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
  • Animals
  • Animals, Genetically Modified
  • Antibiotics, Antineoplastic/toxicity
  • Anticonvulsants/toxicity
  • Antifungal Agents/toxicity
  • Butyrates/toxicity*
  • Collagen Type II/genetics
  • Collagen Type II/metabolism*
  • Craniofacial Abnormalities/chemically induced*
  • Gene Expression Regulation, Developmental/drug effects
  • Genes, Reporter
  • Histone Deacetylases/metabolism*
  • Hydroxamic Acids/toxicity*
  • Luminescent Proteins/genetics
  • Luminescent Proteins/metabolism
  • Peptides/toxicity*
  • Valproic Acid/toxicity
  • Zebrafish
PubMed
33581288 Full text @ Toxicol. Lett.
CTD
33581288
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
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping