{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T18:23:47Z","timestamp":1774463027280,"version":"3.50.1"},"reference-count":103,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":3059,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Summary<\/jats:title><jats:p>Fetal valproate syndrome (FVS) is caused by in utero exposure to the drug sodium valproate. Valproate is used worldwide for the treatment of epilepsy, as a mood stabiliser and for its pain relieving properties. In addition to birth defects, FVS is associated with an increased risk of autism spectrum disorder (ASD), which is characterised by abnormal behaviours. Valproate perturbs multiple biochemical pathways and alters gene expression through its inhibition of histone deacetylases. Which, if any, of these mechanisms is relevant to the genesis of its behavioural side-effects is unclear. Neuroanatomical changes associated with FVS have been reported and amongst these, altered serotonergic neuronal differentiation is a consistent finding. Altered serotonin homeostasis is also associated with autism. Here we have used a chemical-genetics approach to investigate the underlying molecular defect in a zebrafish FVS model. Valproate causes the selective failure of zebrafish central serotonin expression. It does so by downregulating the proneural gene ascl1b, an ortholog of Ascl1 and a known determinant of serotonergic identity in the mammalian brainstem. Ascl1b is sufficient to rescue serotonin expression in valproate treated embryos. Chemical and genetic blockade of the histone deacetylase Hdac1 downregulates ascl1b, consistent with the Hdac1 mediated silencing of ascl1b expression by valproate. Moreover, tonic Notch signalling is critical for ascl1b repression by valproate. Concomitant blockade of Notch signalling restores ascl1b expression and serotonin expression in both valproate-exposed and hdac1 mutant embryos. Together these data provide a molecular explanation for serotonergic defects in FVS and highlight an epigenetic mechanism for genome-environment interaction in disease.<\/jats:p>","DOI":"10.1242\/dmm.013219","type":"journal-article","created":{"date-parts":[[2013,10,18]],"date-time":"2013-10-18T03:04:03Z","timestamp":1382065443000},"source":"Crossref","is-referenced-by-count":22,"title":["Valproic Acid silencing of<i>ascl1b\/ascl1<\/i>results in the failure of serotonergic differentiation in a zebrafish model of Fetal Valproate Syndrome"],"prefix":"10.1242","author":[{"given":"J.","family":"Jacob","sequence":"first","affiliation":[{"name":"MRC National Institute for Medical Research, Mill Hill, London, UK;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Ribes","sequence":"additional","affiliation":[{"name":"MRC National Institute for Medical Research, Mill Hill, London, UK;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Moore","sequence":"additional","affiliation":[{"name":"MRC National Institute for Medical Research, Mill Hill, London, UK;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. C.","family":"Constable","sequence":"additional","affiliation":[{"name":"MRC National Institute for Medical Research, Mill Hill, London, UK;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Sasai","sequence":"additional","affiliation":[{"name":"MRC National Institute for Medical Research, Mill Hill, London, UK;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. S.","family":"Gerety","sequence":"additional","affiliation":[{"name":"MRC National Institute for Medical Research, Mill Hill, London, UK;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. J.","family":"Martin","sequence":"additional","affiliation":[{"name":"London Research Institute, Cancer Research UK, Lincoln's Inn Fields, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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Biol."},{"key":"2021042513053792300_b2-0070107","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/13810","article-title":"Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2","volume":"23","author":"Amir","year":"1999","journal-title":"Nat. Genet."},{"key":"2021042513053792300_b3-0070107","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1126\/science.1101678","article-title":"Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice","volume":"306","author":"Ansorge","year":"2004","journal-title":"Science"},{"key":"2021042513053792300_b4-0070107","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.ydbio.2009.04.013","article-title":"Anatomy of zebrafish cerebellum and screen for mutations affecting its development","volume":"330","author":"Bae","year":"2009","journal-title":"Dev. 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Neurol. Neurosurg. Psychiatry"},{"key":"2021042513053792300_b11-0070107","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1242\/dev.127.14.3021","article-title":"Misexpression of basic helix-loop-helix genes in the murine cerebral cortex affects cell fate choices and neuronal survival","volume":"127","author":"Cai","year":"2000","journal-title":"Development"},{"key":"2021042513053792300_b12-0070107","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/S0893-133X(96)00239-4","article-title":"Increase in AP-1 transcription factor DNA binding activity by valproic acid","volume":"16","author":"Chen","year":"1997","journal-title":"Neuropsychopharmacology"},{"key":"2021042513053792300_b13-0070107","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1001\/jama.2013.2270","article-title":"Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism","volume":"309","author":"Christensen","year":"2013","journal-title":"JAMA"},{"key":"2021042513053792300_b14-0070107","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/1531-8249(199903)45:3<287::AID-ANA3>3.0.CO;2-9","article-title":"Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children","volume":"45","author":"Chugani","year":"1999","journal-title":"Ann. Neurol."},{"key":"2021042513053792300_b15-0070107","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1002\/ana.410420420","article-title":"Altered serotonin synthesis in the dentatothalamocortical pathway in autistic boys","volume":"42","author":"Chugani","year":"1997","journal-title":"Ann. Neurol."},{"key":"2021042513053792300_b16-0070107","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/sj.mp.4000266","article-title":"Evidence of linkage between the serotonin transporter and autistic disorder","volume":"2","author":"Cook","year":"1997","journal-title":"Mol. 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Psychiatry"},{"key":"2021042513053792300_b20-0070107","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.neulet.2009.12.054","article-title":"Behavior and serotonergic disorders in rats exposed prenatally to valproate: a model for autism","volume":"470","author":"Dufour-Rainfray","year":"2010","journal-title":"Neurosci. Lett."},{"key":"2021042513053792300_b21-0070107","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.neubiorev.2010.12.013","article-title":"Fetal exposure to teratogens: evidence of genes involved in autism","volume":"35","author":"Dufour-Rainfray","year":"2011","journal-title":"Neurosci. Biobehav. Rev."},{"key":"2021042513053792300_b22-0070107","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s11689-011-9092-5","article-title":"Prader-Willi syndrome and autism spectrum disorders: an evolving story","volume":"3","author":"Dykens","year":"2011","journal-title":"J. Neurodevelopmental Disorders"},{"key":"2021042513053792300_b23-0070107","doi-asserted-by":"crossref","first-page":"7311","DOI":"10.1523\/JNEUROSCI.23-19-07311.2003","article-title":"The role of the extracellular signal-regulated kinase signaling pathway in mood modulation","volume":"23","author":"Einat","year":"2003","journal-title":"J. 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Neurobiol."},{"key":"2021042513053792300_b27-0070107","doi-asserted-by":"crossref","first-page":"6969","DOI":"10.1093\/emboj\/20.24.6969","article-title":"Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells","volume":"20","author":"G\u00f6ttlicher","year":"2001","journal-title":"EMBO J."},{"key":"2021042513053792300_b28-0070107","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1634\/theoncologist.12-8-942","article-title":"Valproic acid activates notch-1 signaling and regulates the neuroendocrine phenotype in carcinoid cancer cells","volume":"12","author":"Greenblatt","year":"2007","journal-title":"Oncologist"},{"key":"2021042513053792300_b29-0070107","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/0092-8674(93)90381-Y","article-title":"Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons","volume":"75","author":"Guillemot","year":"1993","journal-title":"Cell"},{"key":"2021042513053792300_b30-0070107","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."},{"key":"2021042513053792300_b31-0070107","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1471-2164-12-24","article-title":"The epigenetic regulator Histone Deacetylase 1 promotes transcription of a core neurogenic programme in zebrafish embryos","volume":"12","author":"Harrison","year":"2011","journal-title":"BMC Genomics"},{"key":"2021042513053792300_b32-0070107","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/0896-6273(92)90027-B","article-title":"Role of the floor plate in axonal patterning in the zebrafish CNS","volume":"9","author":"Hatta","year":"1992","journal-title":"Neuron"},{"key":"2021042513053792300_b33-0070107","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0896-6273(02)01167-4","article-title":"Pet-1 ETS gene plays a critical role in 5-HT neuron development and is required for normal anxiety-like and aggressive behavior","volume":"37","author":"Hendricks","year":"2003","journal-title":"Neuron"},{"key":"2021042513053792300_b34-0070107","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/0887-2333(93)90111-H","article-title":"Effects of the anticonvulsant drug valproic acid and related substances on the early development of the zebrafish (Brachydanio rerio)","volume":"7","author":"Herrmann","year":"1993","journal-title":"Toxicol. In Vitro"},{"key":"2021042513053792300_b35-0070107","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1242\/dev.125.4.599","article-title":"Control of noradrenergic differentiation and Phox2a expression by MASH1 in the central and peripheral nervous system","volume":"125","author":"Hirsch","year":"1998","journal-title":"Development"},{"key":"2021042513053792300_b36-0070107","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/S0140-6736(03)14236-5","article-title":"Targeted treatments for symptom domains in child and adolescent autism","volume":"362","author":"Hollander","year":"2003","journal-title":"Lancet"},{"key":"2021042513053792300_b37-0070107","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1101\/gad.1628008","article-title":"A nonclassical bHLH Rbpj transcription factor complex is required for specification of GABAergic neurons independent of Notch signaling","volume":"22","author":"Hori","year":"2008","journal-title":"Genes Dev."},{"key":"2021042513053792300_b38-0070107","doi-asserted-by":"crossref","first-page":"54","DOI":"10.2174\/156802608783334015","article-title":"Therapeutic potential of gamma-secretase inhibitors and modulators","volume":"8","author":"Imbimbo","year":"2008","journal-title":"Curr. Top. Med. Chem."},{"key":"2021042513053792300_b39-0070107","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0892-0362(99)00083-5","article-title":"Prenatal exposure of rats to valproic acid reproduces the cerebellar anomalies associated with autism","volume":"22","author":"Ingram","year":"2000","journal-title":"Neurotoxicol. Teratol."},{"key":"2021042513053792300_b40-0070107","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S1534-5807(02)00409-4","article-title":"Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta","volume":"4","author":"Itoh","year":"2003","journal-title":"Dev. Cell"},{"key":"2021042513053792300_b41-0070107","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1038\/nn1985","article-title":"Transcriptional repression coordinates the temporal switch from motor to serotonergic neurogenesis","volume":"10","author":"Jacob","year":"2007","journal-title":"Nat. Neurosci."},{"key":"2021042513053792300_b42-0070107","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1242\/dev.034546","article-title":"Insm1 (IA-1) is an essential component of the regulatory network that specifies monoaminergic neuronal phenotypes in the vertebrate hindbrain","volume":"136","author":"Jacob","year":"2009","journal-title":"Development"},{"key":"2021042513053792300_b43-0070107","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/35049541","article-title":"Neuronal specification in the spinal cord: inductive signals and transcriptional codes","volume":"1","author":"Jessell","year":"2000","journal-title":"Nat. Rev. Genet."},{"key":"2021042513053792300_b44-0070107","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/561","article-title":"Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription","volume":"19","author":"Jones","year":"1998","journal-title":"Nat. Genet."},{"key":"2021042513053792300_b45-0070107","doi-asserted-by":"crossref","first-page":"e48975","DOI":"10.1371\/journal.pone.0048975","article-title":"Mice genetically depleted of brain serotonin display social impairments, communication deficits and repetitive behaviors: possible relevance to autism","volume":"7","author":"Kane","year":"2012","journal-title":"PLoS ONE"},{"key":"2021042513053792300_b46-0070107","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2010.03.024","article-title":"Proneural gene-linked neurogenesis in zebrafish cerebellum","volume":"343","author":"Kani","year":"2010","journal-title":"Dev. Biol."},{"key":"2021042513053792300_b47-0070107","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.toxlet.2010.12.018","article-title":"The critical period of valproate exposure to induce autistic symptoms in Sprague-Dawley rats","volume":"201","author":"Kim","year":"2011","journal-title":"Toxicol. Lett."},{"key":"2021042513053792300_b48-0070107","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/aja.1002030302","article-title":"Stages of embryonic development of the zebrafish","volume":"203","author":"Kimmel","year":"1995","journal-title":"Dev. Dyn."},{"key":"2021042513053792300_b49-0070107","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1093\/hmg\/6.13.2233","article-title":"Serotonin transporter (5-HTT) gene variants associated with autism?","volume":"6","author":"Klauck","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"2021042513053792300_b50-0070107","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.psychres.2009.02.008","article-title":"Relationship between whole blood serotonin and repetitive behaviors in autism","volume":"175","author":"Kolevzon","year":"2010","journal-title":"Psychiatry Res."},{"key":"2021042513053792300_b51-0070107","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1172\/JCI19137","article-title":"Cardiac hypertrophy and histone deacetylase-dependent transcriptional repression mediated by the atypical homeodomain protein Hop","volume":"112","author":"Kook","year":"2003","journal-title":"J. Clin. Invest."},{"key":"2021042513053792300_b52-0070107","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1016\/0092-8674(93)90628-4","article-title":"A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos","volume":"75","author":"Krauss","year":"1993","journal-title":"Cell"},{"key":"2021042513053792300_b53-0070107","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.ijdevneu.2009.01.006","article-title":"Observation of fetal brain in a rat valproate-induced autism model: a developmental neurotoxicity study","volume":"27","author":"Kuwagata","year":"2009","journal-title":"Dev. Neurosci."},{"key":"2021042513053792300_b54-0070107","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1471-213X-11-43","article-title":"Two-color fluorescent in situ hybridization in the embryonic zebrafish brain using differential detection systems","volume":"11","author":"Lauter","year":"2011","journal-title":"BMC Dev. Biol."},{"key":"2021042513053792300_b55-0070107","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.jchemneu.2011.05.009","article-title":"The serotonergic system in fish","volume":"41","author":"Lillesaar","year":"2011","journal-title":"J. Chem. Neuroanat."},{"key":"2021042513053792300_b56-0070107","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1002\/dvdy.21095","article-title":"The serotonergic phenotype is acquired by converging genetic mechanisms within the zebrafish central nervous system","volume":"236","author":"Lillesaar","year":"2007","journal-title":"Dev. Dyn."},{"key":"2021042513053792300_b57-0070107","doi-asserted-by":"crossref","first-page":"e55248","DOI":"10.1371\/journal.pone.0055248","article-title":"The amygdala excitatory\/inhibitory balance in a valproate-induced rat autism model","volume":"8","author":"Lin","year":"2013","journal-title":"PLoS ONE"},{"key":"2021042513053792300_b58-0070107","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nrn1847","article-title":"Notch signalling in vertebrate neural development","volume":"7","author":"Louvi","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"2021042513053792300_b59-0070107","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.1158\/0008-5472.CAN-04-2478","article-title":"Valproic acid alters chromatin structure by regulation of chromatin modulation proteins","volume":"65","author":"Marchion","year":"2005","journal-title":"Cancer Res."},{"key":"2021042513053792300_b60-0070107","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1023\/A:1005551523657","article-title":"Repetitive thoughts and behavior in pervasive developmental disorders: treatment with serotonin reuptake inhibitors","volume":"30","author":"McDougle","year":"2000","journal-title":"J. Autism Dev. Disord."},{"key":"2021042513053792300_b61-0070107","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/cne.20280","article-title":"Ontogeny and innervation patterns of dopaminergic, noradrenergic, and serotonergic neurons in larval zebrafish","volume":"480","author":"McLean","year":"2004","journal-title":"J. Comp. Neurol."},{"key":"2021042513053792300_b62-0070107","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1093\/carcin\/bgl167","article-title":"Valproate induces widespread epigenetic reprogramming which involves demethylation of specific genes","volume":"28","author":"Milutinovic","year":"2007","journal-title":"Carcinogenesis"},{"key":"2021042513053792300_b63-0070107","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ijdevneu.2004.05.004","article-title":"Maternal administration of thalidomide or valproic acid causes abnormal serotonergic neurons in the offspring: implication for pathogenesis of autism","volume":"23","author":"Miyazaki","year":"2005","journal-title":"Int. J. Dev. Neurosci."},{"key":"2021042513053792300_b64-0070107","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1097\/00004583-200404000-00016","article-title":"Platelet serotonin levels in pervasive developmental disorders and mental retardation: diagnostic group differences, within-group distribution, and behavioral correlates","volume":"43","author":"Mulder","year":"2004","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"2021042513053792300_b65-0070107","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/ajmg.b.20147","article-title":"Association of tryptophan 2,3 dioxygenase gene polymorphism with autism","volume":"125B","author":"Nabi","year":"2004","journal-title":"Am. J. Med. Genet. B. Neuropsychiatr. Genet."},{"key":"2021042513053792300_b66-0070107","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/j.cell.2009.04.024","article-title":"Abnormal behavior in a chromosome-engineered mouse model for human 15q11-13 duplication seen in autism","volume":"137","author":"Nakatani","year":"2009","journal-title":"Cell"},{"key":"2021042513053792300_b67-0070107","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/30764","article-title":"Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex","volume":"393","author":"Nan","year":"1998","journal-title":"Nature"},{"key":"2021042513053792300_b68-0070107","first-page":"576","article-title":"Increased monoamine concentration in the brain and blood of fetal thalidomide- and valproic acid-exposed rat: putative animal models for autism","volume":"52","author":"Narita","year":"2002","journal-title":"Pediatr. 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Genet."},{"key":"2021042513053792300_b87-0070107","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1242\/dev.126.13.3005","article-title":"her1, a zebrafish pair-rule like gene, acts downstream of notch signalling to control somite development","volume":"126","author":"Takke","year":"1999","journal-title":"Development"},{"key":"2021042513053792300_b88-0070107","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1242\/dev.126.9.1811","article-title":"her4, a zebrafish homologue of the Drosophila neurogenic gene E(spl), is a target of NOTCH signalling","volume":"126","author":"Takke","year":"1999","journal-title":"Development"},{"key":"2021042513053792300_b89-0070107","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/neu.20023","article-title":"Hedgehog and Fgf signaling pathways regulate the development of tphR-expressing serotonergic raphe neurons in zebrafish embryos","volume":"60","author":"Teraoka","year":"2004","journal-title":"J. Neurobiol."},{"key":"2021042513053792300_b90-0070107","doi-asserted-by":"crossref","first-page":"17095","DOI":"10.1073\/pnas.262658999","article-title":"An epigenetic mouse model for molecular and behavioral neuropathologies related to schizophrenia vulnerability","volume":"99","author":"Tremolizzo","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042513053792300_b91-0070107","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.neures.2006.10.018","article-title":"Abnormality of circadian rhythm accompanied by an increase in frontal cortex serotonin in animal model of autism","volume":"57","author":"Tsujino","year":"2007","journal-title":"Neurosci. Res."},{"key":"2021042513053792300_b92-0070107","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1242\/dev.123.1.153","article-title":"Mutations affecting somite formation and patterning in the zebrafish, Danio rerio","volume":"123","author":"van Eeden","year":"1996","journal-title":"Development"},{"key":"2021042513053792300_b93-0070107","doi-asserted-by":"crossref","first-page":"5469","DOI":"10.1073\/pnas.1112345109","article-title":"Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior","volume":"109","author":"Veenstra-VanderWeele","year":"2012","journal-title":"Proc. Natl. Acad. Sci. 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