{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:23:52Z","timestamp":1791473032882,"version":"4.3.4"},"reference-count":115,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>2,3,7,8-tetrachlorodibenzo-[p]-dioxin (TCDD) is a persistent global pollutant that exhibits a high affinity for the aryl hydrocarbon receptor (AHR), a ligand activated transcription factor. Epidemiological studies have associated AHR agonist exposure with multiple human neuropathologies. Consistent with the human data, research studies using laboratory models have linked pollutant-induced AHR activation to disruptions in learning and memory as well as motor impairments. Our understanding of endogenous AHR functions in brain development is limited and, correspondingly, scientists are still determining which cell types and brain regions are sensitive to AHR modulation. To identify novel phenotypes resulting from pollutant-induced AHR activation and<jats:italic>ahr2<\/jats:italic>loss of function, we utilized the optically transparent zebrafish model. Early embryonic TCDD exposure impaired embryonic brain morphogenesis, resulted in ventriculomegaly, and disrupted neural connectivity in the optic tectum, habenula, cerebellum, and olfactory bulb. Altered neural network formation was accompanied by reduced expression of synaptic vesicle 2. Loss of<jats:italic>ahr2<\/jats:italic>function also impaired nascent network development, but did not affect gross brain or ventricular morphology. To determine whether neural AHR activation was sufficient to disrupt connectivity, we used the Gal4\/UAS system to express a constitutively active AHR specifically in differentiated neurons and observed disruptions only in the cerebellum; thus, suggesting that the phenotypes resulting from global AHR activation likely involve multiple cell types. Consistent with this hypothesis, we found that TCDD exposure reduced the number of oligodendrocyte precursor cells and their derivatives. Together, our findings indicate that proper modulation of AHR signaling is necessary for the growth and maturation of the embryonic zebrafish brain.<\/jats:p>","DOI":"10.3389\/fnmol.2022.1032302","type":"journal-article","created":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T08:49:45Z","timestamp":1669711785000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Proper modulation of AHR signaling is necessary for establishing neural connectivity and oligodendrocyte precursor cell development in the embryonic zebrafish brain"],"prefix":"10.3389","volume":"15","author":[{"given":"Nathan R.","family":"Martin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratna","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle E.","family":"Kossack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel A.","family":"Camarillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layra G.","family":"Cintr\u00f3n-Rivera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph C.","family":"Gawdzik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica S.","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Favour O.","family":"Nwagugo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loes M. 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Med."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1093\/toxsci\/kfh065","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits regression of the common cardinal vein in developing zebrafish","volume":"78","author":"Bello","year":"2004","journal-title":"Toxicol. Sci."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"101","DOI":"10.3389\/fnsys.2011.00101","article-title":"Prey capture behavior evoked by simple visual stimuli in larval zebrafish","volume":"5","author":"Bianco","year":"2011","journal-title":"Front. Syst. Neurosci."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bcp.2016.06.015","article-title":"From dioxin toxicity to putative physiologic functions of the human ah receptor in homeostasis of stem\/progenitor cells","volume":"123","author":"Bock","year":"2017","journal-title":"Biochem. 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Sci."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.immuni.2017.12.012","article-title":"Regulation of the immune response by the aryl hydrocarbon receptor","volume":"48","author":"Guti\u00e9rrez-V\u00e1zquez","year":"2018","journal-title":"Immunity"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.cotox.2017.02.003","article-title":"Diversity as opportunity: insights from 600 million years of AHR evolution","volume":"2","author":"Hahn","year":"2017","journal-title":"Curr Opin Toxicol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1006\/taap.1996.8024","article-title":"Early life stage toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in zebrafish (Danio rerio)","volume":"142","author":"Henry","year":"1997","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1111\/j.1095-8649.2004.0352.x","article-title":"Characterization of TCDD-induced craniofacial malformations and retardation of zebrafish growth","volume":"64","author":"Hill","year":"2004","journal-title":"J. Fish Biol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1093\/toxsci\/kfg241","article-title":"Neurodevelopmental defects in zebrafish (Danio rerio) at environmentally relevant dioxin (TCDD) concentrations","volume":"76","author":"Hill","year":"2003","journal-title":"Toxicol. Sci."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1124\/mol.113.086413","article-title":"Sox 9b is required for epicardium formation and plays a role in TCDD-induced heart malformation in zebrafish","volume":"84","author":"Hofsteen","year":"2013","journal-title":"Mol. Pharmacol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.neuro.2021.07.003","article-title":"The use of tocofersolan as a rescue agent in larval zebrafish exposed to benzo[a]pyrene in early development","volume":"86","author":"Holloway","year":"2021","journal-title":"Neurotoxicology"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"147","DOI":"10.3389\/fncir.2014.00147","article-title":"Rapid development of Purkinje cell excitability, functional cerebellar circuit, and afferent sensory input to cerebellum in zebrafish","volume":"8","author":"Hsieh","year":"2014","journal-title":"Front. Neural Circuits"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1242\/dev.00959","article-title":"The AHR-1 aryl hydrocarbon receptor and its co-factor the AHA-1 aryl hydrocarbon receptor nuclear translocator specify GABAergic neuron cell fate in C. elegans","volume":"131","author":"Huang","year":"2004","journal-title":"Development"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.aquatox.2012.12.009","article-title":"Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the peripheral nervous system of developing red seabream (Pagrus major)","author":"Iida","year":"2013","journal-title":"Aquat. Toxicol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1093\/toxsci\/kfp116","article-title":"Distinct roles of two Zebrafish AHR repressors (AHRRa and AHRRb) in embryonic development and regulating the response to 2,3,7,8-Tetrachlorodibenzo-p-dioxin","volume":"110","author":"Jenny","year":"2009","journal-title":"Toxicol. Sci."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1093\/toxsci\/kfm207","article-title":"Role of AHR2 in the expression of novel cytochrome P450 1 family genes, cell cycle genes, and morphological defects in developing zebra fish exposed to 3,3\u2032,4,4\u2032,5-Pentachlorobiphenyl or 2,3,7,8-Tetrachlorodibenzo-p-dioxin","volume":"100","author":"J\u00f6nsson","year":"2007","journal-title":"Toxicol. Sci."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"9794","DOI":"10.1038\/s41598-017-09621-3","article-title":"AhR-deficiency as a cause of demyelinating disease and inflammation","volume":"7","author":"Juricek","year":"2017","journal-title":"Sci. Rep."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/nn.3357","article-title":"Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis","volume":"16","author":"Kang","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1016\/j.neuroscience.2006.08.070","article-title":"Neurotransmitter receptors in the life and death of oligodendrocytes","volume":"145","author":"K\u00e1rad\u00f3ttir","year":"2007","journal-title":"Neuroscience"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"2806","DOI":"10.1101\/gad.1459706","article-title":"The bHLH-PAS protein spineless is necessary for the diversification of dendrite morphology of drosophila dendritic arborization neurons","volume":"20","author":"Kim","year":"2006","journal-title":"Genes Dev."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"149","DOI":"10.2486\/indhealth.41.149","article-title":"Impact of agent Orange exposure among Korean Vietnam veterans","volume":"41","author":"Kim","year":"2003","journal-title":"Ind. 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Teratol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.ntt.2016.10.006","article-title":"Developmental benzo[a]pyrene (B[a]P) exposure impacts larval behavior and impairs adult learning in zebrafish","volume":"59","author":"Knecht","year":"2017","journal-title":"Neurotoxicol. Teratol."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1242\/dev.118.2.417","article-title":"Zebrafish primary neurons initiate expression of the LIM homeodomain protein Isl-1 at the end of gastrulation","volume":"118","author":"Korzh","year":"1993","journal-title":"Development"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"136723","DOI":"10.1016\/j.chemosphere.2022.136723","article-title":"Environmentally relevant uptake, elimination, and metabolic changes following early embryonic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in zebrafish","volume":"310","author":"Kossack","year":"2023","journal-title":"Chemosphere"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.taap.2011.03.025","article-title":"Role of zebrafish cytochrome P450 CYP1C genes in the reduced mesencephalic vein blood flow caused by activation of AHR2","volume":"253","author":"Kubota","year":"2011","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref1001","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nn2025","article-title":"CNS-derived glia ensheath peripheral nerves and mediate motor root development","volume":"11","author":"Kucenas","year":"2008","journal-title":"Nature Neuroscience"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"10442","DOI":"10.1073\/pnas.190256997","article-title":"Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice","volume":"97","author":"Lahvis","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1093\/toxsci\/kfu111","article-title":"Cardiac myocyte-specific AHR activation phenocopies TCDD-induced toxicity in zebrafish","volume":"141","author":"Lanham","year":"2014","journal-title":"Toxicol. Sci."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1111\/jnc.12130","article-title":"Deletion or activation of the aryl hydrocarbon receptor alters adult hippocampal neurogenesis and contextual fear memory","volume":"125","author":"Latchney","year":"2013","journal-title":"J. Neurochem."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.envint.2019.01.020","article-title":"Early-life exposure to persistent organic pollutants (OCPs, PBDEs, PCBs, PFASs) and attention-deficit\/hyperactivity disorder: a multi-pollutant analysis of a Norwegian birth cohort","volume":"125","author":"Lenters","year":"2019","journal-title":"Environ. Int."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/s13402-014-0206-4","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibits human ovarian cancer cell proliferation","volume":"37","author":"Li","year":"2014","journal-title":"Cell. Oncol. 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Sci."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1289\/ehp.10399","article-title":"Dioxin exposure, from infancy through puberty, produces endocrine disruption and affects human semen quality","volume":"116","author":"Mocarelli","year":"2008","journal-title":"Environ. Health Perspect."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"eaah7029","DOI":"10.1126\/scitranslmed.aah7029","article-title":"Abnormal neurogenesis and cortical growth in congenital heart disease","volume":"9","author":"Morton","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref68","doi-asserted-by":"publisher","DOI":"10.1159\/000525669","article-title":"The Everted amygdala of ray-finned fish: Zebrafish makes a case","author":"Mueller","year":"2022","journal-title":"Brain Behav. Evol."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"45","DOI":"10.3389\/fcell.2016.00045","article-title":"New trends in aryl hydrocarbon receptor biology","volume":"4","author":"Mulero-Navarro","year":"2016","journal-title":"Front. Cell Dev. Biol."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1021\/tx7001965","article-title":"The search for endogenous activators of the aryl hydrocarbon receptor","volume":"21","author":"Nguyen","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1038\/mp.2014.18","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin in breast milk increases autistic traits of 3-year-old children in Vietnam","volume":"19","author":"Nishijo","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/S1047-2797(02)00422-2","article-title":"Serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) levels and thyroid function in air force veterans of the Vietnam war","volume":"13","author":"Pavuk","year":"2003","journal-title":"Ann. Epidemiol."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"e111670","DOI":"10.1371\/journal.pone.0111670","article-title":"Early-life exposure to polycyclic aromatic hydrocarbons and ADHD behavior problems","volume":"9","author":"Perera","year":"2014","journal-title":"PLoS One"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1289\/ehp.1104315","article-title":"Prenatal polycyclic aromatic hydrocarbon (PAH) exposure and child behavior at age 6-7 years","volume":"120","author":"Perera","year":"2012","journal-title":"Environ. Health Perspect."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/1476-069X-8-39","article-title":"Cancer incidence in the population exposed to dioxin after the \"Seveso accident\": twenty years of follow-up","volume":"8","author":"Pesatori","year":"2009","journal-title":"Environ. Health"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1001\/jamapsychiatry.2015.57","article-title":"Effects of prenatal exposure to air pollutants (polycyclic aromatic hydrocarbons) on the development of brain white matter, cognition, and behavior in later childhood","volume":"72","author":"Peterson","year":"2015","journal-title":"JAMA Psychiat."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.scitotenv.2015.07.055","article-title":"Perinatal dioxin exposure and the neurodevelopment of Vietnamese toddlers at 1 year of age","volume":"536","author":"Pham","year":"2015","journal-title":"Sci. Total Environ."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1093\/toxsci\/kfs301","article-title":"Dioxin inhibits zebrafish epicardium and proepicardium development","volume":"131","author":"Plavicki","year":"2013","journal-title":"Toxicol. Sci."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1111\/j.1749-6632.1979.tb56614.x","article-title":"Human health effects from accidental release of tetrachlorodibenzo-p-dioxin (TCDD) at Seveso, Italy","volume":"320","author":"Pocchiari","year":"1979","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.ydbio.2004.02.004","article-title":"The Caenorhabditis elegans aryl hydrocarbon receptor, AHR-1, regulates neuronal development","volume":"270","author":"Qin","year":"2004","journal-title":"Dev. Biol."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1111\/imm.12046","article-title":"The aryl hydrocarbon receptor: a molecular pathway for the environmental control of the immune response","volume":"138","author":"Quintana","year":"2013","journal-title":"Immunology"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1124\/pr.113.007823","article-title":"Aryl hydrocarbon receptor control of adaptive immunity","volume":"65","author":"Quintana","year":"2013","journal-title":"Pharmacol. Rev."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/1471-2148-14-6","article-title":"Genetic variation at aryl hydrocarbon receptor (AHR) loci in populations of Atlantic killifish (Fundulus heteroclitus) inhabiting polluted and reference habitats","volume":"14","author":"Reitzel","year":"2014","journal-title":"BMC Evol. Biol."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2015\/645603","article-title":"Histopathological, ultrastructural, and immunohistochemical assessment of hippocampus structures of rats exposed to TCDD and high doses of tocopherol and acetylsalicylic acid","volume":"2015","author":"Rosi\u0144czuk","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1111\/j.1471-4159.2011.07291.x","article-title":"Aryl hydrocarbon receptor-dependent induction of apoptosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin in cerebellar granule cells from mouse","volume":"118","author":"S\u00e1nchez-Mart\u00edn","year":"2011","journal-title":"J. Neurochem."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1016\/j.pediatrneurol.2015.02.011","article-title":"Homozygous mutation in synaptic vesicle glycoprotein 2A gene results in intractable epilepsy, involuntary movements, microcephaly, and developmental and growth retardation","volume":"52","author":"Serajee","year":"2015","journal-title":"Pediatr. Neurol."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1023\/B:MICS.0000006847.09037.3a","article-title":"Neural cell fate analysis in zebrafish using olig2 BAC transgenics","volume":"25","author":"Shin","year":"2003","journal-title":"Methods Cell Sci."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1046\/j.1439-0272.2000.00394.x","article-title":"Environmental exposure to dioxin: the Seveso experience","volume":"32","author":"Signorini","year":"2000","journal-title":"Andrologia"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.neuron.2013.05.009","article-title":"Sensory neuron fates are distinguished by a transcriptional switch that regulates dendrite branch stabilization","volume":"79","author":"Smith","year":"2013","journal-title":"Neuron"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1093\/toxsci\/kfz075","article-title":"ahr2, but not ahr1a or ahr1b, is required for craniofacial and fin development and TCDD-dependent Cardiotoxicity in Zebrafish","volume":"170","author":"Souder","year":"2019","journal-title":"Toxicol. Sci."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1111\/j.1365-2567.2009.03054.x","article-title":"The aryl hydrocarbon receptor: a perspective on potential roles in the immune system","volume":"127","author":"Stevens","year":"2009","journal-title":"Immunology"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1101\/gad.215802","article-title":"Terminal differentiation of myelin-forming oligodendrocytes depends on the transcription factor Sox10","volume":"16","author":"Stolt","year":"2002","journal-title":"Genes Dev."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"3927","DOI":"10.1021\/acschemneuro.9b00351","article-title":"The synaptic vesicle glycoprotein 2: structure, function, and disease relevance","volume":"10","author":"Stout","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1002\/glia.20981","article-title":"Sox10 is necessary for oligodendrocyte survival following axon wrapping","volume":"58","author":"Takada","year":"2010","journal-title":"Glia"},{"key":"ref95","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.180138","article-title":"Synaptic dysfunction in neurodegenerative and neurodevelopmental diseases: an overview of induced pluripotent stem-cell-based disease models","volume":"8","author":"Taoufik","year":"2018","journal-title":"Open Biol."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.aquatox.2010.05.003","article-title":"Malformation of certain brain blood vessels caused by TCDD activation of Ahr2\/Arnt1 signaling in developing zebrafish","volume":"99","author":"Teraoka","year":"2010","journal-title":"Aquat. Toxicol."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1002\/bdra.20281","article-title":"Zebrafish as a model for developmental neurotoxicity testing","volume":"76","author":"Ton","year":"2006","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"e0147655","DOI":"10.1371\/journal.pone.0147655","article-title":"Impacts of perinatal dioxin exposure on motor coordination and higher cognitive development in Vietnamese preschool children: a five-year follow-up","volume":"11","author":"Tran","year":"2016","journal-title":"PLoS One"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1093\/toxsci\/kfm149","article-title":"Tumor necrosis factor-\u03b1 modulates effects of aryl hydrocarbon receptor ligands on cell proliferation and expression of cytochrome P450 enzymes in rat liver \u201cstem-like\u201d cells","volume":"99","author":"Umannov\u00e1","year":"2007","journal-title":"Toxicol. Sci."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1289\/ehp.1103720","article-title":"Dioxin exposure and cancer risk in the Seveso Women's health study","volume":"119","author":"Warner","year":"2011","journal-title":"Environ. Health Perspect."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1038\/nature04615","article-title":"Stochastic spineless expression creates the retinal mosaic for colour vision","volume":"440","author":"Wernet","year":"2006","journal-title":"Nature"},{"key":"ref102","volume-title":"The Zebrafish book: A guide for the laboratory use of Zebrafish (Danio Rerio)","author":"Westerfield","year":"2000"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1080\/10590500903310047","article-title":"An overview of the effects of dioxins and dioxin-like compounds on vertebrates, as documented in human and ecological epidemiology","volume":"27","author":"White","year":"2009","journal-title":"J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1111\/eva.12470","article-title":"When evolution is the solution to pollution: key principles, and lessons from rapid repeated adaptation of killifish (Fundulus heteroclitus) populations","volume":"10","author":"Whitehead","year":"2017","journal-title":"Evol. Appl."},{"key":"ref105","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1093\/toxsci\/kfi031","article-title":"Aryl hydrocarbon receptor expression and activity in cerebellar granule neuroblasts: implications for development and dioxin neurotoxicity","volume":"83","author":"Williamson","year":"2005","journal-title":"Toxicol. Sci."},{"key":"ref106","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1126\/science.1197296","article-title":"Mechanistic basis of resistance to PCBs in Atlantic tomcod from the Hudson River","volume":"331","author":"Wirgin","year":"2011","journal-title":"Science"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"281","DOI":"10.3967\/bes2019.038","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin promotes proliferation of astrocyte cells via the Akt\/STAT3\/Cyclin D1 pathway","volume":"32","author":"Wu","year":"2019","journal-title":"Biomed. Environ. Sci."},{"key":"ref108","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1124\/mol.108.050435","article-title":"Aryl hydrocarbon receptor-mediated down-regulation of sox9b causes jaw malformation in zebrafish embryos","volume":"74","author":"Xiong","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"ref109","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.toxlet.2013.11.003","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin stimulates proliferation of HAPI microglia by affecting the Akt\/GSK-3\u03b2\/cyclin D1 signaling pathway","volume":"224","author":"Xu","year":"2014","journal-title":"Toxicol. Lett."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1093\/toxsci\/kfn035","article-title":"Influence of TCDD on Zebrafish CYP1B1 transcription during development","volume":"103","author":"Yin","year":"2008","journal-title":"Toxicol. Sci."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"105786","DOI":"10.1016\/j.aquatox.2021.105786","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin exposure disrupts development of the visceral and ocular vasculature","volume":"234","author":"Yue","year":"2021","journal-title":"Aquat. 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