{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:22:49Z","timestamp":1792156969080,"version":"4.4.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,3,4]]},"abstract":"\n Neural tube defects (NTDs) are very frequent congenital abnormalities in humans. Recently, we have documented independent association of\n Vangl1<\/jats:italic>\n and\n Vangl2<\/jats:italic>\n gene mutations with NTDs. In the Looptail mouse, homozygosity (but not heterozygosity) for loss-of-function alleles at\n Vangl2<\/jats:italic>\n causes the severe NTD craniorachischisis, whereas heterozygosity for mutant variants of\n VANGL1<\/jats:italic>\n is associated with NTDs in a human cohort of sporadic and familial cases. To understand the role of\n Vangl1<\/jats:italic>\n in normal development, we created a mouse mutant with an inactivating mutation at\n Vangl1<\/jats:italic>\n (\n \n Vangl1\n gt<\/jats:sup>\n <\/jats:italic>\n ).\n Vangl1<\/jats:italic>\n shows a dynamic pattern of expression in the developing neural tube and notochord at the time of neural tube closure.\n Vangl1<\/jats:italic>\n \n gt<\/jats:italic>\n \/+\n <\/jats:sup>\n heterozygotes and\n \n Vangl1\n gt\/gt<\/jats:sup>\n <\/jats:italic>\n homozygotes are viable and fertile, although\n \n Vangl1\n gt\/gt<\/jats:sup>\n <\/jats:italic>\n display subtle alterations in polarity of inner hair cells of the cochlea. Remarkably, and as opposed to healthy\n Vangl1<\/jats:italic>\n \n gt<\/jats:italic>\n \/+\n <\/jats:sup>\n and\n Vangl2<\/jats:italic>\n \n lp<\/jats:italic>\n \/+\n <\/jats:sup>\n heterozygotes,\n Vangl1<\/jats:italic>\n \n gt<\/jats:italic>\n \/+\n <\/jats:sup>\n ;\n Vangl2<\/jats:italic>\n \n lp<\/jats:italic>\n \/+\n <\/jats:sup>\n double heterozygotes show profound developmental defects that include severe craniorachischisis, inner ear defects (disorganization of the stereociliary bundles of hair cells of the organ of Corti), and cardiac abnormality (aberrant right subclavian artery). These results show that genetic interaction between\n Vangl1<\/jats:italic>\n and\n Vangl2<\/jats:italic>\n genes causes neural tube defects and raise the possibility that interaction between individual\n Vangl<\/jats:italic>\n genes and other genetic loci and\/or environmental factors may additionally contribute to the etiology of NTDs.\n <\/jats:p>","DOI":"10.1073\/pnas.0712126105","type":"journal-article","created":{"date-parts":[[2008,2,22]],"date-time":"2008-02-22T21:31:01Z","timestamp":1203715861000},"page":"3449-3454","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":166,"title":["Genetic interaction between members of the Vangl family causes neural tube defects in mice"],"prefix":"10.1073","volume":"105","author":[{"given":"Elena","family":"Torban","sequence":"first","affiliation":[{"name":"*Department of Biochemistry, McGill University, Montreal, QC, Canada H3G 1Y6;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie","family":"Patenaude","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry, McGill University, Montreal, QC, Canada H3G 1Y6;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Severine","family":"Leclerc","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics Unit, Ste-Justine Hospital, Montreal, QC, Canada H3T 1C5; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Staci","family":"Rakowiecki","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Gauthier","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry, McGill University, Montreal, QC, Canada H3G 1Y6;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Andelfinger","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics Unit, Ste-Justine Hospital, Montreal, QC, Canada H3T 1C5; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas J.","family":"Epstein","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Gros","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry, McGill University, Montreal, QC, Canada H3G 1Y6;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,3,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.44.s3.2.x"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199911113412006"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2007.00793.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.42.083001.110955"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1181"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jhered.a105976"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01618"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000154912.08695.88"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/90081"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.22.2593"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6493"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.modgep.2006.07.007"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/150.1.199"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.6.1149"},{"key":"e_1_3_3_15_2","first-page":"738","article-title":"Planar cell polarity signaling: a common mechanism for cellular polarization.","volume":"73","author":"Jenny A","year":"2006","unstructured":"A Jenny, M Mlodzik, Planar cell polarity signaling: a common mechanism for cellular polarization. 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