PUBLICATION

Exposure to sodium metam during zebrafish somitogenesis results in early transcriptional indicators of the ensuing neuronal and muscular dysfunction

Authors
Tilton, F., and Tanguay, R.L.
ID
ZDB-PUB-080728-9
Date
2008
Source
Toxicological sciences : an official journal of the Society of Toxicology   106(1): 103-112 (Journal)
Registered Authors
Tanguay, Robyn L., Tilton, Fred
Keywords
developmental toxicity, dithiocarbamate, copper, pesticide
MeSH Terms
  • Animals
  • Gene Expression Profiling/methods
  • Gene Expression Regulation, Developmental/drug effects*
  • Motor Neurons/drug effects
  • Muscle Development/drug effects*
  • Muscle Development/genetics
  • Neurogenesis/drug effects*
  • Neurogenesis/genetics
  • Notochord/drug effects
  • Oligonucleotide Array Sequence Analysis
  • Peripheral Nervous System/drug effects
  • Peripheral Nervous System/embryology
  • Pesticides/toxicity*
  • Polymerase Chain Reaction
  • RNA, Messenger/metabolism
  • Thiocarbamates/toxicity*
  • Time Factors
  • Transcription, Genetic/drug effects*
  • Water Pollutants, Chemical/toxicity*
  • Zebrafish/embryology
  • Zebrafish/genetics*
PubMed
18648088 Full text @ Toxicol. Sci.
CTD
18648088
Abstract
Exposures to sodium metam (NaM) within the developmental period of somitogenesis (10-18 hours post fertilization (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 2-fold 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. While there was no change in the onset of antibody staining, profound alterations became apparent during the period in which the notochord becomes distorted (>18hpf). 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 DTCs with the regulatory elements of fast muscle development and neurodevelopment is warranted.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping