PUBLICATION
Neuro-developmental defects in zebrafish (Danio rerio) at environmentally relevant dioxin (TCDD) concentrations
- Authors
- Hill, A., Howard, C.V., Strähle, U., and Cossins, A.
- ID
- ZDB-PUB-031111-10
- Date
- 2003
- Source
- Toxicological sciences : an official journal of the Society of Toxicology 76(2): 392-399 (Journal)
- Registered Authors
- Hill, Adrian, Strähle, Uwe
- Keywords
- neurotoxicity; TCDD; zebrafish; embryo; sonic hedgehog; neurogenin
- MeSH Terms
-
- Environmental Pollutants/toxicity*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Apoptosis/drug effects
- In Situ Hybridization
- Gene Expression Regulation, Developmental/drug effects
- Embryo, Nonmammalian/abnormalities
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/metabolism
- Nerve Tissue Proteins/genetics
- Zebrafish/embryology*
- Zebrafish/genetics
- Trans-Activators/genetics
- Dose-Response Relationship, Drug
- Hedgehog Proteins
- Animals, Genetically Modified
- Brain/abnormalities
- Brain/drug effects*
- Animals
- Transcription Factors/genetics
- Basic Helix-Loop-Helix Transcription Factors
- PubMed
- 14600291 Full text @ Toxicol. Sci.
- CTD
- 14600291
Citation
Hill, A., Howard, C.V., Strähle, U., and Cossins, A. (2003) Neuro-developmental defects in zebrafish (Danio rerio) at environmentally relevant dioxin (TCDD) concentrations. Toxicological sciences : an official journal of the Society of Toxicology. 76(2):392-399.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping