
This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Aop: 274
Title
Histone deacetylase inhibition leads to impeded craniofacial development
Short name
Graphical Representation
Contributors
- Marvin Martens
Status
Author status | OECD status | OECD project | SAAOP status |
---|---|---|---|
Under development: Not open for comment. Do not cite |
This AOP was last modified on December 20, 2018 04:39
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Histone deacetylase inhibition | February 10, 2020 03:09 |
Neural crest cell migration, reduced | December 20, 2018 04:10 |
Collagen production, reduced | December 20, 2018 04:15 |
Facial cartilage structures are reduced in size and morphologically distorted | December 20, 2018 04:16 |
Histone deacetylase inhibition leads to Reduced neural crest cell migration | December 20, 2018 04:22 |
Histone deacetylase inhibition leads to Reduced collagen production | December 20, 2018 04:33 |
Reduced neural crest cell migration leads to Reduced collagen production | December 20, 2018 04:27 |
Reduced collagen production leads to Smaller and morphologically distorted facial cartilage structures | December 20, 2018 04:30 |
Valproic acid | December 20, 2018 04:35 |
Butyrate | January 21, 2018 20:39 |
Trichostatin A | January 21, 2018 20:39 |
Suberoylanilide hydroxamic acid | December 20, 2018 04:36 |
MS-275 | December 20, 2018 04:37 |
Apicidin | December 20, 2018 04:37 |
Abstract
Histone deacetylases (HDACs) regulate gene expression through modulating chromatin structure and are known to impact many aspects of development in animals. Several compounds have been found to inhibit the action of HDACs leading to various adverse outcomes. This AOP aims to describe the sequence of events by which HDAC inhibition leads to impeded craniofacial development. The MIE is the inhibition, at early embryonic stages, of histone deacetylases. This leads to inhibition of cranial neural crest cell migration and inhibition of chondrocyte differentiation. The attenuation of chondrocyte differentiation reduces the production of collagen, a key structural component of cartilage, resulting in the reduced size and morphologically distorted facial cartilage features. This AOP concerns very specific developmental effects of an MIE which has very broad gene regulatory implications. This means that the progression through KEs and AO are mainly applicable at early developmental stages prior to neural crest migration and chondrocyte differentiation. The AOP is linked to case study 2, concerning the developmental and reproductive toxicity of valproic acid (VPA) and several structural homologs. One of the well-described developmental toxicity effects of fetal VPA exposure is craniofacial deformities.
Background (optional)
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Sequence | Type | Event ID | Title | Short name |
---|
1 | MIE | 1502 | Histone deacetylase inhibition | Histone deacetylase inhibition |
2 | KE | 1557 | Neural crest cell migration, reduced | Reduced neural crest cell migration |
3 | KE | 1558 | Collagen production, reduced | Reduced collagen production |
4 | AO | 1559 | Facial cartilage structures are reduced in size and morphologically distorted | Smaller and morphologically distorted facial cartilage structures |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
---|
Histone deacetylase inhibition leads to Reduced neural crest cell migration | adjacent | Not Specified | Not Specified |
Reduced neural crest cell migration leads to Reduced collagen production | adjacent | Not Specified | Not Specified |
Reduced collagen production leads to Smaller and morphologically distorted facial cartilage structures | adjacent | Not Specified | Not Specified |
Histone deacetylase inhibition leads to Reduced collagen production | non-adjacent | Not Specified | Not Specified |
Network View
Stressors
Name | Evidence Term |
---|---|
Valproic acid | |
Butyrate | |
Trichostatin A | |
Suberoylanilide hydroxamic acid | |
MS-275 | |
Apicidin |