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Event: 1930

Key Event Title

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

altered, inner ear development

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
Altered, inner ear development
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Biological Context

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Level of Biological Organization

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
Organ term

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; 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
otic vesicle formation abnormal

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 Cataia Ives (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
Embryo 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 zebrafish (Danio rerio), a genetically tractable vertebrate, lends itself particularly well as a model system in which to study the ear. Zebrafish do not possess outer or middle ears, but have a fairly typical vertebrate inner ear, the normal development and anatomy of which has been described in a series of atlas-type papers (Haddon and Lewis, 1996; Bang, Sewell and Malicki, 2001). Although the zebrafish ear does not contain a specialized hearing organ—there is no equivalent of the mammalian cochlea—many features are conserved with other vertebrate species (Whitfield, 2002).

Inner ear develops from an ectodermal thickening, the otic placode, visible on either side of the hindbrain from mid-somite stages. In the zebrafish, this placode cavitates to form a hollow ball of epithelium, the otic vesicle, from which all structures of the membranous labyrinth and the neurons of the statoacoustic (VIIIth) ganglion arise (Haddon and Lewis, 1996; Whitfield et al., 2002).

The mature organ, found in all jawed vertebrates, has two functions: it serves as an auditory system, which detects sound waves, and as a vestibular system, which detects linear and angular accelerations, enabling the organism to maintain balance (Whitfield et al., 1996).

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


  • Direct observation of internal anatomic structures of zebrafish embryos. Defects visible under the dissecting microscope (Whitfield, 2002)
  • Comparison of swimming patterns with wild-type fish. Dog-eared embryos are less responsive to vibrational stimuli, fail to maintain balance when swimming, and may circle when disturbed, a behavior characteristic of fish with vestibular defects  (Nicolson et al., 1998)
  • High-throughput behavioral screening method for detecting auditory response defects in zebrafish. Assay monitors a rapid escape reflex in response to a loud sound (Bang et al., 2002).

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 for  Zebrafish, Chick and Mouse (Whitfield, 2015)


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

Bang, P. I. et al. (2002) ‘High-throughput behavioral screening method for detecting auditory response defects in zebrafish’, Journal of Neuroscience Methods, 118(2), pp. 177–187. doi: 10.1016/S0165-0270(02)00118-8.

Bang, P. I., Sewell, W. F. and Malicki, J. J. (2001) ‘Morphology and cell type heterogeneities of the inner ear epithelia in adult and juvenile zebrafish (Danio rerio)’, Journal of Comparative Neurology, 438(2), pp. 173–190. doi: 10.1002/cne.1308.

Haddon, C. and Lewis, J. (1996) ‘Early ear development in the embryo of the zebrafish, Danio rerio’, Journal of Comparative Neurology, 365(1), pp. 113–128. doi: 10.1002/(SICI)1096-9861(19960129)365:1<113::AID-CNE9>3.0.CO;2-6.

Nicolson, T. et al. (1998) ‘Genetic analysis of vertebrate sensory hair cell mechanosensation: The zebrafish circler mutants’, Neuron, 20(2), pp. 271–283. doi: 10.1016/S0896-6273(00)80455-9.

Uribe, P. M. et al. (2013) ‘Aminoglycoside-Induced Hair Cell Death of Inner Ear Organs Causes Functional Deficits in Adult Zebrafish (Danio rerio)’, PLoS ONE, 8(3), p. 58755. doi: 10.1371/journal.pone.0058755.

Whitfield, T. T. et al. (1996) ‘Mutations affecting development of the zebrafish inner ear and lateral line’, Development, 123, pp. 241–254. doi: 10.1242/dev.123.1.241.

Whitfield, T. T. et al. (2002) ‘Development of the zebrafish inner ear’, Developmental Dynamics, 223(4), pp. 427–458. doi: 10.1002/dvdy.10073.

Whitfield, T. T. (2002) ‘Zebrafish as a Model for Hearing and Deafness’, J Neurobiol, 53, pp. 157–171. doi: 10.1002/neu.10123.

Whitfield, T. T. (2015) ‘Development of the inner ear’, Current Opinion in Genetics and Development, 32, pp. 112–118. doi: 10.1016/j.gde.2015.02.006.