{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T15:52:33Z","timestamp":1792252353134,"version":"4.4.0"},"reference-count":51,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":365,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"name":"Dr. Vaillant Foundation"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Mechanisms of Development"],"published-print":{"date-parts":[[2020,9]]},"DOI":"10.1016\/j.mod.2020.103632","type":"journal-article","created":{"date-parts":[[2020,7,12]],"date-time":"2020-07-12T10:04:14Z","timestamp":1594548254000},"page":"103632","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":24,"special_numbering":"C","title":["The anti-epileptic drug valproic acid causes malformations in the developing craniofacial skeleton of zebrafish larvae"],"prefix":"10.1016","volume":"163","author":[{"given":"I.G.E.","family":"Gebuijs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.R.","family":"Metz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Zethof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.E.L.","family":"Carels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.A.D.T.G.","family":"Wagener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.W.","family":"Von den Hoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"6","key":"10.1016\/j.mod.2020.103632_bb0005","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0126928","article-title":"Zebrafish bone and general physiology are differently affected by hormones or changes in gravity","volume":"10","author":"Aceto","year":"2015","journal-title":"PLoS One"},{"issue":"2","key":"10.1016\/j.mod.2020.103632_bb0010","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.ydbio.2007.03.025","article-title":"Fgf8 haploinsufficiency results in distinct craniofacial defects in adult zebrafish","volume":"306","author":"Albertson","year":"2007","journal-title":"Dev. Biol."},{"issue":"3","key":"10.1016\/j.mod.2020.103632_bb0020","first-page":"233","article-title":"Suivi th\u00e9rapeutique pharmacologique du valproate","volume":"65","author":"Bentu\u00e9-Ferrer","year":"2010","journal-title":"Th\u00e9rapie"},{"issue":"2","key":"10.1016\/j.mod.2020.103632_bb0025","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1615\/CritRevEukarGeneExpr.v21.i2.10","article-title":"Hdac-mediated control of endochondral and intramembranous ossification","volume":"21","author":"Bradley","year":"2011","journal-title":"Crit. Rev. Eukaryot. Gene Expr."},{"issue":"1","key":"10.1016\/j.mod.2020.103632_bb0030","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/jmi.12263","article-title":"Sample holder for axial rotation of specimens in 3D microscopy","volume":"260","author":"Bruns","year":"2015","journal-title":"J. Microsc."},{"issue":"5","key":"10.1016\/j.mod.2020.103632_bb0035","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1111\/j.1471-4159.2005.03457.x","article-title":"Novel targets for valproic acid: up-regulation of melatonin receptors and neurotrophic factors in C6 glioma cells","volume":"95","author":"Castro","year":"2005","journal-title":"J. Neurochem."},{"issue":"9","key":"10.1016\/j.mod.2020.103632_bb0040","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1136\/jmg.32.9.724","article-title":"Fetal valproate syndrome","volume":"32","author":"Clayton-Smith","year":"1995","journal-title":"J. Med. Genet."},{"issue":"2","key":"10.1016\/j.mod.2020.103632_bb0045","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/S0022-3476(80)80517-8","article-title":"Teratogenicity of valproic acid","volume":"97","author":"Dalens","year":"1980","journal-title":"J. Pediatr."},{"issue":"3","key":"10.1016\/j.mod.2020.103632_bb0050","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/ajmg.1320190308","article-title":"The fetal valproate syndrome","volume":"19","author":"DiLiberti","year":"1984","journal-title":"Am. J. Med. Genet."},{"issue":"12","key":"10.1016\/j.mod.2020.103632_bb0055","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0144982","article-title":"Expression of osterix is regulated by FGF and Wnt\/beta-catenin signalling during osteoblast differentiation","volume":"10","author":"Felber","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.mod.2020.103632_bb0060","article-title":"Fgf8a mutation affects craniofacial development and skeletal gene expression in zebrafish larvae","volume":"8","author":"Gebuijs","year":"2019","journal-title":"Biol Open"},{"issue":"3","key":"10.1016\/j.mod.2020.103632_bb0065","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/S0022-3476(81)80743-3","article-title":"Possible teratogenicity of valproic acid","volume":"98","author":"Gomez","year":"1981","journal-title":"J. Pediatr."},{"issue":"7548","key":"10.1016\/j.mod.2020.103632_bb0070","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/nature14436","article-title":"Evolution of vertebrates as viewed from the crest","volume":"520","author":"Green","year":"2015","journal-title":"Nature"},{"issue":"9","key":"10.1016\/j.mod.2020.103632_bb0075","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1096\/fj.04-3425fje","article-title":"Association of valproate-induced teratogenesis with histone deacetylase inhibition in vivo","volume":"19","author":"Gurvich","year":"2005","journal-title":"FASEB J."},{"issue":"14","key":"10.1016\/j.mod.2020.103632_bb0080","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1101\/gad.1809209","article-title":"Epigenetic control of skull morphogenesis by histone deacetylase 8","volume":"23","author":"Haberland","year":"2009","journal-title":"Genes Dev."},{"issue":"21","key":"10.1016\/j.mod.2020.103632_bb0085","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1212\/WNL.0b013e3182574f39","article-title":"Comparative safety of antiepileptic drugs during pregnancy","volume":"78","author":"Hernandez-Diaz","year":"2012","journal-title":"Neurology"},{"issue":"6","key":"10.1016\/j.mod.2020.103632_bb0090","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1586\/ern.10.57","article-title":"Teratogenic effects of antiepileptic drugs","volume":"10","author":"Hill","year":"2010","journal-title":"Expert. Rev. Neurother."},{"issue":"23","key":"10.1016\/j.mod.2020.103632_bb0095","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.1242\/dev.026229","article-title":"Fgf8a induces neural crest indirectly through the activation of Wnt8 in the paraxial mesoderm","volume":"135","author":"Hong","year":"2008","journal-title":"Development"},{"issue":"3","key":"10.1016\/j.mod.2020.103632_bb0100","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.eplepsyres.2013.06.011","article-title":"Valproate reduces collagen and osteonectin in cultured bone cells","volume":"106","author":"Humphrey","year":"2013","journal-title":"Epilepsy Res."},{"issue":"3","key":"10.1016\/j.mod.2020.103632_bb0105","doi-asserted-by":"crossref","first-page":"F207","DOI":"10.1136\/archdischild-2015-308278","article-title":"In utero exposure to valproate increases the risk of isolated cleft palate","volume":"101","author":"Jackson","year":"2016","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"issue":"23","key":"10.1016\/j.mod.2020.103632_bb0110","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1056\/NEJMoa0907328","article-title":"Valproic acid monotherapy in pregnancy and major congenital malformations","volume":"362","author":"Jentink","year":"2010","journal-title":"N. Engl. J. Med."},{"issue":"4","key":"10.1016\/j.mod.2020.103632_bb0115","doi-asserted-by":"crossref","first-page":"275","DOI":"10.5487\/TR.2010.26.4.275","article-title":"Placenta transfer and toxicokinetics of valproic acid in pregnant cynomolgus monkeys","volume":"26","author":"Jeong","year":"2010","journal-title":"Toxicol Res"},{"issue":"4","key":"10.1016\/j.mod.2020.103632_bb0120","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1128\/MCB.22.4.1172-1183.2002","article-title":"Wnt\/beta-catenin\/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway","volume":"22","author":"Jho","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.mod.2020.103632_bb0125","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/1471-2121-9-66","article-title":"Valproic acid induces differentiation and inhibition of proliferation in neural progenitor cells via the beta-catenin-Ras-ERK-p21Cip\/WAF1 pathway","volume":"9","author":"Jung","year":"2008","journal-title":"BMC Cell Biol."},{"issue":"11","key":"10.1016\/j.mod.2020.103632_bb0130","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0047394","article-title":"Skeletogenic fate of zebrafish cranial and trunk neural crest","volume":"7","author":"Kague","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.mod.2020.103632_bb0135","series-title":"Neural Crest: Origin, Migration and Differentiation","author":"Kelsh","year":"2013"},{"issue":"6","key":"10.1016\/j.mod.2020.103632_bb0140","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nrg819","article-title":"Induction of the neural crest: a multigene process","volume":"3","author":"Knecht","year":"2002","journal-title":"Nat Rev Genet"},{"issue":"3","key":"10.1016\/j.mod.2020.103632_bb0160","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1212\/01.wnl.0000227919.81208.b2","article-title":"In utero antiepileptic drug exposure: fetal death and malformations","volume":"67","author":"Meador","year":"2006","journal-title":"Neurology"},{"issue":"12","key":"10.1016\/j.mod.2020.103632_bb0165","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1002\/dvdy.24563","article-title":"Histone deacetylase 1 and 2 are essential for murine neural crest proliferation, pharyngeal arch development, and craniofacial morphogenesis","volume":"246","author":"Milstone","year":"2017","journal-title":"Dev. Dyn."},{"key":"10.1016\/j.mod.2020.103632_bb0170","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/bs.ctdb.2015.07.001","article-title":"Zebrafish craniofacial development: a window into early patterning","volume":"115","author":"Mork","year":"2015","journal-title":"Curr. Top. Dev. Biol."},{"issue":"1","key":"10.1016\/j.mod.2020.103632_bb0175","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1093\/toxsci\/kfs292","article-title":"Exposure to valproic acid inhibits chondrogenesis and osteogenesis in mid-organogenesis mouse limbs","volume":"131","author":"Paradis","year":"2013","journal-title":"Toxicol. Sci."},{"issue":"12","key":"10.1016\/j.mod.2020.103632_bb0180","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1002\/dvdy.22113","article-title":"Normal table of postembryonic zebrafish development: staging by externally visible anatomy of the living fish","volume":"238","author":"Parichy","year":"2009","journal-title":"Dev. Dyn."},{"issue":"2","key":"10.1016\/j.mod.2020.103632_bb0185","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/1520-6866(2001)21:2<121::AID-TCM2>3.0.CO;2-N","article-title":"Action of valproic acid on Xenopus laevis development: teratogenic effects on eyes","volume":"21","author":"Pennati","year":"2001","journal-title":"Teratog. Carcinog. Mutagen."},{"issue":"10","key":"10.1016\/j.mod.2020.103632_bb0190","doi-asserted-by":"crossref","first-page":"695","DOI":"10.2165\/00023210-200216100-00004","article-title":"Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience","volume":"16","author":"Perucca","year":"2002","journal-title":"CNS Drugs"},{"issue":"3","key":"10.1016\/j.mod.2020.103632_bb0195","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1002\/dvdy.20168","article-title":"Histone deacetylase 1 (HDAC-1) required for the normal formation of craniofacial cartilage and pectoral fins of the zebrafish","volume":"231","author":"Pillai","year":"2004","journal-title":"Dev. Dyn."},{"key":"10.1016\/j.mod.2020.103632_bb0200","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.mcn.2016.06.004","article-title":"Valproic acid exposure sequentially activates Wnt and mTOR pathways in rats","volume":"75","author":"Qin","year":"2016","journal-title":"Mol. Cell. Neurosci."},{"issue":"15","key":"10.1016\/j.mod.2020.103632_bb0205","doi-asserted-by":"crossref","DOI":"10.1242\/dev.163386","article-title":"Histone deacetylase activity has an essential role in establishing and maintaining the vertebrate neural crest","volume":"145","author":"Rao","year":"2018","journal-title":"Development"},{"issue":"16","key":"10.1016\/j.mod.2020.103632_bb0210","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1007\/s00018-007-7079-x","article-title":"The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees?","volume":"64","author":"Rosenberg","year":"2007","journal-title":"Cell. Mol. Life Sci."},{"issue":"3","key":"10.1016\/j.mod.2020.103632_bb0215","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1242\/dev.120.3.483","article-title":"Segment and cell type lineage restrictions during pharyngeal arch development in the zebrafish embryo","volume":"120","author":"Schilling","year":"1994","journal-title":"Development"},{"issue":"7","key":"10.1016\/j.mod.2020.103632_bb0220","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"issue":"2","key":"10.1016\/j.mod.2020.103632_bb0225","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1093\/toxsci\/kfv094","article-title":"Gene expression regulation and pathway analysis after valproic acid and carbamazepine exposure in a human embryonic stem cell-based neurodevelopmental toxicity assay","volume":"146","author":"Schulpen","year":"2015","journal-title":"Toxicol. Sci."},{"issue":"2","key":"10.1016\/j.mod.2020.103632_bb0230","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.ydbio.2013.03.008","article-title":"Murine craniofacial development requires Hdac3-mediated repression of Msx gene expression","volume":"377","author":"Singh","year":"2013","journal-title":"Dev. Biol."},{"key":"10.1016\/j.mod.2020.103632_bb0235","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.semcdb.2015.10.003","article-title":"Dysregulated fibroblast growth factor (FGF) signaling in neurological and psychiatric disorders","volume":"53","author":"Turner","year":"2016","journal-title":"Semin. Cell Dev. Biol."},{"issue":"4","key":"10.1016\/j.mod.2020.103632_bb0240","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1111\/ane.12115","article-title":"Associations between particular types of fetal malformation and antiepileptic drug exposure in utero","volume":"128","author":"Vajda","year":"2013","journal-title":"Acta Neurol. Scand."},{"issue":"7","key":"10.1016\/j.mod.2020.103632_bb0245","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2002-3-7-research0034","article-title":"Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes","volume":"3","author":"Vandesompele","year":"2002","journal-title":"Genome Biol."},{"issue":"17","key":"10.1016\/j.mod.2020.103632_bb0250","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.1242\/dev.01943","article-title":"Hedgehog signaling is required for cranial neural crest morphogenesis and chondrogenesis at the midline in the zebrafish skull","volume":"132","author":"Wada","year":"2005","journal-title":"Development"},{"issue":"1","key":"10.1016\/j.mod.2020.103632_bb0255","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/10520290701333558","article-title":"A two-color acid-free cartilage and bone stain for zebrafish larvae","volume":"82","author":"Walker","year":"2007","journal-title":"Biotech Histochem"},{"issue":"2","key":"10.1016\/j.mod.2020.103632_bb0260","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.ydbio.2003.08.010","article-title":"Fgf signalling is required for formation of cartilage in the head","volume":"264","author":"Walshe","year":"2003","journal-title":"Dev. Biol."},{"issue":"8\u20139","key":"10.1016\/j.mod.2020.103632_bb0265","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1080\/10408440591007403","article-title":"Mode of action: inhibition of histone deacetylase, altering WNT-dependent gene expression, and regulation of beta-catenin\u2014developmental effects of valproic acid","volume":"35","author":"Wiltse","year":"2005","journal-title":"Crit. Rev. Toxicol."},{"issue":"2","key":"10.1016\/j.mod.2020.103632_bb0270","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ydbio.2012.09.006","article-title":"FGF signaling transforms non-neural ectoderm into neural crest","volume":"372","author":"Yardley","year":"2012","journal-title":"Dev. Biol."},{"key":"10.1016\/j.mod.2020.103632_bb0275","first-page":"8124501","article-title":"Valproic acid protects primary dopamine neurons from MPP(+)-induced neurotoxicity: involvement of GSK3beta phosphorylation by Akt and ERK through the mitochondrial intrinsic apoptotic pathway","volume":"2017","author":"Zhang","year":"2017","journal-title":"Biomed. Res. Int."}],"container-title":["Mechanisms of Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S092547732030037X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S092547732030037X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T05:27:22Z","timestamp":1760419642000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S092547732030037X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":51,"alternative-id":["S092547732030037X"],"URL":"https:\/\/doi.org\/10.1016\/j.mod.2020.103632","relation":{},"ISSN":["0925-4773"],"issn-type":[{"value":"0925-4773","type":"print"}],"subject":[],"published":{"date-parts":[[2020,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The anti-epileptic drug valproic acid causes malformations in the developing craniofacial skeleton of zebrafish larvae","name":"articletitle","label":"Article Title"},{"value":"Mechanisms of Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.mod.2020.103632","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"103632"}}