. 516–520, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. K. S. Brown, M. Cook, K. Hoess, A. S. Whitehead, and L. E. Mitchell, “Evidence that the risk of spina bifida is influenced by genetic variation at the NOS3 locus,” Birth Defects Research Part A: Clinical and Molecular Teratology, vol. 70, no. 3, pp. 101–106, 2004. View at Publisher · View at Google Scholar · View at Scopus
  64. T. M. King, K.-S. Au, T. J. Kirkpatrick et al., “The impact of BRCA1 on spina bifida meningomyelocele lesion,” Annals of Human Genetics, vol. 71, no. 6, pp. 719–728, 2007. View at Publisher · View at Google Scholar · View at Scopus
  65. H. Zhu, J. O. E. Enaw, C. Ma, G. M. Shaw, E. J. Lammer, and R. H. Finnell, “Association between CFL1 gene polymorphisms and spina bifida risk in a California population,” BMC Medical Genetics, vol. 8, article 12, 2007. View at Publisher · View at Google Scholar · View at Scopus
  66. W. Lu, H. Zhu, S. Wen et al., “Screening for novel PAX3 polymorphisms and risks of spina bifida,” Birth Defects Research Part A—Clinical and Molecular Teratology, vol. 79, no. 1, pp. 45–49, 2007. View at Publisher · View at Google Scholar · View at Scopus
  67. M. Toepoel, R. P. M. Steegers-Theunissen, N. J. Ouborg et al., “Interaction of PDGFRA promoter haplotypes and maternal environmental exposures in the risk of spina bifida,” Birth Defects Research Part A - Clinical and Molecular Teratology, vol. 85, no. 7, pp. 629–636, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. K.-S. Au, H. Northrup, T. J. Kirkpatrick et al., “Promotor genotype of the platelet-derived growth factor receptor-α gene shows population stratification but not association with spina bifida meningomyelocele,” American Journal of Medical Genetics Part A, vol. 139, no. 3, pp. 194–198, 2005. View at Publisher · View at Google Scholar · View at Scopus
  69. S. Wen, W. Lu, H. Zhu et al., “Genetic polymorphisms in the thioredoxin 2 (TXN2) gene and risk for spina bifida,” American Journal of Medical Genetics A, vol. 149, no. 2, pp. 155–160, 2009. View at Publisher · View at Google Scholar · View at Scopus
  70. R. Klootwijk, P. Groenen, M. Schijvenaars et al., “Genetic variants in ZIC1, ZIC2, and ZIC3 are not major risk factors for neural tube defects in humans,” American Journal of Medical Genetics, vol. 124, no. 1, pp. 40–47, 2004. View at Google Scholar · View at Scopus
  71. I. J. M. van der Linden, U. Nguyen, S. G. Heil et al., “Variation and expression of dihydrofolate reductase (DHFR) in relation to spina bifida,” Molecular Genetics and Metabolism, vol. 91, no. 1, pp. 98–103, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. A. Parle-McDermott, F. Pangilinan, J. L. Mills et al., “The 19-bp deletion polymorphism in intron-1 of dihydrofolate reductase (DHFR) May decrease rather than increase risk for spina bifida in the Irish population,” American Journal of Medical Genetics, Part A, vol. 143, no. 11, pp. 1174–1180, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. W. G. Johnson, E. S. Stenroos, J. R. Spychala, S. Chatkupt, S. X. Ming, and S. Buyske, “New 19 bp deletion polymorphism in intron-1 of dihydrofolate reductase (DHFR): a risk factor for spina bifida acting in mothers during pregnancy?” American Journal of Medical Genetics Part A, vol. 124, no. 4, pp. 339–345, 2004. View at Google Scholar · View at Scopus
  74. N. Carroll, F. Pangilinan, A. M. Molloy et al., “Analysis of the MTHFD1 promoter and risk of neural tube defects,” Human Genetics, vol. 125, no. 3, pp. 247–256, 2009. View at Publisher · View at Google Scholar · View at Scopus
  75. P. De Marco, E. Merello, M. G. Calevo et al., “Evaluation of a methylenetetrahydrofolate-dehydrogenase 1958G > A polymorphism for neural tube defect risk,” Journal of Human Genetics, vol. 51, no. 2, pp. 98–103, 2006. View at Publisher · View at Google Scholar · View at Scopus
  76. A. Parle-McDermott, P. N. Kirke, J. L. Mills et al., “Confirmation of the R653Q polymorphism of the trifunctional C1-synthase enzyme as a maternal risk for neural tube defects in the Irish population,” European Journal of Human Genetics, vol. 14, no. 6, pp. 768–772, 2006. View at Publisher · View at Google Scholar · View at Scopus
  77. E. Grandone, A. M. Corrao, D. Colaizzo et al., “Homocysteine metabolism in families from southern Italy with neural tube defects: role of genetic and nutritional determinants,” Prenatal Diagnosis, vol. 26, no. 1, pp. 1–5, 2006. View at Publisher · View at Google Scholar · View at Scopus
  78. L. Gonzalez-Herrera, I. Castillo-Zapata, G. Garcia-Escalante, and D. Pinto-Escalante, “A1298C polymorphism of the MTHFR gene and neural tube defects in the state of Yucatan, Mexico,” Birth Defects Research Part A: Clinical and Molecular Teratology, vol. 79, no. 8, pp. 622–626, 2007. View at Publisher · View at Google Scholar · View at Scopus
  79. K. A. Volcik, G. M. Shaw, H. Zhu, E. J. Lammer, C. Laurent, and R. H. Finnell, “Associations between polymorphisms within the thymidylate synthase gene and spina bifida,” Birth Defects Research Part A: Clinical and Molecular Teratology, vol. 67, no. 11, pp. 924–928, 2003. View at Publisher · View at Google Scholar · View at Scopus
  80. C. M. Davidson, H. Northrup, T. M. King et al., “Genes in glucose metabolism and association with spina bifida,” Reproductive Sciences, vol. 15, no. 1, pp. 51–58, 2008. View at Publisher · View at Google Scholar · View at Scopus
  81. A. F. Olshan, G. M. Shaw, R. C. Millikan, C. Laurent, and R. H. Finnell, “Polymorphisms in DNA repair genes as risk factors for spina bifida and orofacial clefts,” American Journal of Medical Genetics, vol. 135, no. 3, pp. 268–273, 2005. View at Publisher · View at Google Scholar · View at Scopus
  82. K. Doudney, G. E. Moore, P. Stanier et al., “Analysis of the planar cell polarity gene Vangl2 and its co-expressed paralogue Vangl1 in neural tube defect patients,” American Journal of Medical Genetics, vol. 136, no. 1, pp. 90–92, 2005. View at Publisher · View at Google Scholar · View at Scopus
  83. Z. Kibar, C. M. Bosoi, M. Kooistra et al., “Novel mutations in VANGL1 in neural tube defects,” Human Mutation, vol. 30, no. 7, pp. E706–E715, 2009. View at Publisher · View at Google Scholar · View at Scopus
  84. Y. Lei, H. Zhu, W. Yang, M. E. Ross, G. M. Shaw, and R. H. Finnell, “Identification of novel CELSR1 mutations in spina bifida,” PLoS ONE, vol. 9, no. 3, Article ID e92207, 2014. View at Publisher · View at Google Scholar · View at Scopus
  85. Y. Lei, H. Zhu, C. Duhon et al., “Mutations in planar cell polarity gene SCRIB are associated with spina bifida,” PLoS ONE, vol. 8, no. 7, Article ID e69262, 2013. View at Publisher · View at Google Scholar · View at Scopus
  86. S. Chen, Q. Zhang, B. Bai et al., “MARK2/Par1b insufficiency attenuates DVL gene transcription via histone deacetylation in lumbosacral spina bifida,” Molecular Neurobiology, 2016. View at Publisher · View at Google Scholar
  87. K. L. Deak, M. E. Dickerson, E. Linney et al., “Analysis of ALDH1A2, CYP26A1, CYP26B1, CRABP1, and CRABP2 in human neural tube defects suggests a possible association with alleles in ALDH1A2,” Birth Defects Research A—Clinical and Molecular Teratology, vol. 73, no. 11, pp. 868–875, 2005. View at Publisher · View at Google Scholar · View at Scopus
  88. L. E. Jensen, S. Barbaux, K. Hoess, S. Fraterman, A. S. Whitehead, and L. E. Mitchell, “The human T locus and spina bifida risk,” Human Genetics, vol. 115, no. 6, pp. 475–482, 2004. View at Publisher · View at Google Scholar · View at Scopus
  89. H. Zhu, W. Yang, W. Lu et al., “A known functional polymorphism (Ile120Val) of the human PCMT1 gene and risk of spina bifida,” Molecular Genetics and Metabolism, vol. 87, no. 1, pp. 66–70, 2006. View at Publisher · View at Google Scholar · View at Scopus
  90. B. A. Kase, H. Northrup, A. C. Morrison et al., “Association of copper-zinc superoxide dismutase (SOD1) and manganese superoxide dismutase (SOD2) genes with nonsyndromic myelomeningocele,” Birth Defects Research Part A: Clinical and Molecular Teratology, vol. 94, no. 10, pp. 762–769, 2012. View at Publisher · View at Google Scholar · View at Scopus
  91. A. Robinson, D. Partridge, A. Malhas et al., “Is LMNB1 a susceptibility gene for neural tube defects in humans?” Birth Defects Research A—Clinical and Molecular Teratology, vol. 97, no. 6, pp. 398–402, 2013. View at Publisher · View at Google Scholar · View at Scopus
  92. K. L. Deak, A. L. Boyles, H. C. Etchevers et al., “SNPs in the neural cell adhesion molecule 1 gene (NCAM1) may be associated with human neural tube defects,” Human Genetics, vol. 117, no. 2-3, pp. 133–142, 2005. View at Publisher · View at Google Scholar · View at Scopus
  93. N. D. E. Greene, P. Stanier, and A. J. Copp, “Genetics of human neural tube defects,” Human Molecular Genetics, vol. 18, no. 2, pp. R113–R129, 2009. View at Publisher · View at Google Scholar · View at Scopus
  94. C. Deng, M. Bedford, C. Li et al., “Fibroblast growth factor receptor-1 (FGFR-1) is essential for normal neural tube and limb development,” Developmental Biology, vol. 185, no. 1, pp. 42–54, 1997. View at Publisher · View at Google Scholar · View at Scopus
  95. C. H. Régnier, R. Masson, V. Kedinger et al., “Impaired neural tube closure, axial skeleton malformations, and tracheal ring disruption in TRAF4-deficient mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 8, pp. 5585–5590, 2002. View at Publisher · View at Google Scholar · View at Scopus
  96. T. M. Saxton and T. Pawson, “Morphogenetic movements at gastrulation require the SH2 tyrosine phosphatase Shp2,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 7, pp. 3790–3795, 1999. View at Publisher · View at Google Scholar · View at Scopus
  97. F. B. Essien, M. B. Haviland, and A. E. Naidoff, “Expression of a new mutation (Axd) causing axial defects in mice correlates with maternal phenotype and age,” Teratology, vol. 42, no. 2, pp. 183–194, 1990. View at Publisher · View at Google Scholar · View at Scopus
  98. B. Nait-Oumesmar, B. Stecca, G. Fatterpekar, T. Naidich, J. Corbin, and R. A. Lazzarini, “Ectopic expression of Gcm1 induces congenital spinal cord abnormalities,” Development, vol. 129, no. 16, pp. 3957–3964, 2002. View at Google Scholar · View at Scopus
  99. D. B. Wilson and D. P. Wyatt, “Pathogenesis of neural dysraphism in the mouse mutant vacuolated lens (vl),” Journal of Neuropathology and Experimental Neurology, vol. 45, no. 1, pp. 43–55, 1986. View at Publisher · View at Google Scholar · View at Scopus
  100. J. Qu, X. Li, B. G. Novitch et al., “PAK4 kinase is essential for embryonic viability and for proper neuronal development,” Molecular and Cellular Biology, vol. 23, no. 20, pp. 7122–7133, 2003. View at Publisher · View at Google Scholar · View at Scopus
  101. C. Naruse-Nakajima, M. Asano, and Y. Iwakura, “Involvement of EphA2 in the formation of the tail notochord via interaction with ephrinA1,” Mechanisms of Development, vol. 102, no. 1-2, pp. 95–105, 2001. View at Publisher · View at Google Scholar · View at Scopus
  102. S. B. Snapper, F. Takeshima, I. Antón et al., “N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility,” Nature Cell Biology, vol. 3, no. 10, pp. 897–904, 2001. View at Publisher · View at Google Scholar · View at Scopus
  103. W. Xu, H. Baribault, and E. D. Adamson, “Vinculin knockout results in heart and brain defects during embryonic development,” Development, vol. 125, no. 2, pp. 327–337, 1998. View at Google Scholar · View at Scopus
  104. P. Elms, P. Siggers, D. Napper, A. Greenfield, and R. Arkell, “Zic2 is required for neural crest formation and hindbrain patterning during mouse development,” Developmental Biology, vol. 264, no. 2, pp. 391–406, 2003. View at Publisher · View at Google Scholar · View at Scopus
  105. Z. Kibar, K. J. Vogan, N. Groulx, M. J. Justice, D. A. Underhill, and P. Gros, “Ltap, a mammalian homolog of Drosophila Strabismus/Van Gogh, is altered in the mouse neural tube mutant Loop-tail,” Nature Genetics, vol. 28, no. 3, pp. 251–255, 2001. View at Publisher · View at Google Scholar · View at Scopus
  106. S.-L. Ang and J. Rossant, “HNF-3β is essential for node and notochord formation in mouse development,” Cell, vol. 78, no. 4, pp. 561–574, 1994. View at Publisher · View at Google Scholar · View at Scopus
  107. K. Doudney and P. Stanier, “Epithelial cell polarity genes are required for neural tube closure,” American Journal of Medical Genetics - Seminars in Medical Genetics, vol. 135, no. 1, pp. 42–47, 2005. View at Publisher · View at Google Scholar · View at Scopus
  108. J. Galceran, I. Fariñas, M. J. Depew, H. Clevers, and R. Grosschedl, “Wnt3a−/−-like phenotype and limb deficiency in Lef1−/−Tcf1−/− mice,” Genes and Development, vol. 13, no. 6, pp. 709–717, 1999. View at Publisher · View at Google Scholar · View at Scopus
  109. S. Abu-Abed, P. Dollé, D. Metzger et al., “Developing with lethal RA levels: genetic ablation of Rarg can restore the viability of mice lacking Cyp26a1,” Development, vol. 130, no. 7, pp. 1449–1459, 2003. View at Publisher · View at Google Scholar · View at Scopus
  110. H. Chi, M. R. Sarkisian, P. Rakic, and R. A. Flavell, “Loss of mitogen-activated protein kinase kinase kinase 4 (MEKK4) results in enhanced apoptosis and defective neural tube development,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 10, pp. 3846–3851, 2005. View at Publisher · View at Google Scholar · View at Scopus
  111. J. Chen, S. Chang, S. A. Duncan, H. J. Okano, G. Fishell, and A. Aderem, “Disruption of the MacMARCKS gene prevents cranial neural tube closure and results in anencephaly,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 13, pp. 6275–6279, 1996. View at Publisher · View at Google Scholar · View at Scopus
  112. M. J. Solloway and E. J. Robertson, “Early embryonic lethality in Bmp5;Bmp7 double mutant mice suggests functional redundancy within the 60A subgroup,” Development, vol. 126, no. 8, pp. 1753–1768, 1999. View at Google Scholar · View at Scopus
  113. E. Martí, R. Takada, D. A. Bumcrot, H. Sasaki, and A. P. McMahon, “Distribution of Sonic hedgehog peptides in the developing chick and mouse embryo,” Development, vol. 121, no. 8, pp. 2537–2547, 1995. View at Google Scholar · View at Scopus
  114. D. C. Weinstein, A. Ruiz i Altaba, W. S. Chen et al., “The winged-helix transcription factor HNF-3β is required for notochord development in the mouse embryo,” Cell, vol. 78, no. 4, pp. 575–588, 1994. View at Publisher · View at Google Scholar · View at Scopus
  115. J. Dubrulle and O. Pourquié, “fgf8 mRNA decay establishes a gradient that couples axial elongation to patterning in the vertebrate embryo,” Nature, vol. 427, no. 6973, pp. 419–422, 2004. View at Publisher · View at Google Scholar · View at Scopus
  116. A. Auden, J. Caddy, T. Wilanowski, S. B. Ting, J. M. Cunningham, and S. M. Jane, “Spatial and temporal expression of the Grainyhead-like transcription factor family during murine development,” Gene Expression Patterns, vol. 6, no. 8, pp. 964–970, 2006. View at Publisher · View at Google Scholar · View at Scopus
  117. E.-H. Jho, T. Zhang, C. Domon, C.-K. Joo, J.-N. Freund, and F. Costantini, “Wnt/β-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway,” Molecular and Cellular Biology, vol. 22, no. 4, pp. 1172–1183, 2002. View at Publisher · View at Google Scholar · View at Scopus
  118. M. D. Goulding, G. Chalepakis, U. Deutsch, J. R. Erselius, and P. Gruss, “Pax-3, a novel murine DNA binding protein expressed during early neurogenesis,” EMBO Journal, vol. 10, no. 5, pp. 1135–1147, 1991. View at Google Scholar · View at Scopus
  119. C. Ramos and B. Robert, “msh/Msx gene family in neural development,” Trends in Genetics, vol. 21, no. 11, pp. 624–632, 2005. View at Publisher · View at Google Scholar · View at Scopus
  120. E. Camerer, A. Barker, D. N. Duong et al., “Local protease signaling contributes to neural tube closure in the mouse embryo,” Developmental Cell, vol. 18, no. 1, pp. 25–38, 2010. View at Publisher · View at Google Scholar · View at Scopus
  121. N. M. J. Van Der Put, H. W. M. Van Straaten, F. J. M. Trijbels, and H. J. Blom, “Folate, homocysteine and neural tube defects: an overview,” Experimental Biology and Medicine, vol. 226, no. 4, pp. 243–270, 2001. View at Google Scholar · View at Scopus
  122. P. Tortori-Donati, A. Rossi, and A. Cama, “Spinal dysraphism: a review of neuroradiological features with embryological correlations and proposal for a new classification,” Neuroradiology, vol. 42, no. 7, pp. 471–491, 2000. View at Publisher · View at Google Scholar · View at Scopus
  123. J. J. Volpe, Neurology of the Newborn, Saunders, Philadelphia, Pa, USA, 1995.
  124. K. L. Stevenson, “Chiari type II malformation: past, present, and future,” Neurosurgical focus, vol. 16, no. 2, article E5, 2004. View at Google Scholar · View at Scopus
  125. H. Williams, “A unifying hypothesis for hydrocephalus, Chiari malformation, syringomyelia, anencephaly and spina bifida,” Cerebrospinal Fluid Research, vol. 5, article 7, 2008. View at Publisher · View at Google Scholar · View at Scopus
  126. B. G. Coleman, N. S. Adzick, T. M. Crombleholme et al., “Fetal therapy: state of the art,” Journal of Ultrasound in Medicine, vol. 21, no. 11, pp. 1257–1288, 2002. View at Google Scholar · View at Scopus
  127. N. S. Adzick, L. N. Sutton, T. M. Crombleholme, and A. W. Flake, “Successful fetal surgery for spina bifida,” Lancet, vol. 352, no. 9141, pp. 1675–1676, 1998. View at Publisher · View at Google Scholar · View at Scopus
  128. N. S. Adzick, E. A. Thom, C. Y. Spong et al., “A randomized trial of prenatal versus postnatal repair of myelomeningocele,” New England Journal of Medicine, vol. 364, no. 11, pp. 993–1004, 2011. View at Publisher · View at Google Scholar · View at Scopus
  129. J. D. Eubanks and V. K. Cheruvu, “Prevalence of sacral spina bifida occulta and its relationship to age, sex, race, and the sacral table angle: an anatomic, osteologic study of three thousand one hundred specimens,” Spine, vol. 34, no. 15, pp. 1539–1543, 2009. View at Publisher · View at Google Scholar · View at Scopus
  130. A. Fidas, H. L. MacDonald, R. A. Elton, S. R. Wild, G. D. Chisholm, and R. Scott, “Prevalence and patterns of spina bifida occulta in 2707 normal adults,” Clinical Radiology, vol. 38, no. 5, pp. 537–542, 1987. View at Publisher · View at Google Scholar · View at Scopus
  131. L. May, R. Hayward, A. Chakraborty et al., “Lack of uniformity in the clinical assessment of children with lipomyelomeningocele: a review of the literature and recommendations for the future,” Child's Nervous System, vol. 29, no. 6, pp. 961–970, 2013. View at Publisher · View at Google Scholar · View at Scopus
  132. N. K. Venkataramana, “Spinal dysraphism,” Journal of Pediatric Neurosciences, vol. 6, no. 3, pp. S31–S40, 2011. View at Publisher · View at Google Scholar · View at Scopus
  133. B. J. Iskandar, B. B. Fulmer, M. N. Hadley, and W. J. Oakes, “Congenital tethered spinal cord syndrome in adults,” Journal of Neurosurgery, vol. 88, no. 6, pp. 958–961, 1998. View at Publisher · View at Google Scholar · View at Scopus
  134. J. Lorber, “Selective treatment of myelomeningocele: to treat or not to treat?” Pediatrics, vol. 53, no. 3, pp. 307–308, 1974. View at Google Scholar · View at Scopus
  135. J. P. Bruner and N. Tulipan, “Intrauterine repair of spina bifida,” Clinical Obstetrics and Gynecology, vol. 48, no. 4, pp. 942–955, 2005. View at Publisher · View at Google Scholar · View at Scopus
  136. J. H. Piatt Jr., “Treatment of myelomeningocele: a review of outcomes and continuing neurosurgical considerations among adults—a review,” Journal of Neurosurgery: Pediatrics, vol. 6, no. 6, pp. 515–525, 2010. View at Publisher · View at Google Scholar · View at Scopus
  137. R. M. Bowman, D. G. McLone, J. A. Grant, T. Tomita, and J. A. Ito, “Spina bifida outcome: a 25-year prospective,” Pediatric Neurosurgery, vol. 34, no. 3, pp. 114–120, 2001. View at Publisher · View at Google Scholar · View at Scopus
  138. R. Lawrenson, J.-J. Wyndaele, I. Vlachonikolis, C. Farmer, and S. Glickman, “Renal failure in patients with neurogenic lower urinary tract dysfunction,” Neuroepidemiology, vol. 20, no. 2, pp. 138–143, 2001. View at Publisher · View at Google Scholar · View at Scopus
  139. H. T. Ireys, G. F. Anderson, T. J. Shaffer, and J. M. Neff, “Expenditures for care of children with chronic illnesses enrolled in the Washington State Medicaid Program, fiscal year 1993,” Pediatrics, vol. 100, no. 2, pp. 197–204, 1997. View at Publisher · View at Google Scholar · View at Scopus
  140. M. M. Macias, K. M. Roberts, C. F. Saylor, and J. J. Fussell, “Toileting concerns, parenting stress, and behavior problems in children with special health care needs,” Clinical Pediatrics, vol. 45, no. 5, pp. 415–422, 2006. View at Publisher · View at Google Scholar · View at Scopus
  141. M. Verhoef, H. A. Barf, M. W. M. Post, F. W. A. van Asbeck, R. H. J. M. Gooskens, and A. J. H. Prevo, “Functional independence among young adults with spina bifida, in relation to hydrocephalus and level of lesion,” Developmental Medicine and Child Neurology, vol. 48, no. 2, pp. 114–119, 2006. View at Publisher · View at Google Scholar · View at Scopus
  142. A. H. Sin, M. Rashidi, G. Caldito, and A. Nanda, “Surgical treatment of myelomeningocele: year 2000 hospitalization, outcome, and cost analysis in the US,” Child's Nervous System, vol. 23, no. 10, pp. 1125–1127, 2007. View at Publisher · View at Google Scholar · View at Scopus
  143. C.-P. Chen, “Syndromes, disorders and maternal risk factors associated with neural tube defects (I),” Taiwanese Journal of Obstetrics and Gynecology, vol. 47, no. 1, pp. 1–9, 2008. View at Publisher · View at Google Scholar · View at Scopus
  144. J. Hall and F. Solehdin, “Folic acid for the prevention of congenital anomalies,” European Journal of Pediatrics, vol. 157, no. 6, pp. 445–450, 1998. View at Publisher · View at Google Scholar · View at Scopus
  145. L. H. Seaver and R. E. Stevenson, “Syndromes with neural tube defects,” in Neural Tube Defects: From Origin to Treatment, D. F. Wyszynski, Ed., Oxford University Press, Oxford, UK, 2006. View at Google Scholar
  146. M. Z. Seidahmed, O. B. Abdelbasit, M. M. Shaheed et al., “Epidemiology of neural tube defects,” Saudi Medical Journal, vol. 35, supplement 1, pp. S29–S35, 2014. View at Google Scholar
  147. L. B. Holmes, S. G. Driscoll, and L. Atkins, “Etiologic heterogeneity of neural-tube defects,” New England Journal of Medicine, vol. 294, no. 7, pp. 365–369, 1976. View at Publisher · View at Google Scholar · View at Scopus
  148. M. J. Khoury, J. D. Erickson, and L. M. James, “Etiologic heterogeneity of neural tube defects: clues from epidemiology,” American Journal of Epidemiology, vol. 115, no. 4, pp. 538–548, 1982. View at Google Scholar · View at Scopus
  149. M. J. Khoury, J. David Erickson, and L. M. James, “Etiologic heterogeneity of neural tube defects. II. Clues from family studies,” American Journal of Human Genetics, vol. 34, no. 6, pp. 980–987, 1982. View at Google Scholar · View at Scopus
  150. R. A. Martin, R. M. Fineman, and L. B. Jorde, “Phenotypic heterogeneity in neural tube defects: a clue to causal heterogeneity,” American Journal of Medical Genetics, vol. 16, no. 4, pp. 519–525, 1983. View at Publisher · View at Google Scholar · View at Scopus
  151. E. Rampersaud, E. C. Melvin, and M. C. Speer, Neural Tube Defects: From Origin to Treatment, Oxford University Press, 2006.
  152. M. J. Aguiar, A. S. Campos, R. A. Aguiar, A. M. Lana, R. L. Magalhaes, and L. T. Babeto, “Neural tube defects and associated factors in liveborn and stillborn infants,” Jornal de Pediatria (Rio de Janeiro), vol. 79, no. 2, pp. 129–134, 2003. View at Google Scholar
  153. J. Dietl, “Maternal obesity and complications during pregnancy,” Journal of Perinatal Medicine, vol. 33, no. 2, pp. 100–105, 2005. View at Publisher · View at Google Scholar · View at Scopus
  154. L. F. Hall and A. G. Neubert, “Obesity and pregnancy,” Obstetrical and Gynecological Survey, vol. 60, no. 4, pp. 253–260, 2005. View at Publisher · View at Google Scholar · View at Scopus
  155. R. Mojtabai, “Body mass index and serum folate in childbearing age women,” European Journal of Epidemiology, vol. 19, no. 11, pp. 1029–1036, 2004. View at Publisher · View at Google Scholar · View at Scopus
  156. K. R. Andreasen, M. L. Andersen, and A. L. Schantz, “Obesity and pregnancy,” Acta Obstetricia et Gynecologica Scandinavica, vol. 83, no. 11, pp. 1022–1029, 2004. View at Publisher · View at Google Scholar · View at Scopus
  157. D. K. Waller, J. L. Mills, J. L. Simpson et al., “Are obese women at higher risk for producing malformed offspring?” American Journal of Obstetrics and Gynecology, vol. 170, no. 2, pp. 541–548, 1994. View at Publisher · View at Google Scholar · View at Scopus
  158. S. A. Rasmussen, S. Y. Chu, S. Y. Kim, C. H. Schmid, and J. Lau, “Maternal obesity and risk of neural tube defects: a metaanalysis,” American Journal of Obstetrics and Gynecology, vol. 198, no. 6, pp. 611–619, 2008. View at Publisher · View at Google Scholar · View at Scopus
  159. L. E. Jensen, K. Hoess, A. S. Whitehead, and L. E. Mitchell, “The NAT1 C1095A polymorphism, maternal multivitamin use and smoking, and the risk of spina bifida,” Birth Defects Research Part A: Clinical and Molecular Teratology, vol. 73, no. 7, pp. 512–516, 2005. View at Publisher · View at Google Scholar · View at Scopus
  160. L. Suarez, T. Ramadhani, M. Felkner et al., “Maternal smoking, passive tobacco smoke, and neural tube defects,” Birth Defects Research Part A - Clinical and Molecular Teratology, vol. 91, no. 1, pp. 29–33, 2011. View at Publisher · View at Google Scholar · View at Scopus
  161. L. Wang, L. Jin, J. Liu et al., “Maternal genetic polymorphisms of phase II metabolic enzymes and the risk of fetal neural tube defects,” Birth Defects Research Part A: Clinical and Molecular Teratology, vol. 100, no. 1, pp. 13–21, 2014. View at Publisher · View at Google Scholar · View at Scopus
  162. A. Ornoy, “Neuroteratogens in man: an overview with special emphasis on the teratogenicity of antiepileptic drugs in pregnancy,” Reproductive Toxicology, vol. 22, no. 2, pp. 214–226, 2006. View at Publisher · View at Google Scholar · View at Scopus
  163. M. S. Yerby, “Management issues for women with epilepsy: neural tube defects and folic acid supplementation,” Neurology, vol. 61, no. 6, pp. S23–S26, 2003. View at Publisher · View at Google Scholar · View at Scopus
  164. M. M. Werler, K. A. Ahrens, J. L. F. Bosco et al., “Use of antiepileptic medications in pregnancy in relation to risks of birth defects,” Annals of Epidemiology, vol. 21, no. 11, pp. 842–850, 2011. View at Publisher · View at Google Scholar · View at Scopus
  165. E. L. Fine, M. Horal, T. I. Chang, G. Fortin, and M. R. Loeken, “Evidence that elevated glucose causes altered gene expression, apoptosis, and neural tube defects in a mouse model of diabetic pregnancy,” Diabetes, vol. 48, no. 12, pp. 2454–2462, 1999. View at Publisher · View at Google Scholar · View at Scopus
  166. L. Pani, M. Horal, and M. R. Loeken, “Polymorphic susceptibility to the molecular causes of neural tube defects during diabetic embryopathy,” Diabetes, vol. 51, no. 9, pp. 2871–2874, 2002. View at Publisher · View at Google Scholar · View at Scopus
  167. M. E. Moretti, B. Bar-Oz, S. Fried, and G. Koren, “Maternal hyperthermia and the risk for neural tube defects in offspring: systematic review and meta-analysis,” Epidemiology, vol. 16, no. 2, pp. 216–219, 2005. View at Publisher · View at Google Scholar · View at Scopus
  168. B.-F. Hwang, P. Magnus, and J. J. K. Jaakkola, “Risk of specific birth defects in relation to chlorination and the amount of natural organic matter in the water supply,” American Journal of Epidemiology, vol. 156, no. 4, pp. 374–382, 2002. View at Publisher · View at Google Scholar · View at Scopus
  169. F. Bove, Y. Shim, and P. Zeitz, “Drinking water contaminants and adverse pregnancy outcomes: a review,” Environmental Health Perspectives, vol. 110, supplement 1, pp. 61–74, 2002. View at Publisher · View at Google Scholar · View at Scopus
  170. C. G. Graves, G. M. Matanoski, and R. G. Tardiff, “Weight of evidence for an association between adverse reproductive and developmental effects and exposure to disinfection by-products: a critical review,” Regulatory Toxicology and Pharmacology, vol. 34, no. 2, pp. 103–124, 2001. View at Publisher · View at Google Scholar · View at Scopus
  171. P. Cavalli and A. J. Copp, “Inositol and folate resistant neural tube defects,” Journal of medical genetics, vol. 39, no. 2, p. E5, 2002. View at Publisher · View at Google Scholar · View at Scopus
  172. G. M. Shaw, T. Quach, V. Nelson et al., “Neural tube defects associated with maternal periconceptional dietary intake of simple sugars and glycemic index,” The American Journal of Clinical Nutrition, vol. 78, no. 5, pp. 972–978, 2003. View at Google Scholar · View at Scopus
  173. C. Ulman, F. Taneli, F. Oksel, and H. Hakerlerler, “Zinc-deficient sprouting blight potatoes and their possible relation with neural tube defects,” Cell Biochemistry and Function, vol. 23, no. 1, pp. 69–72, 2005. View at Publisher · View at Google Scholar · View at Scopus
  174. I. Martín, M. J. Gibert, C. Pintos, A. Noguera, A. Besalduch, and A. Obrador, “Oxidative stress in mothers who have conceived fetus with neural tube defects: the role of aminothiols and selenium,” Clinical Nutrition, vol. 23, no. 4, pp. 507–514, 2004. View at Publisher · View at Google Scholar · View at Scopus
  175. P. M. W. Groenen, I. A. L. M. Van Rooij, P. G. M. Peer, R. H. Gooskens, G. A. Zielhuis, and R. P. M. Steegers-Theunissen, “Marginal maternal vitamin B 12 status increases the risk of offspring with spina bifida,” American Journal of Obstetrics and Gynecology, vol. 191, no. 1, pp. 11–17, 2004. View at Publisher · View at Google Scholar · View at Scopus
  176. B. Cengiz, F. Söylemez, E. Öztürk, and A. O. Çavdar, “Serum zinc, selenium, copper, and lead levels in women with second-trimester induced abortion resulting from neural tube defects: a preliminary study,” Biological Trace Element Research, vol. 97, no. 3, pp. 225–235, 2004. View at Publisher · View at Google Scholar · View at Scopus
  177. J. P. Harmon, A. K. Hiett, C. G. Palmer, and A. M. Golichowski, “Prenatal ultrasound detection of isolated neural tube defects: is cytogenetic evaluation warranted?” Obstetrics and Gynecology, vol. 86, no. 4, pp. 595–599, 1995. View at Publisher · View at Google Scholar · View at Scopus
  178. R. F. Hume Jr., A. Drugan, A. Reichler et al., “Aneuploidy among prenatally detected neural tube defects,” American Journal of Medical Genetics, vol. 61, no. 2, pp. 171–173, 1996. View at Publisher · View at Google Scholar · View at Scopus
  179. W. Coerdt, K. Miller, W. Holzgreve, R. Rauskolb, E. Schwinger, and H. Rehder, “Neural tube defects in chromosomally normal and abnormal human embryos,” Ultrasound in Obstetrics and Gynecology, vol. 10, no. 6, pp. 410–415, 1997. View at Publisher · View at Google Scholar · View at Scopus
  180. J. S. Dashe, D. M. Twickler, R. Santos-Ramos, D. D. McIntire, and R. M. Ramus, “Alpha-fetoprotein detection of neural tube defects and the impact of standard ultrasound,” American Journal of Obstetrics and Gynecology, vol. 195, no. 6, pp. 1623–1628, 2006. View at Publisher · View at Google Scholar · View at Scopus
  181. N. Wald and A. Hackshaw, “Folic acid and prevention of neural-tube defects,” The Lancet, vol. 350, no. 9078, article no. 665, 1997. View at Google Scholar · View at Scopus
  182. Z. Alfirevic, “DISQ 3: failure to diagnose a fetal anomaly on a routine ultrasound scan at 20 weeks,” Ultrasound in Obstetrics and Gynecology, vol. 26, no. 7, pp. 797–798, 2005. View at Publisher · View at Google Scholar · View at Scopus
  183. E. Garne, M. Loane, H. Dolk et al., “Prenatal diagnosis of severe structural congenital malformations in Europe,” Ultrasound in Obstetrics and Gynecology, vol. 25, no. 1, pp. 6–11, 2005. View at Publisher · View at Google Scholar · View at Scopus
  184. MRC Vitamin Study Research Group, “Prevention of neural tube defects: results of the Medical Research Council Vitamin Study,” The Lancet, vol. 338, no. 8760, pp. 131–137, 1991. View at Publisher · View at Google Scholar
  185. A. E. Czeizel and I. Dudás, “Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation,” The New England Journal of Medicine, vol. 327, no. 26, pp. 1832–1835, 1992. View at Publisher · View at Google Scholar · View at Scopus
  186. N. D. E. Greene and A. J. Copp, “Inositol prevents folate-resistant neural tube defects in the mouse,” Nature Medicine, vol. 3, no. 1, pp. 60–66, 1997. View at Publisher · View at Google Scholar · View at Scopus
  187. N. D. Greene, K. Y. Leung, V. Gay et al., “Inositol for the prevention of neural tube defects: a pilot randomised controlled trial,” British Journal of Nutrition, vol. 115, pp. 974–983, 2016. View at Google Scholar
  188. S. Bolusani, B. A. Young, N. A. Cole et al., “Mammalian MTHFD2L encodes a mitochondrial methylenetetrahydrofolate dehydrogenase isozyme expressed in adult tissues,” Journal of Biological Chemistry, vol. 286, no. 7, pp. 5166–5174, 2011. View at Publisher · View at Google Scholar · View at Scopus
  189. J. Momb, J. P. Lewandowski, J. D. Bryant et al., “Deletion of Mthfd1l causes embryonic lethality and neural tube and craniofacial defects in mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 2, pp. 549–554, 2013. View at Publisher · View at Google Scholar · View at Scopus
  190. Y. J. Pai, K.-Y. Leung, D. Savery et al., “Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice,” Nature Communications, vol. 6, article no. 6388, 2015. View at Publisher · View at Google Scholar · View at Scopus
  191. R. L. Agag, M. S. Granick, M. Omidi et al., “Neurosurgical reconstruction with acellular cadaveric dermal matrix,” Annals of Plastic Surgery, vol. 52, no. 6, pp. 571–577, 2004. View at Publisher · View at Google Scholar · View at Scopus
  192. M. Watanabe, H. Li, A. G. Kim et al., “Complete tissue coverage achieved by scaffold-based tissue engineering in the fetal sheep model of Myelomeningocele,” Biomaterials, vol. 76, pp. 133–143, 2016. View at Publisher · View at Google Scholar
  193. Z. Kmietowicz, “Plymouth mother is first UK woman to have prenatal repair of open spina bifida funded by NHS,” British Medical Journal, vol. 349, Article ID g6875, 2014. View at Publisher · View at Google Scholar · View at Scopus
  194. D. Stiefel, A. J. Copp, and M. Meuli, “Fetal spina bifida in a mouse model: loss of neural function in utero,” Journal of Neurosurgery, vol. 106, no. 3, pp. 213–221, 2007. View at Google Scholar · View at Scopus
  195. M. Meuli, C. Meuli-Simmen, C. D. Yingling et al., “Creation of myelomeningocele in utero: a model of functional damage from spinal cord exposure in fetal sheep,” Journal of Pediatric Surgery, vol. 30, no. 7, pp. 1028–1033, 1995. View at Publisher · View at Google Scholar · View at Scopus
  196. D. S. Heffez, J. Aryanpur, G. M. Hutchins, and J. M. Freeman, “The paralysis associated with myelomeningocele: clinical and experimental data implicating a preventable spinal cord injury,” Neurosurgery, vol. 26, no. 6, pp. 987–992, 1990. View at Publisher · View at Google Scholar · View at Scopus
  197. D. S. Heffez, J. Aryanpur, N. A. C. Rotellini et al., “Intrauterine repair of experimental surgically created dysraphism,” Neurosurgery, vol. 32, no. 6, pp. 1005–1010, 1993. View at Publisher · View at Google Scholar · View at Scopus
  198. M. Meuli, C. Meuli-Simmen, G. M. Hutchins et al., “In utero surgery rescues neurological function at birth in sheep with spina bifida,” Nature Medicine, vol. 1, no. 4, pp. 342–347, 1995. View at Publisher · View at Google Scholar · View at Scopus
  199. N. Tulipan, J. P. Bruner, M. Hernanz-Schulman et al., “Effect of intrauterine myelomeningocele repair on central nervous system structure and function,” Pediatric Neurosurgery, vol. 31, no. 4, pp. 183–188, 1999. View at Publisher · View at Google Scholar · View at Scopus
  200. Y. Yi, M. Lindemann, A. Colligs, and C. Snowball, “Economic burden of neural tube defects and impact of prevention with folic acid: a literature review,” European Journal of Pediatrics, vol. 170, no. 11, pp. 1391–1400, 2011. View at Publisher · View at Google Scholar · View at Scopus
  201. S. Chatkupt, F. A. Hol, Y. Y. Shugart et al., “Absence of linkage between familial neural tube defects and PAX3 gene,” Journal of Medical Genetics, vol. 32, no. 3, pp. 200–204, 1995. View at Publisher · View at Google Scholar · View at Scopus
  202. S. Hanaei, F. Nejat, A. Mortazavi, Z. Habibi, A. Esmaeili, and M. El Khashab, “Identical twins with lumbosacral lipomyelomeningocele,” Journal of neurosurgery. Pediatrics, vol. 15, no. 1, pp. 92–95, 2015. View at Publisher · View at Google Scholar · View at Scopus
  203. M. R. Amorim, M. A. C. Lima, E. E. Castilla, and I. M. Orioli, “Non-Latin European descent could be a requirement for association of NTDs and MTHFR variant 677C > T: a meta-analysis,” American Journal of Medical Genetics Part A, vol. 143, no. 15, pp. 1726–1732, 2007. View at Publisher · View at Google Scholar · View at Scopus
  204. T. Zhang, J. Lou, R. Zhong et al., “Genetic variants in the folate pathway and the risk of neural tube defects: a meta-analysis of the published literature,” PLoS ONE, vol. 8, no. 4, Article ID e59570, 2013. View at Publisher · View at Google Scholar · View at Scopus
  205. H. J. Blom, G. M. Shaw, M. Den Heijer, and R. H. Finnell, “Neural tube defects and folate: case far from closed,” Nature Reviews Neuroscience, vol. 7, no. 9, pp. 724–731, 2006. View at Publisher · View at Google Scholar · View at Scopus
  206. N. Safra, A. G. Bassuk, P. J. Ferguson et al., “Genome-wide association mapping in dogs enables identification of the homeobox gene, NKX2-8, as a genetic component of neural tube defects in humans,” PLoS Genetics, vol. 9, no. 7, Article ID e1003646, 2013. View at Publisher · View at Google Scholar · View at Scopus
  207. A. G. Bassuk, L. B. Muthuswamy, R. Boland et al., “Copy number variation analysis implicates the cell polarity gene glypican 5 as a human spina bifida candidate gene,” Human Molecular Genetics, vol. 22, no. 6, pp. 1097–1111, 2013. View at Publisher · View at Google Scholar · View at Scopus
  208. Y. Gao, X. Chen, S. Shangguan et al., “Association study of PARD3 gene polymorphisms with neural tube defects in a Chinese han population,” Reproductive Sciences, vol. 19, no. 7, pp. 764–771, 2012. View at Publisher · View at Google Scholar · View at Scopus
  209. L. Gonzalez-Herrera, R. Martín Cerda-Flores, M. Luna-Rivero et al., “Paraoxonase 1 polymorphisms and haplotypes and the risk for having offspring affected with spina bifida in Southeast Mexico,” Birth Defects Research A—Clinical and Molecular Teratology, vol. 88, no. 11, pp. 987–994, 2010. View at Publisher · View at Google Scholar · View at Scopus
  210. J. Liu, L. Wang, Y. Fu et al., “Association between maternal COMT gene polymorphisms and fetal neural tube defects risk in a Chinese population,” Birth Defects Research A—Clinical and Molecular Teratology, vol. 100, no. 1, pp. 22–29, 2014. View at Publisher · View at Google Scholar · View at Scopus
  211. A. Narisawa, S. Komatsuzaki, A. Kikuchi et al., “Mutations in genes encoding the glycine cleavage system predispose to neural tube defects in mice and humans,” Human Molecular Genetics, vol. 21, no. 7, pp. 1496–1503, 2012. View at Publisher · View at Google Scholar · View at Scopus
  212. D. R. Krupp, K. L. Soldano, M. E. Garrett, H. Cope, A. E. Ashley-Koch, and S. G. Gregory, “Missing genetic risk in neural tube defects: can exome sequencing yield an insight?” Birth Defects Research A—Clinical and Molecular Teratology, vol. 100, no. 8, pp. 642–646, 2014. View at Publisher · View at Google Scholar · View at Scopus
  213. S. F. Gilbert, Developmental Biology, Sinauer Associates, Baltimore, Md, USA, 2003.
  214. R. Keller, “Cell migration during gastrulation,” Current Opinion in Cell Biology, vol. 17, no. 5, pp. 533–541, 2005. View at Publisher · View at Google Scholar · View at Scopus
  215. A. J. Copp, N. D. E. Greene, and J. N. Murdoch, “The genetic basis of mammalian neurulation,” Nature Reviews Genetics, vol. 4, no. 10, pp. 784–793, 2003. View at Publisher · View at Google Scholar · View at Scopus
  216. A. J. Copp, F. A. Brook, J. Peter Estibeiro, A. S. W. Shum, and D. L. Cockroft, “The embryonic development of mammalian neural tube defects,” Progress in Neurobiology, vol. 35, no. 5, pp. 363–403, 1990. View at Publisher · View at Google Scholar · View at Scopus
  217. J. A. Golden and G. F. Chernoff, “Intermittent pattern of neural tube closure in two strains of mice,” Teratology, vol. 47, no. 1, pp. 73–80, 1993. View at Publisher · View at Google Scholar · View at Scopus
  218. M. I. Van Allen, D. K. Kalousek, G. F. Chernoff et al., “Evidence for multi-site closure of the neural tube in humans,” American Journal of Medical Genetics, vol. 47, no. 5, pp. 723–743, 1993. View at Publisher · View at Google Scholar · View at Scopus
  219. R. O'Rahilly and F. Müller, “The two sites of fusion of the neural folds and the two neuropores in the human embryo,” Teratology, vol. 65, no. 4, pp. 162–170, 2002. View at Publisher · View at Google Scholar · View at Scopus
  220. A. J. Copp and M. Bernfield, “Etiology and pathogenesis of human neural tube defects: insights from mouse models,” Current Opinion in Pediatrics, vol. 6, no. 6, pp. 624–631, 1994. View at Publisher · View at Google Scholar · View at Scopus
  221. L. A. Davidson and R. E. Keller, “Neural tube closure in Xenopus laevis involves medial migration, directed protrusive activity, cell intercalation and convergent extension,” Development, vol. 126, no. 20, pp. 4547–4556, 1999. View at Google Scholar · View at Scopus
  222. H. W. M. Van Straaten, T. Jaskoll, A. M. J. Rousseau et al., “Raphe of the posterior neural tube in the chick embryo: its closure and reopening as studied in living embryos with a high definition light microscope,” Developmental Dynamics, vol. 198, no. 1, pp. 65–76, 1993. View at Publisher · View at Google Scholar · View at Scopus
  223. J.-F. Colas and G. C. Schoenwolf, “Subtractive hybridization identifies chick-cripto, a novel EGF-CFC ortholog expressed during gastrulation, neurulation and early cardiogenesis,” Gene, vol. 255, no. 2, pp. 205–217, 2000. View at Publisher · View at Google Scholar · View at Scopus
  224. A. J. Copp and N. D. E. Greene, “Defining a PARticular pathway of neural tube closure,” Developmental Cell, vol. 18, no. 1, pp. 1–2, 2010. View at Publisher · View at Google Scholar · View at Scopus
  225. P. Ybot-Gonzalez, D. Savery, D. Gerrelli et al., “Convergent extension, planar-cell-polarity signalling and initiation of mouse neural tube closure,” Development, vol. 134, no. 4, pp. 789–799, 2007. View at Publisher · View at Google Scholar · View at Scopus
  226. J.-F. Colas and G. C. Schoenwolf, “Towards a cellular and molecular understanding of neurulation,” Developmental Dynamics, vol. 221, no. 2, pp. 117–145, 2001. View at Publisher · View at Google Scholar · View at Scopus
  227. J. B. Wallingford, S. E. Fraser, and R. M. Harland, “Convergent extension: the molecular control of polarized cell movement during embryonic development,” Developmental Cell, vol. 2, no. 6, pp. 695–706, 2002. View at Publisher · View at Google Scholar · View at Scopus
  228. Y. Yamaguchi, N. Shinotsuka, K. Nonomura et al., “Live imaging of apoptosis in a novel transgenic mouse highlights its role in neural tube closure,” Journal of Cell Biology, vol. 195, no. 6, pp. 1047–1060, 2011. View at Publisher · View at Google Scholar · View at Scopus
  229. I. E. Zohn, C. R. Chesnutt, and L. Niswander, “Cell polarity pathways converge and extend to regulate neural tube closure,” Trends in Cell Biology, vol. 13, no. 9, pp. 451–454, 2003. View at Publisher · View at Google Scholar · View at Scopus
  230. Y. Komiya and R. Habas, “Wnt signal transduction pathways,” Organogenesis, vol. 4, no. 2, pp. 68–75, 2008. View at Publisher · View at Google Scholar · View at Scopus
  231. J. L. Smith and G. C. Schoenwolf, “Further evidence of extrinsic forces in bending of the neural plate,” Journal of Comparative Neurology, vol. 307, no. 2, pp. 225–236, 1991. View at Publisher · View at Google Scholar · View at Scopus
  232. A. S. W. Shum and A. J. Copp, “Regional differences in morphogenesis of the neuroepithelium suggest multiple mechanisms of spinal neurulation in the mouse,” Anatomy and Embryology, vol. 194, no. 1, pp. 65–73, 1996. View at Google Scholar · View at Scopus
  233. D. Moran and R. W. Rice, “An ultrastructural examination of the role of cell membrane surface coat material during neurulation,” Journal of Cell Biology, vol. 64, no. 1, pp. 172–181, 1975. View at Publisher · View at Google Scholar · View at Scopus
  234. R. E. Waterman, “SEM observations of surface alterations associated with neural tube closure in the mouse and hamster,” Anatomical Record, vol. 183, no. 1, pp. 95–98, 1975. View at Publisher · View at Google Scholar · View at Scopus
  235. R. E. Waterman, “Topographical changes along the neural fold associated with neurulation in the hamster and mouse,” American Journal of Anatomy, vol. 146, no. 2, pp. 151–171, 1976. View at Publisher · View at Google Scholar · View at Scopus
  236. R. W. Rice and D. J. Moran, “A scanning electron microscopic and x-ray microanalytic study of cell surface material during amphibian neurulation,” Journal of Experimental Zoology, vol. 201, no. 3, pp. 471–478, 1977. View at Publisher · View at Google Scholar · View at Scopus
  237. L. L. Mak, “Ultrastructural studies of amphibian neural fold fusion,” Developmental Biology, vol. 65, no. 2, pp. 435–446, 1978. View at Publisher · View at Google Scholar · View at Scopus
  238. T. W. Sadler, “Distribution of surface coat material on fusing neural folds of mouse embryos during neurulation,” Anatomical Record, vol. 191, no. 3, pp. 345–349, 1978. View at Publisher · View at Google Scholar · View at Scopus
  239. J. A. G. Geelen and J. Langman, “Ultrastructural observations on closure of the neural tube in the mouse,” Anatomy and Embryology, vol. 156, no. 1, pp. 73–88, 1979. View at Publisher · View at Google Scholar · View at Scopus
  240. A. Smits-Van Prooije, R. Poelmann, J. Dubbeldam, M. Mentink, and C. Vermeij-Keers, “The formation of the neural tube in rat embryos, cultured in vitro, studied with teratogens,” Acta Histochemica. Supplement, vol. 32, pp. 41–45, 1986. View at Google Scholar
  241. H. Takahashi and R. I. Howes, “Binding pattern of ferritin-labeled lectins (RCAI and WGA) during neural tube closure in the bantam embryo,” Anatomy and Embryology, vol. 174, no. 3, pp. 283–288, 1986. View at Publisher · View at Google Scholar · View at Scopus
  242. H. Takahashi, “Changes in peanut lectin binding sites on the neuroectoderm during neural tube formation in the bantam chick embryo,” Anatomy and Embryology, vol. 178, no. 4, pp. 353–358, 1988. View at Publisher · View at Google Scholar · View at Scopus
  243. J. Holmberg, D. L. Clarke, and J. Frisen, “Regulation of repulsion versus adhesion by different splice forms of an Eph receptor,” Nature, vol. 408, no. 6809, pp. 203–206, 2000. View at Publisher · View at Google Scholar · View at Scopus
  244. N. M. Abdul-Aziz, M. Turmaine, N. D. E. Greene, and A. J. Copp, “EphrinA-EphA receptor interactions in mouse spinal neurulation: implications for neural fold fusion,” The International Journal of Developmental Biology, vol. 53, no. 4, pp. 559–568, 2009. View at Publisher · View at Google Scholar · View at Scopus
  245. C. Pyrgaki, P. Trainor, A.-K. Hadjantonakis, and L. Niswander, “Dynamic imaging of mammalian neural tube closure,” Developmental Biology, vol. 344, no. 2, pp. 941–947, 2010. View at Publisher · View at Google Scholar · View at Scopus
  246. M. J. Harris and D. M. Juriloff, “Mini-review: toward understanding mechanisms of genetic neural tube defects in mice,” Teratology, vol. 60, no. 5, pp. 292–305, 1999. View at Publisher · View at Google Scholar · View at Scopus
  247. A. Dady, E. Havis, V. Escriou, M. Catala, and J.-L. Duband, “Junctional neurulation: a unique developmental program shaping a discrete region of the spinal cord highly susceptible to neural tube defects,” Journal of Neuroscience, vol. 34, no. 39, pp. 13208–13221, 2014. View at Publisher · View at Google Scholar · View at Scopus
  248. L. S. Segal, W. Czoch, W. L. Hennrikus, M. Wade Shrader, and P. M. Kanev, “The spectrum of musculoskeletal problems in lipomyelomeningocele,” Journal of Children's Orthopaedics, vol. 7, no. 6, pp. 513–519, 2013. View at Publisher · View at Google Scholar · View at Scopus
  249. M. Montcouquiol, E. B. Crenshaw III, and M. W. Kelley, “Noncanonical Wnt signaling and neural polarity,” Annual Review of Neuroscience, vol. 29, pp. 363–386, 2006. View at Publisher · View at Google Scholar · View at Scopus
  250. J. B. Wallingford and R. Habas, “The developmental biology of Dishevelled: an enigmatic protein governing cell fate and cell polarity,” Development, vol. 132, no. 20, pp. 4421–4436, 2005. View at Publisher · View at Google Scholar · View at Scopus
  251. P. Ybot-Gonzalez, C. Gaston-Massuet, G. Girdler et al., “Neural plate morhogenesis during mouse neurulation is regulated by antagonism of Bmp signalling,” Development, vol. 134, no. 17, pp. 3203–3211, 2007. View at Publisher · View at Google Scholar · View at Scopus
  252. Y. Yamaguchi and M. Miura, “How to form and close the brain: insight into the mechanism of cranial neural tube closure in mammals,” Cellular and Molecular Life Sciences, vol. 70, no. 17, pp. 3171–3186, 2013. View at Publisher · View at Google Scholar · View at Scopus
  253. S. L. McDonald and A. Silver, “The opposing roles of Wnt-5a in cancer,” British Journal of Cancer, vol. 101, no. 2, pp. 209–214, 2009. View at Publisher · View at Google Scholar · View at Scopus
  254. R. Keller, “Shaping the vertebrate body plan by polarized embryonic cell movements,” Science, vol. 298, no. 5600, pp. 1950–1954, 2002. View at Publisher · View at Google Scholar · View at Scopus
  255. A. Dabdoub, M. J. Donohue, A. Brennan et al., “Wnt signaling mediates reorientation of outer hair cell stereociliary bundles in the mammalian cochlea,” Development, vol. 130, no. 11, pp. 2375–2384, 2003. View at Publisher · View at Google Scholar · View at Scopus
  256. L. V. Goodrich and D. Strutt, “Principles of planar polarity in animal development,” Development, vol. 138, no. 10, pp. 1877–1892, 2011. View at Publisher · View at Google Scholar · View at Scopus
  257. J. Shih and R. Keller, “Cell motility driving mediolateral intercalation in explants of Xenopus laevis,” Development, vol. 116, no. 4, pp. 901–914, 1992. View at Google Scholar · View at Scopus
  258. L. A. Lowery and H. Sive, “Strategies of vertebrate neurulation and a re-evaluation of teleost neural tube formation,” Mechanisms of Development, vol. 121, no. 10, pp. 1189–1197, 2004. View at Publisher · View at Google Scholar · View at Scopus
  259. M. J. Harrington, E. Hong, and R. Brewster, “Comparative analysis of neurulation: first impressions do not count,” Molecular Reproduction and Development, vol. 76, no. 10, pp. 954–965, 2009. View at Publisher · View at Google Scholar · View at Scopus
  260. T. J. Klein and M. Mlodzik, “Planar cell polarization: an emerging model points in the right direction,” Annual Review of Cell and Developmental Biology, vol. 21, pp. 155–176, 2005. View at Publisher · View at Google Scholar · View at Scopus
  261. H. Matakatsu and S. S. Blair, “Interactions between Fat and Dachsous and the regulation of planar cell polarity in the Drosophila wing,” Development, vol. 131, no. 15, pp. 3785–3794, 2004. View at Publisher · View at Google Scholar · View at Scopus
  262. J. Casal, P. A. Lawrence, and G. Struhl, “Two separate molecular systems, Dachsous/Fat and Starry night/Frizzled, act independently to confer planar cell polarity,” Development, vol. 133, no. 22, pp. 4561–4572, 2006. View at Publisher · View at Google Scholar · View at Scopus
  263. E. K. Vladar, D. Antic, and J. D. Axelrod, “Planar cell polarity signaling: the developing cell's compass,” Cold Spring Harbor Perspectives in Biology, vol. 1, no. 3, Article ID a002964, 2009. View at Publisher · View at Google Scholar · View at Scopus
  264. M. Matis and J. D. Axelrod, “Regulation of PCP by the fat signaling pathway,” Genes and Development, vol. 27, no. 20, pp. 2207–2220, 2013. View at Publisher · View at Google Scholar · View at Scopus
  265. D. Gubb and A. García-Bellido, “A genetic analysis of the determination of cuticular polarity during development in Drosophila melanogaster,” Journal of Embryology and Experimental Morphology, vol. 68, pp. 37–57, 1982. View at Google Scholar · View at Scopus
  266. P. N. Adler, J. Taylor, and J. Charlton, “The domineering non-autonomy of frizzled and Van Gogh clones in the Drosophila wing is a consequence of a disruption in local signaling,” Mechanisms of Development, vol. 96, no. 2, pp. 197–207, 2000. View at Publisher · View at Google Scholar · View at Scopus
  267. L. L. Wong and P. N. Adler, “Tissue polarity genes of Drosophila regulate the subcellular location for prehair initiation in pupal wing cells,” Journal of Cell Biology, vol. 123, no. 1, pp. 209–221, 1993. View at Publisher · View at Google Scholar · View at Scopus
  268. J. N. Murdoch, K. Doudney, C. Paternotte, A. J. Copp, and P. Stanier, “Severe neural tube defects in the loop-tail mouse result from mutation of Lpp1, a novel gene involved in floor plate specification,” Human Molecular Genetics, vol. 10, no. 22, pp. 2593–2601, 2001. View at Publisher · View at Google Scholar · View at Scopus
  269. J. Wang, N. S. Hamblet, S. Mark et al., “Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation,” Development, vol. 133, no. 9, pp. 1767–1778, 2006. View at Publisher · View at Google Scholar · View at Scopus
  270. J. A. Curtin, E. Quint, V. Tsipouri et al., “Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse,” Current Biology, vol. 13, no. 13, pp. 1129–1133, 2003. View at Publisher · View at Google Scholar · View at Scopus
  271. N. S. Hamblet, N. Lijam, P. Ruiz-Lozano et al., “Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure,” Development, vol. 129, no. 24, pp. 5827–5838, 2002. View at Publisher · View at Google Scholar · View at Scopus
  272. S. L. Etheridge, S. Ray, S. Li et al., “Murine dishevelled 3 functions in redundant pathways with dishevelled 1 and 2 in normal cardiac outflow tract, cochlea, and neural tube development,” PLoS Genetics, vol. 4, no. 11, Article ID e1000259, 2008. View at Publisher · View at Google Scholar · View at Scopus
  273. Y. Wang, N. Guo, and J. Nathans, “The role of Frizzled3 and Frizzled6 in neural tube closure and in the planar polarity of inner-ear sensory hair cells,” Journal of Neuroscience, vol. 26, no. 8, pp. 2147–2156, 2006. View at Publisher · View at Google Scholar · View at Scopus
  274. E. Torban, A.-M. Patenaude, S. Leclerc et al., “Genetic interaction between members of the Vangl family causes neural tube defects in mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 9, pp. 3449–3454, 2008. View at Publisher · View at Google Scholar · View at Scopus
  275. X. Lu, A. G. M. Borchers, C. Jolicoeur, H. Rayburn, J. C. Baker, and M. Tessier-Lavigne, “PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates,” Nature, vol. 430, no. 6995, pp. 93–98, 2004. View at Publisher · View at Google Scholar · View at Scopus
  276. J. N. Murdoch, D. J. Henderson, K. Doudney et al., “Disruption of scribble (Scrb1) causes severe neural tube defects in the circletail mouse,” Human Molecular Genetics, vol. 12, no. 2, pp. 87–98, 2003. View at Publisher · View at Google Scholar · View at Scopus
  277. R. Suriben, S. Kivimäe, D. A. C. Fisher, R. T. Moon, and B. N. R. Cheyette, “Posterior malformations in Dact1 mutant mice arise through misregulated Vangl2 at the primitive streak,” Nature Genetics, vol. 41, no. 9, pp. 977–985, 2009. View at Publisher · View at Google Scholar · View at Scopus
  278. M. Placzek, T. Yamada, M. Tessier-Lavigne, T. Jessell, and J. Dodd, “Control of dorsoventral pattern in vertebrate neural development: induction and polarizing properties of the floor plate,” Development, vol. 113, no. 2, pp. 105–122, 1991. View at Google Scholar · View at Scopus
  279. M. Placzek, M. Tessier-Lavigne, T. Yamada, T. Jessell, and J. Dodd, “Mesodermal control of neural cell identity: floor plate induction by the notochord,” Science, vol. 250, no. 4983, pp. 985–988, 1990. View at Publisher · View at Google Scholar · View at Scopus
  280. T. Yamada, M. Placzek, H. Tanaka, J. Dodd, and T. M. Jessell, “Control of cell pattern in the developing nervous system: polarizing activity of the floor plate and notochord,” Cell, vol. 64, no. 3, pp. 635–647, 1991. View at Publisher · View at Google Scholar · View at Scopus
  281. T. Yamada, S. L. Pfaff, T. Edlund, and T. M. Jessell, “Control of cell pattern in the neural tube: motor neuron induction by diffusible factors from notochord and floor plate,” Cell, vol. 73, no. 4, pp. 673–686, 1993. View at Publisher · View at Google Scholar · View at Scopus
  282. M. D. Goulding, A. Lumsden, and P. Gruss, “Signals from the notochord and floor plate regulate the region-specific expression of two Pax genes in the developing spinal cord,” Development, vol. 117, no. 3, pp. 1001–1016, 1993. View at Google Scholar · View at Scopus
  283. D. S. Eom, S. Amarnath, J. L. Fogel, and S. Agarwala, “Bone morphogenetic proteins regulate hinge point formation during neural tube closure by dynamic modulation of apicobasal polarity,” Birth Defects Research Part A: Clinical and Molecular Teratology, vol. 94, no. 10, pp. 804–816, 2012. View at Publisher · View at Google Scholar · View at Scopus
  284. H. W. M. van Straaten, J. W. M. Hekking, E. J. L. M. Wiertz-Hoessels, F. Thors, and J. Drukker, “Effect of the notochord on the differentiation of a floor plate area in the neural tube of the chick embryo,” Anatomy and Embryology, vol. 177, no. 4, pp. 317–324, 1988. View at Publisher · View at Google Scholar · View at Scopus
  285. H. W. M. van Straaten, J. W. M. Hekking, F. Thors, E. L. Wiertz-Hoessels, and J. Drukker, “Induction of an additional floor plate in the neural tube,” Acta Morphologica Neerlando-Scandinavica, vol. 23, no. 2, pp. 91–97, 1985. View at Google Scholar · View at Scopus
  286. J. L. Smith and G. C. Schoenwolf, “Notochordal induction of cell wedging in the chick neural plate and its role in neural tube formation,” Journal of Experimental Zoology, vol. 250, no. 1, pp. 49–62, 1989. View at Publisher · View at Google Scholar · View at Scopus
  287. P. Ybot-Gonzalez, P. Cogram, D. Gerrelli, and A. J. Copp, “Sonic hedgehog and the molecular regulation of mouse neural tube closure,” Development, vol. 129, no. 10, pp. 2507–2517, 2002. View at Google Scholar · View at Scopus
  288. K. F. Liem Jr., T. M. Jessell, and J. Briscoe, “Regulation of the neural patterning activity of sonic hedgehog by secreted BMP inhibitors expressed by notochord and somites,” Development, vol. 127, no. 22, pp. 4855–4866, 2000. View at Google Scholar · View at Scopus
  289. N. D. E. Greene and A. J. Copp, “Development of the vertebrate central nervous system: formation of the neural tube,” Prenatal Diagnosis, vol. 29, no. 4, pp. 303–311, 2009. View at Publisher · View at Google Scholar · View at Scopus
  290. S. G. McShane, M. A. Molè, D. Savery, N. D. E. Greene, P. P. L. Tam, and A. J. Copp, “Cellular basis of neuroepithelial bending during mouse spinal neural tube closure,” Developmental Biology, vol. 404, no. 2, pp. 113–124, 2015. View at Publisher · View at Google Scholar · View at Scopus
  291. P. Ybot-Gonzalez, C. Gaston-Massuet, G. Girdler et al., “Neural plate morphogenesis during mouse neurulation is regulated by antagonism of Bmp signalling,” Development, vol. 134, no. 17, pp. 3203–3211, 2007. View at Publisher · View at Google Scholar · View at Scopus
  292. J. A. McMahon, S. Takada, L. B. Zimmerman, C.-M. Fan, R. M. Harland, and A. P. McMahon, “Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite,” Genes & Development, vol. 12, no. 10, pp. 1438–1452, 1998. View at Publisher · View at Google Scholar · View at Scopus
  293. R. W. Stottmann, M. Berrong, K. Matta, M. Choi, and J. Klingensmith, “The BMP antagonist Noggin promotes cranial and spinal neurulation by distinct mechanisms,” Developmental Biology, vol. 295, no. 2, pp. 647–663, 2006. View at Publisher · View at Google Scholar · View at Scopus
  294. J. Groppe, J. Greenwald, E. Wiater et al., “Structural basis of BMP signalling inhibition by the cystine knot protein Noggin,” Nature, vol. 420, no. 6916, pp. 636–642, 2002. View at Publisher · View at Google Scholar · View at Scopus
  295. L. J. Brunet, J. A. McMahon, A. P. McMahon, and R. M. Harland, “Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton,” Science, vol. 280, no. 5368, pp. 1455–1457, 1998. View at Publisher · View at Google Scholar · View at Scopus
  296. J. Laurikkala, Y. Kassai, L. Pakkasjärvi, I. Thesleff, and N. Itoh, “Identification of a secreted BMP antagonist, ectodin, integrating BMP, FGF, and SHH signals from the tooth enamel knot,” Developmental Biology, vol. 264, no. 1, pp. 91–105, 2003. View at Publisher · View at Google Scholar · View at Scopus
  297. G. W. Yip, P. Ferretti, and A. J. Copp, “Heparan sulphate proteoglycans and spinal neurulation in the mouse embryo,” Development, vol. 129, no. 9, pp. 2109–2119, 2002. View at Google Scholar · View at Scopus
  298. B. Ciruna and J. Rossant, “FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak,” Developmental Cell, vol. 1, no. 1, pp. 37–49, 2001. View at Publisher · View at Google Scholar · View at Scopus
  299. S. Takada, K. L. Stark, M. J. Shea, G. Vassileva, J. A. McMahon, and A. P. McMahon, “Wnt-3a regulates somite and tailbud formation in the mouse embryo,” Genes and Development, vol. 8, no. 2, pp. 174–189, 1994. View at Publisher · View at Google Scholar · View at Scopus
  300. K. Niederreither, V. Subbarayan, P. Dollé, and P. Chambon, “Embryonic retinoic acid synthesis is essential for early mouse post-implantation development,” Nature Genetics, vol. 21, no. 4, pp. 444–448, 1999. View at Publisher · View at Google Scholar · View at Scopus
  301. C. F. Hung, H. K. Hsu, and K. R. Lin, “SEM observations of the neural fold associated with neurulation in the rat,” Proceedings of the National Science Council, Republic of China, Part B: Life Sciences, vol. 10, no. 4, pp. 287–290, 1986. View at Google Scholar · View at Scopus
  302. A. Lawson and M. A. England, “Neural fold fusion in the cranial region of the chick embryo,” Developmental Dynamics, vol. 212, no. 4, pp. 473–481, 1998. View at Publisher · View at Google Scholar · View at Scopus
  303. H. W. M. Van Straaten, M. C. E. Peeters, K. F. W. Szpak, and J. W. M. Hekking, “Initial closure of the mesencephalic neural groove in the chick embryo involves a releasing zipping-up mechanism,” Developmental Dynamics, vol. 209, no. 4, pp. 333–341, 1997. View at Publisher · View at Google Scholar · View at Scopus
  304. B. Ciruna, A. Jenny, D. Lee, M. Mlodzik, and A. F. Schier, “Planar cell polarity signalling couples cell division and morphogenesis during neurulation,” Nature, vol. 439, no. 7073, pp. 220–224, 2006. View at Publisher · View at Google Scholar · View at Scopus
  305. D. Rashid, K. Newell, L. Shama, and R. Bradley, “A requirement for NF-protocadherin and TAF1/Set in cell adhesion and neural tube formation,” Developmental Biology, vol. 291, no. 1, pp. 170–181, 2006. View at Publisher · View at Google Scholar · View at Scopus
  306. L. A. Davidson, A. M. Ezin, and R. Keller, “Embryonic wound healing by apical contraction and ingression in Xenopus laevis,” Cell Motility and the Cytoskeleton, vol. 53, no. 3, pp. 163–176, 2002. View at Publisher · View at Google Scholar · View at Scopus
  307. M. R. Brouns, S. F. Matheson, K.-Q. Hu et al., “The adhesion signaling molecule p190 RhoGAP is required for morphogenetic processes in neural development,” Development, vol. 127, no. 22, pp. 4891–4903, 2000. View at Google Scholar · View at Scopus
  308. I. de Diego, K. Kyriakopoulou, D. Karagogeos, and M. Wassef, “Multiple influences on the migration of precerebellar neurons in the caudal medulla,” Development, vol. 129, no. 2, pp. 297–306, 2002. View at Google Scholar · View at Scopus
  309. R. Keller, “Mechanisms of elongation in embryogenesis,” Development, vol. 133, no. 12, pp. 2291–2302, 2006. View at Publisher · View at Google Scholar · View at Scopus
  310. D. A. Hackett, J. L. Smith, and G. C. Schoenwolf, “Epidermal ectoderm is required for full elevation and for convergence during bending of the avian neural plate,” Developmental Dynamics, vol. 210, no. 4, pp. 397–406, 1997. View at Publisher · View at Google Scholar · View at Scopus
  311. S. L. Haigo, J. D. Hildebrand, R. M. Harland, and J. B. Wallingford, “Shroom induces apical constriction and is required for hingepoint formation during neural tube closure,” Current Biology, vol. 13, no. 24, pp. 2125–2137, 2003. View at Publisher · View at Google Scholar · View at Scopus
  312. M. Bailly, “Connecting cell adhesion to the actin polymerization machinery: vinculin as the missing link?” Trends in Cell Biology, vol. 13, no. 4, pp. 163–165, 2003. View at Publisher · View at Google Scholar · View at Scopus
  313. E. Andersson, L. Bryjova, K. Biris, T. P. Yamaguchi, E. Arenas, and V. Bryja, “Genetic interaction between Lrp6 and Wnt5a during mouse development,” Developmental Dynamics, vol. 239, no. 1, pp. 237–245, 2010. View at Publisher · View at Google Scholar · View at Scopus
  314. X. Miró, X. Zhou, S. Boretius et al., “Haploinsufficiency of the murine polycomb gene Suz12 results in diverse malformations of the brain and neural tube,” Disease Models and Mechanisms, vol. 2, no. 7-8, pp. 412–418, 2009. View at Publisher · View at Google Scholar · View at Scopus
  315. P. Magnaghi, C. Roberts, S. Lorain, M. Lipinski, and P. J. Scambler, “HIRA, a mammalian homologue of saccharomyces cerevisiae transcriptional co-repressors, interacts with Pax3,” Nature Genetics, vol. 20, no. 1, pp. 74–77, 1998. View at Publisher · View at Google Scholar · View at Scopus
  316. M. K. Pirity, W.-L. Wang, L. V. Wolf, E. R. Tamm, N. Schreiber-Agus, and A. Cvekl, “Rybp, a polycomb complex-associated protein, is required for mouse eye development,” BMC Developmental Biology, vol. 7, article 39, 2007. View at Publisher · View at Google Scholar · View at Scopus
  317. K. Fujii, “Primary cilia and hedgehog signaling,” No To Hattatsu, vol. 47, pp. 259–265, 2015. View at Google Scholar
  318. C. Goumy, M. Gay-Bellile, E. Eymard-Pierre et al., “De novo 2q36.1q36.3 interstitial deletion involving the PAX3 and EPHA4 genes in a fetus with spina bifida and cleft palate,” Birth Defects Research Part A: Clinical and Molecular Teratology, vol. 100, no. 6, pp. 507–511, 2014. View at Publisher · View at Google Scholar · View at Scopus
  319. F. R. Schubert, P. Tremblay, A. Mansouri et al., “Early mesodermal phenotypes in Splotch suggest a role for Pax3 in the formation of epithelial somites,” Developmental Dynamics, vol. 222, no. 3, pp. 506–521, 2001. View at Publisher · View at Google Scholar · View at Scopus
  320. H. Roudgari, P. A. Farndon, A. D. Murray, C. Hardy, and Z. Miedzybrodzka, “Is PATCHED an important candidate gene for neural tube defects? Cranial and thoracic neural tube defects in a family with Gorlin syndrome: a case report,” Clinical Genetics, vol. 82, no. 1, pp. 71–76, 2012. View at Publisher · View at Google Scholar · View at Scopus
  321. J. Luo, N. Balkin, J. F. Stewart, J. F. Sarwark, J. Charrow, and J. S. Nye, “Neural tube defects and the 13q deletion syndrome: evidence for a critical region in 13q33-34,” American Journal of Medical Genetics Part A, vol. 91, no. 3, pp. 227–230, 2000. View at Publisher · View at Google Scholar · View at Scopus
  322. L. Rodríguez, I. C. Pérez, J. H. Montes, M. L. L. Jareño, F. L. Grondona, and M. L. Martínez-Frías, “Terminal deletion of the chromosome 7(q36-qter) in an infant with sacral agenesis and anterior myelomeningocele,” American Journal of Medical Genetics, vol. 110, no. 1, pp. 73–77, 2002. View at Publisher · View at Google Scholar · View at Scopus