trichostatin-a and pivalyloxymethyl-butyrate

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.

Topics: Animals; Animals, Genetically Modified; Antibiotics, Antineoplastic; Anticonvulsants; Antifungal Agents; Butyrates; Collagen Type II; Craniofacial Abnormalities; Gene Expression Regulation, Developmental; Genes, Reporter; Histone Deacetylases; Hydroxamic Acids; Luminescent Proteins; Peptides; Red Fluorescent Protein; Valproic Acid; Zebrafish