A quantitative in vivo assay for craniofacial developmental toxicity of histone deacetylases

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:342

Enthalten in:

Toxicology letters - 342(2021) vom: 15. Mai, Seite 20-25

Sprache:

Englisch

Beteiligte Personen:

Koch, Bjørn E V [VerfasserIn]
Spaink, Herman P [VerfasserIn]
Meijer, Annemarie H [VerfasserIn]

Links:

Volltext

Themen:

122110-53-6
133155-89-2
3X2S926L3Z
614OI1Z5WI
Antibiotics, Antineoplastic
Anticonvulsants
Antifungal Agents
Butyrates
Collagen Type II
Craniofacial development
Developmental and reproductive toxicology
EC 3.5.1.98
Embryonic development
Histone Deacetylases
Histone deacetylase inhibition
Hydroxamic Acids
Journal Article
Luminescent Proteins
Neural crest
Osteogenesis
Peptides
Pivalyloxymethyl butyrate
Toxicity assay
Trapoxin A
Trichostatin A
Valproic Acid
Valproic acid
Zebrafish

Anmerkungen:

Date Completed 22.03.2021

Date Revised 13.12.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.toxlet.2021.02.005

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM321409396