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 |
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Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:342 |
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Enthalten in: |
Toxicology letters - 342(2021) vom: 15. Mai, Seite 20-25 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Koch, Bjørn E V [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 22.03.2021 Date Revised 13.12.2023 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.toxlet.2021.02.005 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM321409396 |
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245 | 1 | 2 | |a A quantitative in vivo assay for craniofacial developmental toxicity of histone deacetylases |
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520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Craniofacial development | |
650 | 4 | |a Developmental and reproductive toxicology | |
650 | 4 | |a Embryonic development | |
650 | 4 | |a Histone deacetylase inhibition | |
650 | 4 | |a Neural crest | |
650 | 4 | |a Osteogenesis | |
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