{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:10:06Z","timestamp":1791144606907,"version":"4.1.0"},"reference-count":76,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,5,29]],"date-time":"2012-05-29T00:00:00Z","timestamp":1338249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["WIREs Developmental Biology"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Neural tube defects (NTDs) are severe congenital malformations affecting 1 in every 1000 pregnancies.\n                    <jats:italic>\u2018Open\u2019 NTDs<\/jats:italic>\n                    result from failure of primary neurulation as seen in anencephaly, myelomeningocele (open spina bifida), and craniorachischisis. Degeneration of the persistently open neural tube\n                    <jats:italic>in utero<\/jats:italic>\n                    leads to loss of neurological function below the lesion level.\n                    <jats:italic>\u2018Closed\u2019 NTDs<\/jats:italic>\n                    are skin\u2010covered disorders of spinal cord structure, ranging from asymptomatic spina bifida occulta to severe spinal cord tethering, and usually traceable to disruption of secondary neurulation.\n                    <jats:italic>\u2018Herniation\u2019 NTDs<\/jats:italic>\n                    are those in which meninges, with or without brain or spinal cord tissue, become exteriorized through a pathological opening in the skull or vertebral column (e.g., encephalocele and meningocele). NTDs have multifactorial etiology, with genes and environmental factors interacting to determine individual risk of malformation. While over 200 mutant genes cause open NTDs in mice, much less is known about the genetic causation of human NTDs. Recent evidence has implicated genes of the planar cell polarity signaling pathway in a proportion of cases. The embryonic development of NTDs is complex, with diverse cellular and molecular mechanisms operating at different levels of the body axis. Molecular regulatory events include the bone morphogenetic protein and Sonic hedgehog pathways which have been implicated in control of neural plate bending. Primary prevention of NTDs has been implemented clinically following the demonstration that folic acid (FA), when taken as a periconceptional supplement, can prevent many cases. Not all NTDs respond to FA, however, and adjunct therapies are required for prevention of this FA\u2010resistant category.\n                    <jats:italic>WIREs Dev Biol<\/jats:italic>\n                    2013, 2:213\u2013227. doi: 10.1002\/wdev.71\n                  <\/jats:p>\n                  <jats:p>\n                    This article is categorized under:\n                    <jats:list list-type=\"explicit-label\">\n                      <jats:list-item>\n                        <jats:p>Signaling Pathways &gt; Global Signaling Mechanisms<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Early Embryonic Development &gt; Gastrulation and Neurulation<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Birth Defects &gt; Craniofacial and Nervous System Anomalies<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>","DOI":"10.1002\/wdev.71","type":"journal-article","created":{"date-parts":[[2012,5,29]],"date-time":"2012-05-29T10:57:43Z","timestamp":1338289063000},"page":"213-227","source":"Crossref","is-referenced-by-count":232,"title":["Neural tube defects\u2014disorders of neurulation and related embryonic processes"],"prefix":"10.1002","volume":"2","author":[{"given":"Andrew J.","family":"Copp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas D. E.","family":"Greene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,5,29]]},"reference":[{"key":"e_1_2_9_1_2_1","first-page":"15","volume-title":"Neural Tube Defects: From Origin to Treatment.","author":"Wyszynski DF","year":"2006"},{"key":"e_1_2_9_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-90-481-9485-8_20"},{"key":"e_1_2_9_2_3_2","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.89.6.887"},{"key":"e_1_2_9_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30057"},{"key":"e_1_2_9_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-198411000-00006"},{"key":"e_1_2_9_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320580406"},{"key":"e_1_2_9_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.04.020"},{"key":"e_1_2_9_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1181"},{"key":"e_1_2_9_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2005.00476.x"},{"key":"e_1_2_9_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004290100169"},{"key":"e_1_2_9_2_11_2","doi-asserted-by":"publisher","DOI":"10.3171\/spi.2003.99.2.0206"},{"key":"e_1_2_9_2_12_2","first-page":"335","volume-title":"Greenfield's Neuropathology.","author":"Harding BN","year":"2008"},{"key":"e_1_2_9_2_13_2","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s12035-010-8154-0","article-title":"Molecular genetics and pathogenic mechanisms for the severe ciliopathies: insights into neurodevelopment and pathogenesis of neural tube defects.","volume":"43","author":"Logan CV","year":"2010","journal-title":"Mol Neurobiol"},{"key":"e_1_2_9_2_14_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1998.89.2.0317"},{"key":"e_1_2_9_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.bmb.a071187"},{"key":"e_1_2_9_2_16_2","first-page":"165","volume-title":"Neural Tube Defects: From Origin to Treatment.","author":"Rampersaud E","year":"2006"},{"key":"e_1_2_9_2_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30048"},{"key":"e_1_2_9_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp347"},{"key":"e_1_2_9_2_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31812"},{"key":"e_1_2_9_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20676"},{"key":"e_1_2_9_2_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00062.2007"},{"key":"e_1_2_9_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(90)90037-H"},{"key":"e_1_2_9_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.4.575"},{"key":"e_1_2_9_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420350319"},{"key":"e_1_2_9_2_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20053"},{"key":"e_1_2_9_2_26_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S1043-4526(08)00605-0","article-title":"Maternal fumonisin exposure as a risk factor for neural tube defects.","volume":"56","author":"Gelineau\u2010van WJ","year":"2009","journal-title":"Adv Food Nutr Res"},{"key":"e_1_2_9_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn262"},{"key":"e_1_2_9_2_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2643"},{"key":"e_1_2_9_2_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20539"},{"key":"e_1_2_9_2_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199611)207:3<309::AID-AJA8>3.0.CO;2-L"},{"key":"e_1_2_9_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/tera.10007"},{"key":"e_1_2_9_2_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004290050332"},{"key":"e_1_2_9_2_33_2","first-page":"129","article-title":"Normal patterns of neural tube closure differ in the human and the mouse.","volume":"18","author":"Sulik KK","year":"1998","journal-title":"Proc Greenwood Genet Cent"},{"key":"e_1_2_9_2_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420390211"},{"key":"e_1_2_9_2_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320260325"},{"key":"e_1_2_9_2_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20333"},{"key":"e_1_2_9_2_37_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.31.5.383"},{"key":"e_1_2_9_2_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20581"},{"key":"e_1_2_9_2_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001690402"},{"key":"e_1_2_9_2_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420020410"},{"key":"e_1_2_9_2_41_2","doi-asserted-by":"crossref","first-page":"4855","DOI":"10.1242\/dev.129.20.4855","article-title":"Axial progenitors with extensive potency are localised to the mouse chordoneural hinge.","volume":"129","author":"Cambray N","year":"2002","journal-title":"Development"},{"key":"e_1_2_9_2_42_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1994.1230"},{"key":"e_1_2_9_2_43_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.008177"},{"key":"e_1_2_9_2_44_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.000380"},{"key":"e_1_2_9_2_45_2","doi-asserted-by":"publisher","DOI":"10.1088\/1478-3975\/5\/1\/015007"},{"key":"e_1_2_9_2_46_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.112933"},{"key":"e_1_2_9_2_47_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00123"},{"key":"e_1_2_9_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(98)00029-X"},{"key":"e_1_2_9_2_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20686"},{"key":"e_1_2_9_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/383407a0"},{"key":"e_1_2_9_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00385-3"},{"key":"e_1_2_9_2_52_2","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1242\/dev.129.10.2507","article-title":"Sonic hedgehog and the molecular regulation of neural tube closure.","volume":"129","author":"Ybot\u2010Gonzalez P","year":"2002","journal-title":"Development"},{"key":"e_1_2_9_2_53_2","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1242\/dev.113.2.671","article-title":"Curvature of the caudal region is responsible for failure of neural tube closure in the curly tail (ct) mouse embryo.","volume":"113","author":"Brook FA","year":"1991","journal-title":"Development"},{"key":"e_1_2_9_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm961"},{"key":"e_1_2_9_2_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm221"},{"key":"e_1_2_9_2_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr031"},{"key":"e_1_2_9_2_57_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20709"},{"key":"e_1_2_9_2_58_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7031898"},{"key":"e_1_2_9_2_59_2","first-page":"333","article-title":"The role of microfilaments in cranial neurulation in rat embryos: effects of short\u2010term exposure to cytochalasin D.","volume":"88","author":"Morriss\u2010Kay GM","year":"1985","journal-title":"J Embryol Exp Morphol"},{"key":"e_1_2_9_2_60_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199907)215:3<273::AID-AJA9>3.0.CO;2-H"},{"key":"e_1_2_9_2_61_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900333106"},{"key":"e_1_2_9_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2007.04.018"},{"key":"e_1_2_9_2_63_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1971.tb03264.x"},{"key":"e_1_2_9_2_64_2","doi-asserted-by":"publisher","DOI":"10.1002\/pd.2250"},{"key":"e_1_2_9_2_65_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1014379"},{"key":"e_1_2_9_2_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amepre.2008.07.008"},{"key":"e_1_2_9_2_67_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-011-1492-8"},{"key":"e_1_2_9_2_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(80)90886-7"},{"key":"e_1_2_9_2_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)90133-A"},{"key":"e_1_2_9_2_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68582-6"},{"key":"e_1_2_9_2_71_2","first-page":"1","article-title":"Not all cases of neural\u2010tube defect can be prevented by increasing the intake of folic acid.","volume":"16","author":"Heseker HB","year":"2008","journal-title":"Br J Nutr"},{"key":"e_1_2_9_2_72_2","first-page":"703","article-title":"Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects.","volume":"86","author":"Kirke PN","year":"1993","journal-title":"Q J Med"},{"key":"e_1_2_9_2_73_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20454"},{"key":"e_1_2_9_2_74_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30051"},{"key":"e_1_2_9_2_75_2","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420380312"},{"key":"e_1_2_9_2_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(03)00807-X"}],"container-title":["WIREs Developmental Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fwdev.71","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fwdev.71","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wires.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/wdev.71","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T17:22:59Z","timestamp":1695748979000},"score":1,"resource":{"primary":{"URL":"https:\/\/wires.onlinelibrary.wiley.com\/doi\/10.1002\/wdev.71"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,29]]},"references-count":76,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["10.1002\/wdev.71"],"URL":"https:\/\/doi.org\/10.1002\/wdev.71","archive":["Portico"],"relation":{},"ISSN":["1759-7684","1759-7692"],"issn-type":[{"value":"1759-7684","type":"print"},{"value":"1759-7692","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5,29]]}}}