Neurodevelopmental defects in zebrafish (Danio rerio) at environmentally relevant dioxin (TCDD) concentrations.
Persistent ecotoxicants, such as dioxin and PCBs, are thought to pose one of the greatest threats to public and ecological health in the industrial world. These compounds cause a range of macroscopic malformations, particularly to the craniofacial apparatus and cardiovascular system during vertebrate development. However, little is known about microscopic effects, especially on the sensitive early life stages or on the molecular basis of developmental neurotoxicity. Using zebrafish (Danio rerio), we have explored neurological deficits caused by early-life exposure to environmentally relevant concentrations of dioxin. We show, using a quantitative stereological technique, that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) substantially reduces the capacity for embryonic brain development, causing a 30% reduction in total neuronal number in the 168-h larval brain. Using transgenic GFP-expressing zebrafish lines, we link this to decreased expression of key developmentally regulated genes, namely neurogenin and sonic hedgehog. This disruption of neuronal development provides the basis for understanding the neurotoxic effects of these compounds.
Laboratory for Environmental Gene Regulation, School of Biological Sciences, Biosciences Building, University of Liverpool, Crown Street, Liverpool Merseyside L69 7ZB, United Kingdom. ajhill@pharmacy.wisc.edu
Adrian
A
Hill
C Vyvyan
CV
Howard
Uwe
U
Strahle
Andrew
A
Cossins
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000187:drug effects; D051792:Basic Helix-Loop-Helix Proteins; D001921:Brain / Q000002:abnormalities / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects* / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D009419:Nerve Tissue Proteins / Q000235:genetics; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D004785:Environmental Pollutants; D053823:Hedgehog Proteins; D009419:Nerve Tissue Proteins; D000072317:Polychlorinated Dibenzodioxins; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; C486337:neurog1 protein, zebrafish