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Event: 2020

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Decrease, sox9 expression

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Decrease, sox9 expression
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Molecular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Cell term
eukaryotic cell

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
gene expression decreased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
Ahr mediated early stage mortality via craniofacial malformations KeyEvent Prarthana Shankar (send email) Under development: Not open for comment. Do not cite Under Review
Ahr mediated early stage mortality via cardiovascular toxicity KeyEvent Prarthana Shankar (send email) Under development: Not open for comment. Do not cite Under Review

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
zebrafish Danio rerio High NCBI
human Homo sapiens High NCBI
mouse Mus musculus High NCBI
rat Rattus norvegicus High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
Embryo High
Development High

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Unspecific High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help
  • The sox family of proteins are a group of highly conserved transcriptional regulators that are present in most groups of animals from invertebrates and unicellular organisms (Phochanukul and Russell 2010) to the more complex vertebrates.
  • Sox proteins are characterized by containing the highly conserved high mobility group (HMG) domain, and around 20 different sox proteins have been discovered in mice and humans to date (Jo et al., 2014).
  • Sox9, which is part of the soxE subgroup, was initially discovered as the gene underlying campomelic dysplasia (CD), a haplosufficiency disorder characterized by abnormal chondrogenesis, as well as autosomal XY sex reversal from males to females (Wagner et al., 1994).
  • Since then, sox9 has been implicated in several functions such as in chondrogenesis, skeletal development, male gonad genesis, development of mesodermal tissues such as cardiac valves and septa, and pyloric sphincter, in ectoderm development (neural stem cells, gliogenesis, and neural stem cells), in hair follicle stem cells, retinal progenitor cells, and the otic placode, and during endoderm development impacting the pancreas, liver, intestine, and lungs. The developmental functions of sox9 have been comprehensively reviewed (Jo et al., 2014; Kawaguchi 2013; Lee and Saint-Jeannet 2011; Lefebvre and Dvir-Ginzberg 2017).
  • Several of sox9’s functions are hypothesized to take place as a result of its role as a repressor of the Wnt/B-catenin signaling pathway. Of note, the canonical Wnt signaling pathway promotes chondrocyte differentiation in a sox9-dependent manner (Yano et al., 2005).
  • Sox9b (one of two paralogs of the sox9 gene in zebrafish) is one of the most reduced transcripts in the jaw upon TCDD exposure in zebrafish which causes severe lower jaw defects (Xiong et al., 2008), supporting role of sox9’s repression in craniofacial defects.

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

References

List of the literature that was cited for this KE description. More help