PUBLICATION
A quantitative in vivo assay for craniofacial developmental toxicity of histone deacetylases
- Authors
- Koch, B.E.V., Spaink, H.P., Meijer, A.H.
- ID
- ZDB-PUB-210215-13
- Date
- 2021
- Source
- Toxicology letters 342: 20-25 (Journal)
- Registered Authors
- Koch, Bjorn, Meijer, Annemarie H., Spaink, Herman P.
- Keywords
- Osteogenesis, craniofacial development, developmental and reproductive toxicology, embryonic development, histone deacetylase inhibition, neural crest, toxicity assay, valproic acid, zebrafish
- MeSH Terms
-
- Collagen Type II/genetics
- Collagen Type II/metabolism*
- Anticonvulsants/toxicity
- Hydroxamic Acids/toxicity*
- Craniofacial Abnormalities/chemically induced*
- Genes, Reporter
- Animals
- Butyrates/toxicity*
- Peptides/toxicity*
- Antifungal Agents/toxicity
- Zebrafish
- Animals, Genetically Modified
- Antibiotics, Antineoplastic/toxicity
- Luminescent Proteins/genetics
- Luminescent Proteins/metabolism
- Gene Expression Regulation, Developmental/drug effects
- Histone Deacetylases/metabolism*
- Valproic Acid/toxicity
- PubMed
- 33581288 Full text @ Toxicol. Lett.
- CTD
- 33581288
Citation
Koch, B.E.V., Spaink, H.P., Meijer, A.H. (2021) A quantitative in vivo assay for craniofacial developmental toxicity of histone deacetylases. Toxicology letters. 342:20-25.
Abstract
Many bony features of the face develop from endochondral ossification of preexisting collagen-rich cartilage structures. The proper development of these cartilage structures is essential to the morphological formation of the face. The developmental programs governing the formation of the pre-bone facial cartilages are sensitive to chemical compounds that disturb histone acetylation patterns and chromatin structure. We have taken advantage of this fact to develop a quantitative morphological assay of craniofacial developmental toxicity based on the distortion and deterioration of facial cartilage structures in zebrafish larvae upon exposure to increasing concentrations of several well-described histone deacetylase inhibitors. In this assay, we measure the angle formed by the developing ceratohyal bone as a precise, sensitive and quantitative proxy for the overall developmental status of facial cartilages. Using the well-established developmental toxicant and histone deacetylase-inhibiting compound valproic acid along with 12 structurally related compounds, we demonstrate the applicability of the ceratohyal angle assay to investigate structure-activity relationships.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping