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Event: 1557

Key Event Title

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

Neural crest cell migration, reduced

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

Reduced neural crest cell migration

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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

Neural crest cell (NCC) migration is dependent on coordinated expressional alterations of a large number of genes, such as integrins, matrix metalloproteinases, and cytoskeletal components.

The differential regulation of a panel of such genes, has been investigated in an in vitro system, which found that histone deacetylases VPA, TSA, and SAHA exerted similar gene regulatory profiles which were quite distinct from those of other compounds shown to affect NCC migration in a scratch assay (Dreser et al., 2015). A similar experimental setup has applied a broader Affymetrix chip approach to identify biomarkers specific to the inhibition of NCC migration (Pallocca et al., 2016). In vivo evidence for the importance of specific HDACs to NCC migration has been provided by genetic knock down experiments in zebrafish embryos (DeLaurier et al., 2012).

It is likely that the NCC migratory inhibition exerted by HDAC inhibitors is, at least in part, due to the broad transcriptomic impact of HDAC action on histones. However, it cannot be excluded HDAC inhibition could, to some degree, be effects altered acetylation patterns on other proteins, e.g. tubulin acetylation has been shown to be affected by HDAC activity (Hubbert et al., 2002).

How It Is Measured or Detected

In the context of the EMOD/M2AOP prototyping, there are 2 components to the How it is Measured or Detected field, a structured component for adding Assay information and a free text component for unstructured descriptive information.In the free text field, include 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

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NCC migration can be assessed in vitro by scratch assays, and in vivo in developing zebrafish embryos by confocal microscopy with the sox10 fluorescent reporter fishline. Sox10 is a recognized marker of migratory NCCs (Britsch et al., 2001).

Observations 2.0

Observed meausures are instances of assay results that support this Key Event More help

ID	Experimental Effect	Biological Object	Biological Process	Method of Measurement	Notes	Evidence Source ID	Citation (first author, year)

Observed Measures 1.0

Observed meausures are instances of assay results that support this Key Event More help

ID	Stressor	Sample (short_name)	Assay	Effect

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

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
Cellular

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

Organ term

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
HDAC inhibition leads to impeded craniofacial development	KeyEvent	Agnes Aggy (send email)	Under Development: Contributions and Comments Welcome
RALDH2 and cardiovascular developmental defects	KeyEvent	Arthur Author (send email)	Open for comment. Do not cite

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

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Evidence Supporting the 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

Britsch, S., Goerich, D.E., Riethmacher, D., Peirano, R.I., Rossner, M., Nave, K.A., et al. (2001), Genes Dev 15: 66–78.

DeLaurier, A., Nakamura, Y., Braasch, I., Khanna, V., Kato, H., Wakitani, S., et al. (2012), BMC Dev Biol 12: 16.

Dreser, N., Zimmer, B., Dietz, C., Sügis, E., Pallocca, G., Nyffeler, J., et al. (2015), Neurotoxicology 50: 56–70.

Hubbert, C., Guardiola, A., Shao, R., Kawaguchi, Y., Ito, A., Nixon, A., et al. (2002), Nature 417: 455–458.

Pallocca, G., Grinberg, M., Henry, M., Frickey, T., Hengstler, J.G., Waldmann, T., et al. (2016), Arch Toxicol 90: 159–180.