PUBLICATION
Transcriptional responses of zebrafish embryos exposed to potential sonic hedgehog pathway interfering compounds deviate from expression profiles of cyclopamine
- Authors
- Büttner, A., Busch, W., Klüver, N., Giannis, A., and Scholz, S.
- ID
- ZDB-PUB-120125-36
- Date
- 2012
- Source
- Reproductive toxicology (Elmsford, N.Y.) 33(2): 254-263 (Journal)
- Registered Authors
- Klüver, Nils
- Keywords
- hedgehog, zebrafish, cyclopamine, Hspb11, SANT-2, GANT-61
- Datasets
- GEO:GSE29357
- MeSH Terms
-
- Animals
- Benzamides/toxicity*
- Benzimidazoles/toxicity*
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Gene Expression Profiling
- Gene Expression Regulation, Developmental/drug effects
- Hedgehog Proteins/agonists
- Hedgehog Proteins/antagonists & inhibitors*
- Hedgehog Proteins/genetics
- Pyridines/toxicity*
- Pyrimidines/toxicity*
- Transcription, Genetic
- Veratrum Alkaloids/toxicity*
- Zebrafish
- Zebrafish Proteins/genetics*
- PubMed
- 22265815 Full text @ Reprod. Toxicol.
- CTD
- 22265815
Citation
Büttner, A., Busch, W., Klüver, N., Giannis, A., and Scholz, S. (2012) Transcriptional responses of zebrafish embryos exposed to potential sonic hedgehog pathway interfering compounds deviate from expression profiles of cyclopamine. Reproductive toxicology (Elmsford, N.Y.). 33(2):254-263.
Abstract
The molecular responses of two small molecules, SANT-2 and GANT-61, potentially interfering with the sonic hedgehog pathway (Shh) have been studied in zebrafish embryos by microarray analysis. For both compounds and the positive reference cyclopamine previous reporter gene assays for the transcription factor Gli1 have indicated an inhibition of the hedgehog signaling pathway. In zebrafish embryos a typical phenotype (cyclopia) associated with Shh interference was only observed for cyclopamine. Furthermore, only cyclopamine led to the repression of genes specifically associated with hedgehog signaling and confirmed published microarray data. In contrast to these data hspb11 was additionally identified as the most pronounced down-regulated genes for exposure to cyclopamine. No or different effects on gene expression patterns were provoked by SANT-2 or GANT-61, respectively. Reasons for the discrepancies between cellular reporter and the zebrafish embryo assay and potential implications for the identification of compounds interfering with specific developmental pathways are discussed.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping