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Event: 1905

Key Event Title

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

eya1 expression, inhibited

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
eya1 expression, inhibited
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Biological Context

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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

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

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
GSK3beta inactivation leads to increased mortality KeyEvent Vid Modic (send email) Open for citation & comment

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

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
During brain development High

Sex Applicability

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

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

Eya1 is predicted to have protein tyrosine phosphatase activity. Involved in adenohypophysis development; otic vesicle morphogenesis; and otolith development. Predicted to localize to nucleus. Is expressed in several structures, including adenohypophyseal placode; brain; ectoderm; head; and lateral line system. Orthologous to human EYA1 (EYA transcriptional coactivator and phosphatase 1) (ZFIN Gene: Eya1, n.d.).

Eyes absent (Eya) genes regulate organogenesis in both vertebrates and invertebrates. Mutations in human EYA1 cause congenital Branchio-Oto-Renal (BOR) syndrome and hereditary syndromic deafness, while targeted inactivation of murine Eya1 impairs early developmental processes in multiple organs, including ear, kidney and skeletal system (Kozlowski et al., 2005; Xu et al., 2002).

In zebrafish, the eya1 gene is widely expressed in placode-derived sensory organs during embryogenesis. Eya1 function appears to be primarily required for survival of sensory hair cells in the developing ear and lateral line neuromasts (Kozlowski et al., 2005).

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

Inhibition of expression can be measured with reverse transcription polymerase chain reaction (RT-PCR). This technique is primarily used to measure the amount of specific RNA which is achieved by monitoring the amplification reaction using fluorescence, a technique called real-time PCR or quantitative PCR (qPCR) (Wong & Medrano, 2005). Combined RT-PCR and qPCR are routinely used for analysis of gene expression.

Domain of Applicability

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

Evidence was provided zebrafish (Kozlowski et al., 2005), Drosophila and vertebrates (Li et al., 2003; Zimmerman et al., 1997), and human (Abdelhak et al., 1997)

References

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

Abdelhak, S., Kalatzis, V., Heilig, R., Compain, S., Samoson, D., Vincent, C., Weil, D., Cruaud, C., Sahly, I., Leibovici, M., Bitner-Glindzicz, M., & Francis, M. (1997). A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. Nature Genetics, 15, 157–167. https://doi.org/10.1038/ng0297-157

Kozlowski, D. J., Whitfield, T. T., Hukriede, N. A., Lam, W. K., & Weinberg, E. S. (2005). The zebrafish dog-eared mutation disrupts eya1, a gene required for cell survival and differentiation in the inner ear and lateral line. Developmental Biology, 277(1), 27–41. https://doi.org/10.1016/j.ydbio.2004.08.033

Li, X., Oghi, K. A., Zhang, J., Krones, A., Bush, K. T., Glass, C. K., Nigam, S. K., Aggarwal, A. K., Maas, R., Rose, D. W., & Rosenfeld, M. G. (2003). Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature, 426(6964), 247–254. https://doi.org/10.1038/nature02083

Wong, M. L., & Medrano, J. F. (2005). Real-time PCR for mRNA quantitation. 39(1), 75–85. https://doi.org/10.2144/05391RV01

Xu, P.-X., Weiming, Z., Laclef, C., Maire, P., Maas L., R., Peters, H., & Xin, X. (2002). Eya1is required for the morphogenesis of mammalian thymus, parathyroid and thyroid. Development, 129, 3033–3044.

ZFIN Gene: eya1. (n.d.). Retrieved April 12, 2021, from https://zfin.org/ZDB-GENE-990712-18

Zimmerman, J. E., Bui, Q. T., Kur Steingrimsson, E. [, Nagle, D. L., Fu, W., Genin, A., Spinner, N. B., Copeland, N. G., Jenkins, N. A., Bucan, M., & Bonini, N. M. (1997). Cloning and Characterization of Two Vertebrate Homologs of the Drosophila eyes absent Gene. Development, 124(23), 4819–4826.