TitleExposure to sodium metam during zebrafish somitogenesis results in early transcriptional indicators of the ensuing neuronal and muscular dysfunction.
Publication TypeJournal Article
Year of Publication2008
AuthorsTilton, F, Tanguay, RL
JournalToxicol Sci
Volume106
Issue1
Pagination103-12
Date Published2008 Nov
ISSN1096-0929
KeywordsAnimals, Gene Expression Profiling, Gene Expression Regulation, Developmental, Motor Neurons, Muscle Development, Neurogenesis, Notochord, Oligonucleotide Array Sequence Analysis, Peripheral Nervous System, Pesticides, Polymerase Chain Reaction, RNA, Messenger, Thiocarbamates, Time Factors, Transcription, Genetic, Water Pollutants, Chemical, Zebrafish
Abstract

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.

DOI10.1093/toxsci/kfn145
Alternate JournalToxicol. Sci.
PubMed ID18648088
PubMed Central IDPMC3272709
Grant ListP30 ES000210 / ES / NIEHS NIH HHS / United States