ToxSci Advance Access originally published online on July 22, 2008
Toxicological Sciences 2008 106(1):103-112; doi:10.1093/toxsci/kfn145
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Exposure to Sodium Metam during Zebrafish Somitogenesis Results in Early Transcriptional Indicators of the Ensuing Neuronal and Muscular Dysfunction
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* Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, Washington
Department of Environmental & Molecular Toxicology
Environmental Health Sciences Center
Marine & Freshwater Biomedical Sciences Center, Oregon State University, Corvallis, Oregon 97331
For correspondence via. E-mail: robert.tanguay{at}oregonstate.edu. Fax: 541-737-7966.
Received April 29, 2008; accepted July 7, 2008
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Abstract |
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Exposures to sodium metam (NaM) within the developmental period of somitogenesis (10- to 18-h postfertilization [hpf]) results in easily detectable distortions of the notochord by 24 hpf in the developing zebrafish. We hypothesized that NaM-induced transcriptional changes during somitogenesis would reveal the major molecular targets in the zebrafish embryo. Embryos were exposed to NaM beginning at 4 hpf (1000 cells) and total RNA was isolated from embryos at the 3 somite (11 hpf), 10 somite (14 hpf), 18 somite (18 hpf), and larval (24 hpf) stages of development. Using the Affymetrix zebrafish gene array we observed relatively few mRNAs differentially regulated at least twofold at each time point (11 hpf, 101 genes; 14 hpf, 151; 18 hpf, 154; 24 hpf, 33). The transcriptional profiles reveal neurodevelopment and myogenesis as the two primary targets of NaM developmental exposure. Quantitative PCR of several muscle and neuronal genes confirmed the array response. We also followed the structural development of the peripheral nervous system under NaM exposure using antibodies against neuronal structural proteins. Although there was no change in the onset of antibody staining, profound alterations became apparent during the period in which the notochord becomes distorted (> 18 hpf). Motor neuron development observed with the Tg(NBT:MAPT-GFP)zc1 transgenic zebrafish and a primary motor neuron specific antibody showed similar timing in the structural alterations observed in these cell types. Further study of the interactions of dithiocarbamates with the regulatory elements of fast muscle development and neurodevelopment is warranted.
Key Words: developmental toxicity; dithiocarbamate; copper; pesticide.