title: Gene expression changes in developing zebrafish as potential markers for rapid developmental neurotoxicity screening.
abstract: Hazard information essential to guide developmental neurotoxicity risk assessments is limited for many chemicals. As developmental neurotoxicity testing using rodents is laborious and expensive, alternative species such as zebrafish are being adapted for rapid toxicity screening. Assessing the developmental neurotoxicity potential of chemicals in a rapid throughput mode will be aided by the identification and characterization of transcriptional biomarkers that can be measured accurately and rapidly. To this end, the developmental expression profiles of ten nervous system genes were characterized in 1 to 6 days post fertilization zebrafish embryos/larvae using quantitative real time PCR (qRT-PCR). Transcripts of synapsinII a (syn2a) and myelin basic protein (mbp) increased throughout development, while transcripts of gap43, elavl3, nkx2.2a, neurogenin1 (ngn1), alpha1-tubulin, and glial fibrillary acidic protein (gfap) initially increased, but subsequently declined. Transcripts for nestin and sonic hedgehog a (shha) decreased during development. We tested the responses of these potential biomarkers to developmental neurotoxicant exposure, and found that the expression profiles of a subset of genes were altered both during and after exposure to sublethal doses of ethanol, a known developmental neurotoxicant. Collectively, these data indicate that transcript levels of the candidate genes change during development in patterns which are consistent with literature reports, and that the expression of the transcripts is perturbed by treatment with a developmental neurotoxicant (ethanol). These results suggest that the expression profiles of these genes may be useful biomarkers for rapid evaluation of the developmental neurotoxicity potential of chemicals.
authors.affiliation: Cellular and Molecular Toxicology Branch, Neurotoxicology Division, United States Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors.forename: Chun-Yang
authors.initials: CY
authors.lastname: Fan
authors.forename: John
authors.initials: J
authors.lastname: Cowden
authors.forename: Steven O
authors.initials: SO
authors.lastname: Simmons
authors.forename: Stephanie
authors.initials: S
authors.lastname: Padilla
authors.forename: Ram
authors.initials: R
authors.lastname: Ramabhadran
mesh_terms: D000818:Animals; D000431:Ethanol / Q000633:toxicity; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D007814:Larva / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods*; D009420:Nervous System / Q000187:drug effects* / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029961:Zebrafish Proteins; D000431:Ethanol