PUBLICATION
Knockdown of a Zebrafish Aryl Hydrocarbon Receptor Repressor (AHRRa) Affects Expression of Genes Related to Photoreceptor Development and Hematopoiesis
- Authors
- Aluru, N., Jenny, M.J., Hahn, M.E.
- ID
- ZDB-PUB-140513-264
- Date
- 2014
- Source
- Toxicological sciences : an official journal of the Society of Toxicology 139: 381-95 (Journal)
- Registered Authors
- Keywords
- AHR, AHRR, TCDD, aryl hydrocarbon receptor, cones, development, dioxin, microarrays, morpholino oligonucleotides, opsins, repressor, zebrafish
- Datasets
- GEO:GSE52229
- MeSH Terms
-
- Animals
- Down-Regulation
- Embryo, Nonmammalian
- Gene Duplication
- Gene Expression Regulation, Developmental/drug effects
- Gene Expression Regulation, Developmental/genetics*
- Gene Knockdown Techniques
- Hematopoiesis/genetics*
- Humans
- Morpholinos/pharmacology
- Repressor Proteins/antagonists & inhibitors*
- Repressor Proteins/genetics
- Retinal Cone Photoreceptor Cells*/drug effects
- Up-Regulation
- Zebrafish/blood*
- Zebrafish/embryology
- Zebrafish/metabolism
- Zebrafish Proteins/antagonists & inhibitors*
- Zebrafish Proteins/genetics
- PubMed
- 24675095 Full text @ Toxicol. Sci.
Citation
Aluru, N., Jenny, M.J., Hahn, M.E. (2014) Knockdown of a Zebrafish Aryl Hydrocarbon Receptor Repressor (AHRRa) Affects Expression of Genes Related to Photoreceptor Development and Hematopoiesis. Toxicological sciences : an official journal of the Society of Toxicology. 139:381-95.
Abstract
The aryl hydrocarbon receptor repressor (AHRR) is a transcriptional repressor of aryl hydrocarbon receptor (AHR) and hypoxia-inducible factor (HIF) and is regulated by an AHR-dependent mechanism. Zebrafish (Danio rerio) possess two AHRR paralogs; AHRRa regulates constitutive AHR signaling during development, whereas AHRRb regulates polyaromatic hydrocarbon-induced gene expression. However, little is known about the endogenous roles and targets of AHRRs. The objective of this study was to elucidate the role of AHRRs during zebrafish development using a loss-of-function approach followed by gene expression analysis. Zebrafish embryos were microinjected with morpholino oligonucleotides against AHRRa or AHRRb to knockdown AHRR protein expression. At 72 h postfertilization (hpf), microarray analysis revealed that the expression of 279 and 116 genes was altered by knockdown of AHRRa and AHRRb, respectively. In AHRRa-morphant embryos, 97 genes were up-regulated and 182 genes were down-regulated. Among the down-regulated genes were several related to photoreceptor function, including cone-specific genes such as several opsins (opn1sw1, opn1sw2, opn1mw1, and opn1lw2), phosphodiesterases (pde6H and pde6C), retinol binding protein (rbp4l), phosducin, and arrestins. Down-regulation was confirmed by RT-PCR and with samples from an independent experiment. The four genes tested (opn1sw1, pde6H, pde6C, and arr3b) were not inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin. AHRRa knockdown also caused up-regulation of embryonic hemoglobin (hbbe3), suggesting a role for AHRR in regulating hematopoiesis. Knockdown of AHRRb caused up-regulation of 31 genes and down-regulation of 85 genes, without enrichment for any specific biological process. Overall, these results suggest that AHRRs may have important roles in development, in addition to their roles in regulating xenobiotic signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping