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Review
. 2013 Aug;12(8):799-810.
doi: 10.1016/S1474-4422(13)70110-8. Epub 2013 Jun 19.

Neural tube defects: recent advances, unsolved questions, and controversies

Andrew J Copp  1 , Philip Stanier, Nicholas D E Greene
Affiliations
Review

Neural tube defects: recent advances, unsolved questions, and controversies

Andrew J Copp et al. Lancet Neurol. 2013 Aug.

Abstract

Neural tube defects are severe congenital malformations affecting around one in every 1000 pregnancies. An innovation in clinical management has come from the finding that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention with folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in the UK. Genetic predisposition accounts for most of the risk of neural tube defects, and genes that regulate folate one-carbon metabolism and planar cell polarity have been strongly implicated. The sequence of human neural tube closure events remains controversial, but studies of mouse models of neural tube defects show that anencephaly, open spina bifida, and craniorachischisis result from failure of primary neurulation, whereas skin-covered spinal dysraphism results from defective secondary neurulation. Other malformations, such as encephalocele, are likely to be postneurulation disorders.

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Figures

Figure 1
Figure 1. Summary of folate one-carbon metabolism showing the main pathways and reactions.
Blue shading: processing of folates in the digestive tract, transport and cellular retention (by addition of glutamates). Yellow shading: transfer of one-carbon groups between folate molecules for purine and pyrimidine biosynthesis. Pink shading: reactions of the methylation cycle that generate SAM, the universal methyl group donor. Green: mitochondrial reactions that generate formate via cleavage of glycine. Enzymes whose genetic variation have been implicated in human NTDs are indicated in black boxes. Figure modified from Greene et al, 2009 .
Figure 2
Figure 2. Summary of non-canonical Wnt signalling in a mammalian cell.
Black arrows indicate the signalling pathway necessary for establishment of planar cell polarity (PCP). Known biochemical interactions are indicated by blue arrows and genetic interactions are shown by red arrows. Genes that have been implicated in human NTDs are indicated by asterisks. Figure modified from Greene et al, 2009 .
Figure 3
Figure 3. Schematic showing different concepts of how mouse (A) and human (B-D) embryos undergo primary neurulation.
The site of secondary neurulation in the tailbud is indicated by green shading. (A) Pattern of mouse neural tube closure, as experimentally verified in multiple mouse strains . (B) The original concept of human closure in which bidirectional zippering occurs from an initiation site (Closure 1) towards the rostral and caudal extremities. (C) Modified concept based on mouse multi-site closure, as used for retrospective interpretation of human NTDs . (D) Pattern of human neural tube closure based on embryo observation .
Figure 4
Figure 4. Sites of origin of NTDs in the human embryo directly resulting from disturbance of primary or secondary neurulation
(A) Anencephaly is the consequence of faulty cranial closure events; (B) Craniorachischisis arises when Closure 1 fails; (C) Open spina bifida results from failure of caudal neuropore closure; (D) Skin-covered spinal ‘dysraphism’ arises through disturbance of the secondary neurulation process. Figure modified from: Copp, 2005. In: R. A. Meyers (Ed.), Encyclopedia of Molecular Cell Biology and Molecular Medicine, 9, 119-138. Wiley-VCH, Weinheim (B,C); Copp, 2008. In: eLS. John Wiley & Sons Ltd, A20913, Chichester. http://www.els.net (D).
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References

    1. Mitchell LE. Epidemiology of neural tube defects. Am J Med Genet C Semin Med Genet. 2005;135:88–94. - PubMed
    1. Creasy MR, Alberman ED. Congenital malformations of the central nervous system in spontaneous abortions. J Med Genet. 1976;13:9–16. - PMC - PubMed
    1. Dolk H, Loane M, Garne E. The prevalence of congenital anomalies in Europe. Adv Exp Med Biol. 2010;686:349–64. - PubMed
    1. Obladen M. Cats, frogs, and snakes: early concepts of neural tube defects. J Child Neurol. 2011;26:1452–61. - PubMed
    1. Record RG, McKeown T. Congenital malformations of the central nervous system. I. A survey of 930 cases. Brit J Soc Med. 1949;3:183–219.

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