PUBLICATION

Aryl hydrocarbon receptor mediates larval zebrafish fin duplication following exposure to benzofluoranthenes

Authors
Garland, M.A., Geier, M.C., Bugel, S.M., Shankar, P., Dunham, C.L., Brown, J.M., Tilton, S.C., Tanguay, R.L.
ID
ZDB-PUB-200510-12
Date
2020
Source
Toxicological sciences : an official journal of the Society of Toxicology   176(1): 46-64 (Journal)
Registered Authors
Shankar, Prarthana, Tanguay, Robyn L., Tilton, Susan C.
Keywords
RNA sequencing, appendage, benzo[k]fluoranthene
Datasets
GEO:GSE143945
MeSH Terms
  • Animals
  • Embryo, Nonmammalian
  • Fluorenes/toxicity*
  • Larva
  • Polycyclic Aromatic Hydrocarbons/toxicity
  • Receptors, Aryl Hydrocarbon/metabolism*
  • Water Pollutants, Chemical/toxicity*
  • Zebrafish
  • Zebrafish Proteins/metabolism*
PubMed
32384158 Full text @ Toxicol. Sci.
CTD
32384158
Abstract
The aryl hydrocarbon receptor (AHR) mediates developmental toxicity of several xenobiotic classes including polycyclic aromatic hydrocarbons (PAHs). Using embryonic zebrafish, we previously identified four PAHs that caused a novel phenotype among AHR ligands - growth of a lateral, duplicate caudal fin fold. The window of sensitivity to the most potent inducer of this phenotype, benzo[k]fluoranthene (BkF), was prior to 36 hours post-fertilization (hpf), although the phenotype was not manifest until 60 hpf. AHR dependency via Ahr2 was demonstrated using morpholino knockdown. Hepatocyte ablation demonstrated that hepatic metabolism of BkF was not required for the phenotype, nor was it responsible for the window of susceptibility. RNA sequencing performed on caudal trunk tissue from BkF-exposed animals collected at 48, 60, 72, and 96 hpf showed upregulation of genes associated with AHR activation, appendage development, and tissue patterning. Genes encoding fibroblast growth factor and bone morphogenic protein ligands, along with retinaldehyde dehydrogenase, were prominently upregulated. Gene ontology (GO) term analysis revealed that upregulated genes were enriched for mesoderm development and fin regeneration, while downregulated genes were enriched for Wnt signaling and neuronal development. MetaCore (Clarivate Analytics) systems analysis of orthologous human genes predicted that R-SMADs, AP-1, and LEF1 regulated the expression of an enriched number of gene targets across all time points. Our results demonstrate a novel aspect of AHR activity with implications for developmental processes conserved across vertebrate species.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping