{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:28:26Z","timestamp":1791332906846,"version":"4.3.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,3,30]],"date-time":"2005-03-30T00:00:00Z","timestamp":1112140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt C"],"published-print":{"date-parts":[[2005,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human neural tube defects (NTD) are a heterogeneous group that exhibit complex inheritance, making it difficult to identify the underlying cause. Due to the uniform genetic background, inbred mouse strains are a more amenable target for genetic studies. We investigated the <jats:italic>loop\u2010tail<\/jats:italic> (<jats:italic>Lp<\/jats:italic>) mouse as a model for the severe NTD, craniorachischisis. A homozygous point mutation was identified in the transmembrane protein <jats:italic>Vangl2<\/jats:italic>, which in <jats:italic>Drosophila<\/jats:italic> has been shown to function in the planar cell polarity (PCP) pathway. Morphological analysis of the <jats:italic>Lp<\/jats:italic> mice shows that the defect results from an abnormally broad floor plate, most likely through a failure in convergent extension. The elevated neural folds remain too far apart to contact, inhibiting neural tube closure. Recently, two other mouse mutants (<jats:italic>crash<\/jats:italic> and <jats:italic>circletail<\/jats:italic>) were described with a similar phenotype to <jats:italic>Lp<\/jats:italic> and were investigated as potentially new alleles. Mapping studies, however, showed that both mutants segregated to distinct loci. In the <jats:italic>crash<\/jats:italic> (<jats:italic>Crsh<\/jats:italic>) mouse, a mutation was identified in <jats:italic>Celsr1<\/jats:italic>, a seven pass transmembrane receptor that encodes a protein orthologous to <jats:italic>Drosophila<\/jats:italic> <jats:italic>Flamingo<\/jats:italic>. Like <jats:italic>Vangl2<\/jats:italic>, this gene also functions in the PCP pathway. While in <jats:italic>circletail<\/jats:italic>, a point mutation was identified introducing a premature stop codon into the apical\u2010basal cell polarity gene <jats:italic>scribble<\/jats:italic> (<jats:italic>Scrb1<\/jats:italic>). We subsequently demonstrated a genetic interaction between all three genes, where double heterozygotes exhibit the same homozygous NTD phenotype. This strongly suggests both a candidate gene pathway and that interaction between independent recessive alleles may be a possible explanation for the complex inheritance in severe human NTD. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.c.30052","type":"journal-article","created":{"date-parts":[[2005,3,30]],"date-time":"2005-03-30T22:16:50Z","timestamp":1112221010000},"page":"42-47","source":"Crossref","is-referenced-by-count":42,"title":["Epithelial cell polarity genes are required for neural tube closure"],"prefix":"10.1002","volume":"135C","author":[{"given":"Kit","family":"Doudney","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Stanier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,3,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/35001108"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1974.tb03442.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008480-199412000-00002"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1181"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00374-9"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.5.976"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6463"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1998.5701"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(98)00029-X"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00164"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)00704-2"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/35011068"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb828"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/90081"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(02)02770-1"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01618"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2001.6638"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.22.2593"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg014"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb716"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(99)00213-0"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(95)80165-I"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jhered.a105976"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00695"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00245-8"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/150.1.199"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.13.2581"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00123"},{"key":"e_1_2_6_30_1","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1242\/dev.128.15.2953","article-title":"Rho kinases play an obligatory role in vertebrate embryonic organogenesis","volume":"128","author":"Wei L","year":"2001","journal-title":"Development"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.6.1149"}],"container-title":["American Journal of Medical Genetics Part C: Seminars in Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.c.30052","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.c.30052","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T21:04:59Z","timestamp":1694466299000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.c.30052"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3,30]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,5,15]]}},"alternative-id":["10.1002\/ajmg.c.30052"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.c.30052","archive":["Portico"],"relation":{},"ISSN":["1552-4868","1552-4876"],"issn-type":[{"value":"1552-4868","type":"print"},{"value":"1552-4876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,3,30]]}}}