Aop: 410


Each AOP should be given a descriptive title that takes the form “MIE leading to AO”. For example, “Aromatase inhibition [MIE] leading to reproductive dysfunction [AO]” or “Thyroperoxidase inhibition [MIE] leading to decreased cognitive function [AO]”. In cases where the MIE is unknown or undefined, the earliest known KE in the chain (i.e., furthest upstream) should be used in lieu of the MIE and it should be made clear that the stated event is a KE and not the MIE. More help

GSK3beta inactivation leading to increased mortality via defects in developing inner ear

Short name
A short name should also be provided that succinctly summarises the information from the title. This name should not exceed 90 characters. More help
GSK3beta inactivation leads to increased mortality

Graphical Representation

A graphical summary of the AOP listing all the KEs in sequence, including the MIE (if known) and AO, and the pair-wise relationships (links or KERs) between those KEs should be provided. This is easily achieved using the standard box and arrow AOP diagram (see this page for example). The graphical summary is prepared and uploaded by the user (templates are available) and is often included as part of the proposal when AOP development projects are submitted to the OECD AOP Development Workplan. The graphical representation or AOP diagram provides a useful and concise overview of the KEs that are included in the AOP, and the sequence in which they are linked together. This can aid both the process of development, as well as review and use of the AOP (for more information please see page 19 of the Users' Handbook).If you already have a graphical representation of your AOP in electronic format, simple save it in a standard image format (e.g. jpeg, png) then click ‘Choose File’ under the “Graphical Representation” heading, which is part of the Summary of the AOP section, to select the file that you have just edited. Files must be in jpeg, jpg, gif, png, or bmp format. Click ‘Upload’ to upload the file. You should see the AOP page with the image displayed under the “Graphical Representation” heading. To remove a graphical representation file, click 'Remove' and then click 'OK.'  Your graphic should no longer be displayed on the AOP page. If you do not have a graphical representation of your AOP in electronic format, a template is available to assist you.  Under “Summary of the AOP”, under the “Graphical Representation” heading click on the link “Click to download template for graphical representation.” A Powerpoint template file should download via the default download mechanism for your browser. Click to open this file; it contains a Powerpoint template for an AOP diagram and instructions for editing and saving the diagram. Be sure to save the diagram as jpeg, jpg, gif, png, or bmp format. Once the diagram is edited to its final state, upload the image file as described above. More help


List the name and affiliation information of the individual(s)/organisation(s) that created/developed the AOP. In the context of the OECD AOP Development Workplan, this would typically be the individuals and organisation that submitted an AOP development proposal to the EAGMST. Significant contributors to the AOP should also be listed. A corresponding author with contact information may be provided here. This author does not need an account on the AOP-KB and can be distinct from the point of contact below. The list of authors will be included in any snapshot made from an AOP. More help

Vid Modic, Ziva Ramsak, Roman Li, Colette vom Berg, Anze Zupanic

Point of Contact

Indicate the point of contact for the AOP-KB entry itself. This person is responsible for managing the AOP entry in the AOP-KB and controls write access to the page by defining the contributors as described below. Clicking on the name will allow any wiki user to correspond with the point of contact via the email address associated with their user profile in the AOP-KB. This person can be the same as the corresponding author listed in the authors section but isn’t required to be. In cases where the individuals are different, the corresponding author would be the appropriate person to contact for scientific issues whereas the point of contact would be the appropriate person to contact about technical issues with the AOP-KB entry itself. Corresponding authors and the point of contact are encouraged to monitor comments on their AOPs and develop or coordinate responses as appropriate.  More help
Cataia Ives   (email point of contact)


List user names of all  authors contributing to or revising pages in the AOP-KB that are linked to the AOP description. This information is mainly used to control write access to the AOP page and is controlled by the Point of Contact.  More help
  • Vid Modic
  • Anze Zupanic
  • Cataia Ives


The status section is used to provide AOP-KB users with information concerning how actively the AOP page is being developed, what type of use or input the authors feel comfortable with given the current level of development, and whether it is part of the OECD AOP Development Workplan and has been reviewed and/or endorsed. “Author Status” is an author defined field that is designated by selecting one of several options from a drop-down menu (Table 3). The “Author Status” field should be changed by the point of contact, as appropriate, as AOP development proceeds. See page 22 of the User Handbook for definitions of selection options. More help
Author status OECD status OECD project SAAOP status
Open for citation & comment
This AOP was last modified on May 08, 2022 11:33
The date the AOP was last modified is automatically tracked by the AOP-KB. The date modified field can be used to evaluate how actively the page is under development and how recently the version within the AOP-Wiki has been updated compared to any snapshots that were generated. More help

Revision dates for related pages

Page Revision Date/Time
foxi1 expression, increased October 28, 2021 12:09
six1b expression, increased August 12, 2021 14:13
eya1 expression, inhibited October 07, 2021 12:59
Increase, Cell death September 06, 2021 07:39
altered, inner ear development August 24, 2021 07:50
Reduced, Hearing February 18, 2019 10:50
GSK3beta inactivation October 05, 2021 06:20
Repression of Gbx2 expression October 07, 2021 12:58
Increased Mortality September 08, 2021 07:07
Decrease, Population growth rate March 29, 2022 11:50
GSK3beta inactivation leads to Repression of Gbx2 expression December 12, 2021 12:23
Repression of Gbx2 expression leads to foxi1 expression, increased August 13, 2021 11:39
foxi1 expression, increased leads to six1b expression, increased October 28, 2021 12:58
six1b expression, increased leads to eya1 expression, inhibited August 13, 2021 14:44
eya1 expression, inhibited leads to Increase, Cell death August 22, 2021 15:17
Increase, Cell death leads to Altered, inner ear development August 29, 2021 09:05
Altered, inner ear development leads to Reduced, Hearing August 23, 2021 18:16
Reduced, Hearing leads to Increased Mortality December 08, 2020 03:26
Increased Mortality leads to Decrease, Population growth rate December 10, 2021 04:03
BIO (6-bromoindirubin-3’-oxime) May 29, 2019 21:19


In the abstract section, authors should provide a concise and informative summation of the AOP under development that can stand-alone from the AOP page. Abstracts should typically be 200-400 words in length (similar to an abstract for a journal article). Suggested content for the abstract includes the following: The background/purpose for initiation of the AOP’s development (if there was a specific intent) A brief description of the MIE, AO, and/or major KEs that define the pathway A short summation of the overall WoE supporting the AOP and identification of major knowledge gaps (if any) If a brief statement about how the AOP may be applied (optional). The aim is to capture the highlights of the AOP and its potential scientific and regulatory relevance More help

The focus of this AOP is on inactivation of Glycogen synthase kinase 3 beta (Gsk3b) by different chemicals which leads to defects in developing inner ear of zebrafish. Inactivation of Gsk3b leads to repressed expression of gbx2 (KE1) which consequently increases expression of two genes foxi1 (KE2) and six1b (KE3). Increase in six1b expression leads to inhibited expression of eya1 (KE4). Changes on molecular level (MIE-KE4) leads to changes at cellular level such as increased cell death in developing inner ear (KE5). Alterations in inner ear (KE6) translate to (AO) decrease in population trajectory through reduced hearing (KE7) and increased mortality (AO). An overall assessment of this AOP shows that there is low to moderate biological plausibility to suggest a qualitative link between the repression of Gsk3b expression to the KE4-cell death within developing inner ear and high evidence linking KE5 to increased mortality (AO). Currently there is not enough data for an appropriate assessment of essentiality of KEs and empirical support. KEs on molecular level have some uncertainties like foxi1 loss of function experiment resulting in no expression of six1b in otic placode  and inconsistencies between zebrafish and mouse (six1b and eya1 role in otic placode development).

Background (optional)

This optional subsection should be used to provide background information for AOP reviewers and users that is considered helpful in understanding the biology underlying the AOP and the motivation for its development. The background should NOT provide an overview of the AOP, its KEs or KERs, which are captured in more detail below. Examples of potential uses of the optional background section are listed on pages 24-25 of the User Handbook. More help

The motivation behind building the AOP was methodological. Our team has recently developed molecular causal networks for developmental cardiotoxicity and neurotoxicity in zebrafish ( These networks are highly curated, but rather large, going from adverse outcomes on the organ level upstream to wherever evidence takes us (many times finishing at what would be called MIEs). As there are many causal networks already present on the (mostly for humans and for lung conditions), we were wondering how the rich knowledge available in causal pathways could be translated to AOPs. The AOP described in this document is one such example. 

Summary of the AOP

This section is for information that describes the overall AOP. The information described in section 1 is entered on the upper portion of an AOP page within the AOP-Wiki. This is where some background information may be provided, the structure of the AOP is described, and the KEs and KERs are listed. More help


Molecular Initiating Events (MIE)
An MIE is a specialised KE that represents the beginning (point of interaction between a stressor and the biological system) of an AOP. More help
Key Events (KE)
This table summarises all of the KEs of the AOP. This table is populated in the AOP-Wiki as KEs are added to the AOP. Each table entry acts as a link to the individual KE description page.  More help
Adverse Outcomes (AO)
An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP.  More help
Sequence Type Event ID Title Short name
1 MIE 1647 GSK3beta inactivation GSK3beta inactivation
2 KE 1902 Repression of Gbx2 expression Repression of Gbx2 expression
3 KE 1903 foxi1 expression, increased foxi1 expression, increased
4 KE 1904 six1b expression, increased six1b expression, increased
5 KE 1905 eya1 expression, inhibited eya1 expression, inhibited
6 KE 1825 Increase, Cell death Increase, Cell death
7 KE 1930 altered, inner ear development Altered, inner ear development
8 KE 1008 Reduced, Hearing Reduced, Hearing
9 AO 351 Increased Mortality Increased Mortality
AO 360 Decrease, Population growth rate Decrease, Population growth rate

Relationships Between Two Key Events (Including MIEs and AOs)

This table summarises all of the KERs of the AOP and is populated in the AOP-Wiki as KERs are added to the AOP. Each table entry acts as a link to the individual KER description page.To add a key event relationship click on either Add relationship: events adjacent in sequence or Add relationship: events non-adjacent in sequence.For example, if the intended sequence of KEs for the AOP is [KE1 > KE2 > KE3 > KE4]; relationships between KE1 and KE2; KE2 and KE3; and KE3 and KE4 would be defined using the add relationship: events adjacent in sequence button.  Relationships between KE1 and KE3; KE2 and KE4; or KE1 and KE4, for example, should be created using the add relationship: events non-adjacent button. This helps to both organize the table with regard to which KERs define the main sequence of KEs and those that provide additional supporting evidence and aids computational analysis of AOP networks, where non-adjacent KERs can result in artifacts (see Villeneuve et al. 2018; DOI: 10.1002/etc.4124).After clicking either option, the user will be brought to a new page entitled ‘Add Relationship to AOP.’ To create a new relationship, select an upstream event and a downstream event from the drop down menus. The KER will automatically be designated as either adjacent or non-adjacent depending on the button selected. The fields “Evidence” and “Quantitative understanding” can be selected from the drop-down options at the time of creation of the relationship, or can be added later. See the Users Handbook, page 52 (Assess Evidence Supporting All KERs for guiding questions, etc.).  Click ‘Create [adjacent/non-adjacent] relationship.’  The new relationship should be listed on the AOP page under the heading “Relationships Between Two Key Events (Including MIEs and AOs)”. To edit a key event relationship, click ‘Edit’ next to the name of the relationship you wish to edit. The user will be directed to an Editing Relationship page where they can edit the Evidence, and Quantitative Understanding fields using the drop down menus. Once finished editing, click ‘Update [adjacent/non-adjacent] relationship’ to update these fields and return to the AOP page.To remove a key event relationship to an AOP page, under Summary of the AOP, next to “Relationships Between Two Key Events (Including MIEs and AOs)” click ‘Remove’ The relationship should no longer be listed on the AOP page under the heading “Relationships Between Two Key Events (Including MIEs and AOs)”. More help

Network View

The AOP-Wiki automatically generates a network view of the AOP. This network graphic is based on the information provided in the MIE, KEs, AO, KERs and WoE summary tables. The width of the edges representing the KERs is determined by its WoE confidence level, with thicker lines representing higher degrees of confidence. This network view also shows which KEs are shared with other AOPs. More help


The stressor field is a structured data field that can be used to annotate an AOP with standardised terms identifying stressors known to trigger the MIE/AOP. Most often these are chemical names selected from established chemical ontologies. However, depending on the information available, this could also refer to chemical categories (i.e., groups of chemicals with defined structural features known to trigger the MIE). It can also include non-chemical stressors such as genetic or environmental factors. Although AOPs themselves are not chemical or stressor-specific, linking to stressor terms known to be relevant to different AOPs can aid users in searching for AOPs that may be relevant to a given stressor. More help
Name Evidence Term
BIO (6-bromoindirubin-3’-oxime) High

Life Stage Applicability

Identify the life stage for which the KE is known to be applicable. More help
Life stage Evidence
During brain development High

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) can be selected. 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

Sex Applicability

The authors must select from one of the following: Male, female, mixed, asexual, third gender, hermaphrodite, or unspecific. More help

Overall Assessment of the AOP

This section addresses the relevant biological domain of applicability (i.e., in terms of taxa, sex, life stage, etc.) and WoE for the overall AOP as a basis to consider appropriate regulatory application (e.g., priority setting, testing strategies or risk assessment). The goal of the overall assessment is to provide a high level synthesis and overview of the relative confidence in the AOP and where the significant gaps or weaknesses are (if they exist). Users or readers can drill down into the finer details captured in the KE and KER descriptions, and/or associated summary tables, as appropriate to their needs.Assessment of the AOP is organised into a number of steps. Guidance on pages 59-62 of the User Handbook is available to facilitate assignment of categories of high, moderate, or low confidence for each consideration. While it is not necessary to repeat lengthy text that appears elsewhere in the AOP description (or related KE and KER descriptions), a brief explanation or rationale for the selection of high, moderate, or low confidence should be made. More help

An overall assessment of this AOP shows that there is low to moderate biological plausibility to suggest a qualitative link between the inactivation of Gsk3b to the KE4-cell death within developing inner ear and high evidence linking KE5 to increased mortality (AO). Biological plausibility is considered moderate because there is ample evidence from gain- and loss- of function experiments and knock out animal models that support the relationships between key events which are consistent with current biological knowledge, but there is mostly indirect evidence linking KEs on molecular level. KEs on molecular level have some uncertainties like foxi1 loss of function experiment resulting in no expression of six1b in otic placode (due to absence of otic placode)  and inconsistencies across species (zebrafish, mouse). The evidence for essentiality of the KEs is mostly missing therefore the overall assessment of essentiality is low. The same goes for empirical support, currently there is no evidence for empirical support. Additional studies are needed to obtain data for empirical support, therefore, the empirical support of KERs is considered is low.

Domain of Applicability

The relevant biological domain(s) of applicability in terms of sex, life-stage, taxa, and other aspects of biological context are defined in this section. Biological domain of applicability is informed by the “Description” and “Biological Domain of Applicability” sections of each KE and KER description (see sections 2G and 3E for details). In essence the taxa/life-stage/sex applicability is defined based on the groups of organisms for which the measurements represented by the KEs can feasibly be measured and the functional and regulatory relationships represented by the KERs are operative.The relevant biological domain of applicability of the AOP as a whole will nearly always be defined based on the most narrowly restricted of its KEs and KERs. For example, if most of the KEs apply to either sex, but one is relevant to females only, the biological domain of applicability of the AOP as a whole would be limited to females. While much of the detail defining the domain of applicability may be found in the individual KE and KER descriptions, the rationale for defining the relevant biological domain of applicability of the overall AOP should be briefly summarised on the AOP page. More help

Life stage: The current AOP is applicable from 2-8 cell stage (1,25 hpf; start of Gsk3b expression in zebrafish) (Valenti, 2015) up to 96 hpf wich is the expression limit of six1b in the developing inner ear (Webb & Shirey, 2003).

Taxonomic: This AOP is  based on experimental evidence from studies on zebrafish, but is potentially also relevant to other vertebrates, because of conservation of all involved key events  (Wnt signalling-Gsk3b, Gbx2, Eya1). But there are certain differences especially between zebrafish and mouse. Foxi1 gene is critical for zebrafish otic induction (Solomon et al., 2003), while it is not essential for this process in mice (Hulander et al., 2003). Interactions between Six1b and other members ofthe Pax–Six–Eya–Dach gene network, such as Eya1, also seem to differ between mouse and zebrafish (Li et al., 2003; Zheng et al., 2003).

Sex: Sex differences are typically not investigated in tests using early life stages of zebrafish and it is currently unclear whether sex-related differences are important in this AOP.

Essentiality of the Key Events

An important aspect of assessing an AOP is evaluating the essentiality of its KEs. The essentiality of KEs can only be assessed relative to the impact of manipulation of a given KE (e.g., experimentally blocking or exacerbating the event) on the downstream sequence of KEs defined for the AOP. Consequently evidence supporting essentiality is assembled on the AOP page, rather than on the independent KE pages that are meant to stand-alone as modular units without reference to other KEs in the sequence.The nature of experimental evidence that is relevant to assessing essentiality relates to the impact on downstream KEs and the AO if upstream KEs are prevented or modified. This includes: Direct evidence: directly measured experimental support that blocking or preventing a KE prevents or impacts downstream KEs in the pathway in the expected fashion. Indirect evidence: evidence that modulation or attenuation in the magnitude of impact on a specific KE (increased effect or decreased effect) is associated with corresponding changes (increases or decreases) in the magnitude or frequency of one or more downstream KEs.When assembling the support for essentiality of the KEs, authors should organise relevant data in a tabular format. The objective is to summarise briefly the nature and numbers of investigations in which the essentiality of KEs has been experimentally explored either directly or indirectly. See pages 50-51 in the User Handbook for further definitions and clarifications.  More help
Support for Essentiality of KEs

Defining Question: Are downstream KEs and/or the AO prevented if an upstream KE is blocked?

  • High (Strong): Direct evidence from specifically designed experimental studies illustrating essentiality for at least one of the important KEs (e.g. stop/reversibility studies, antagonism, knock out models, etc.).
  • Moderate: Indirect evidence that sufficient modification of an expected modulating factor attenuates or augments a KE leading to increase in KE down or AO.
  • Low (Weak): No or contradictory experimental evidence of the essentiality of any of the KEs.
MIE: Gsk3b inactivation Low: No experimental evidence of essentiality.
KE1: Repression of gbx2 expression Low: No experimental evidence of essentiality.
KE2: Increased foxi1 expression High: When foxi1 is knock down no expression of six1b is detected in otocyst (Bricaud and Collazo, 2006).
KE3: Increased six1b expression Moderate: Six1b gain/loss-of-function experiment results indicate that in both cases normal development of inner ear is affected (KE5) (Bricaud and Collazo, 2006).
KE4: Inhibited  eya1 expression Low: No experimental evidence of essentiality.
KE5: Increased cell death High: One of key players in normal development of sensory organs (KE6) (Whitfield et al., 2002; Kozlowski et al., 2005).
KE6: Altered inner ear development Low: No experimental evidence of essentiality.
KE7: Reduced hearing Moderate: One of the factors that are responsible for higher rate of mortality in fish (KE8) (Kasumyan, 2009).
AO: Increased mortality High: Inability to perceive the environment leads to increase in mortality (Besson et al., 2020).
AO: Decrease of population trajectory High: decrease in population trajectory is an imminent result of increased mortality (Rearick et al., 2018).

Evidence Assessment

The biological plausibility, empirical support, and quantitative understanding from each KER in an AOP are assessed together.  Biological plausibility of each of the KERs in the AOP is the most influential consideration in assessing WoE or degree of confidence in an overall hypothesised AOP for potential regulatory application (Meek et al., 2014; 2014a). Empirical support entails consideration of experimental data in terms of the associations between KEs – namely dose-response concordance and temporal relationships between and across multiple KEs. It is examined most often in studies of dose-response/incidence and temporal relationships for stressors that impact the pathway. While less influential than biological plausibility of the KERs and essentiality of the KEs, empirical support can increase confidence in the relationships included in an AOP. For clarification on how to rate the given empirical support for a KER, as well as examples, see pages 53- 55 of the User Handbook.  More help
Support for Biological Plausibility of KERs

Defining Question: Is there a mechanistic relationship between KEup and KEdown consistent with established biological knowledge?

  • High (Strong): Extensive understanding of the KER based on extensive previous documentation and broad acceptance.
  • Moderate: KER is plausible based on analogy to accepted biological relationships, but scientific understanding is incomplete.
  • Low (Weak): Empirical support for association between KEs, but the structural or functional relationship between them is not understood.
KER1: Gsk3b inactivation leads to repression of gbx2 expression High: There is extensive evidence linking inhibition of Gsk3b to activation of canonical Wnt pathway for which Gbx2 is representative marker.
KER2: Repression of gbx2 expression leads to increased foxi1 expression Moderate: Extensive evidence that Gbx2 represses many developmental regulatory genes such as foxi1, but multifunctional nature of Gbx2 is still unknown.
KER3: Increased foxi1 expression leads to increased six1b expression Low: Relationship was confirmed with loss-of-function experiment, but the connection could be secondary to the overall absence of otic placode.
KER4: Increased six1b expression leads to inhibited eya1 expression Low: Mutual regulation and interactions of both entities have not yet been well researched and described. Inconsistencies in zebrafish and mouse models.
KER5: Inhibited eya1 expression leads to increased cell death High: Extensive evidence of relationship in vertebrate models.
KER6: Increased cell death leads to altered inner ear development High: Extensive understanding that inner ear development depends on correct regulation of cell death in precursor cells and tissues.
KER7: Altered inner ear development leads to reduced hearing High: Extensive understanding of defects in the development of inner ear and outcomes suggestive of deafness.
KER8: Reduced hearing leads to increased mortality High: Extensive understanding that defective hearing decreases survival in natural setting.
KER9: Increased mortality leads to decrease of population trajectory High: Extensive understanding that increased mortality on individual level decreases population trajectory.

Empirical support: Currently there is no sufficient evidence to estimate the weight of the evidence of empirical support for KERs in this AOP. Further more specific research on the relationships between the entities involved in the AOP is needed.

Quantitative Understanding

Some proof of concept examples to address the WoE considerations for AOPs quantitatively have recently been developed, based on the rank ordering of the relevant Bradford Hill considerations (i.e., biological plausibility, essentiality and empirical support) (Becker et al., 2017; Becker et al, 2015; Collier et al., 2016). Suggested quantitation of the various elements is expert derived, without collective consideration currently of appropriate reporting templates or formal expert engagement. Though not essential, developers may wish to assign comparative quantitative values to the extent of the supporting data based on the three critical Bradford Hill considerations for AOPs, as a basis to contribute to collective experience.Specific attention is also given to how precisely and accurately one can potentially predict an impact on KEdownstream based on some measurement of KEupstream. This is captured in the form of quantitative understanding calls for each KER. See pages 55-56 of the User Handbook for a review of quantitative understanding for KER's. More help

Data to support the quantitative understanding of this AOP is currently lacking.

Considerations for Potential Applications of the AOP (optional)

At their discretion, the developer may include in this section discussion of the potential applications of an AOP to support regulatory decision-making. This may include, for example, possible utility for test guideline development or refinement, development of integrated testing and assessment approaches, development of (Q)SARs / or chemical profilers to facilitate the grouping of chemicals for subsequent read-across, screening level hazard assessments or even risk assessment. While it is challenging to foresee all potential regulatory application of AOPs and any application will ultimately lie within the purview of regulatory agencies, potential applications may be apparent as the AOP is being developed, particularly if it was initiated with a particular application in mind. This optional section is intended to provide the developer with an opportunity to suggest potential regulatory applications and describe his or her rationale.To edit the “Considerations for Potential Applications of the AOP” section, on an AOP page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing AOP.” Scroll down to the “Considerations for Potential Applications of the AOP” section, where a text entry box allows you to submit text. In the upper right hand menu, click ‘Update AOP’ to save your changes and return to the AOP page or 'Update and continue' to continue editing AOP text sections.  The new text should appear under the “Considerations for Potential Applications of the AOP” section on the AOP page. More help


List the bibliographic references to original papers, books or other documents used to support the AOP. More help

Besson, M. et. al. 2020. „Anthropogenic stressors impact fish sensory development and survival via thyroid disruption“. Nature Communications 2020 11:1 11(1): 1–10.

Bricaud, O., Leslie, A. C., & Gonda, S. (2006). Development/Plasticity/Repair The Transcription Factor six1 Inhibits Neuronal and Promotes Hair Cell Fate in the Developing Zebrafish (Danio rerio) Inner Ear. Journal of Neuroscience, 26(41), 10438–10451.

Hulander, M., Kiernan, A., Blomqvist, S., Carlsson, P., Samuelsson, E., Johansson, B., Steel, K., & Enerbäck, S. (2003). Lack of pendrin expression leads to deafness and expansion of the endolymphatic compartment in inner ears of Foxi1null mutant mice 2013. Development, 130, 2013–2025.

Kasumyan, A. O. 2009. „Acoustic signaling in fish“. Journal of Ichthyology 2009 49:11 49(11): 963–1020.

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.

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.

Rearick, Daniel C., Jessica Ward, Paul Venturelli and Heiko Schoenfuss. 2018. „Environmental oestrogens cause predation-induced population decline in a freshwater fish“. Royal Society Open Science 5(10).

Sklirou, A. D. et al. (2017) ‘6-bromo-indirubin-3′-oxime (6BIO), a Glycogen synthase kinase-3β inhibitor, activates cytoprotective cellular modules and suppresses cellular senescence-mediated biomolecular damage in human fibroblasts’, Sci Rep, 7, p. 11713. doi: 10.1038/s41598-017-11662-7.

Solomon, K. S., Kudoh, T., Dawid, I. B., & Fritz, A. (2003). Zebrafish foxi1 mediates otic placode formation and jaw development. Development, 130(5), 929–940.

Valenti, Fabio et al. 2015. „The Increase in Maternal Expression of axin1 and axin2 Contribute to the Zebrafish Mutant Ichabod Ventralized Phenotype“. Journal of Cellular Biochemistry 116(3): 418–30.

Wang, Z. et al. (2018) ‘The role of gastrulation brain homeobox 2 (gbx2) in the development of the ventral telencephalon in zebrafish embryos’, Differentiation, 99(September 2017), pp. 28–40. doi: 10.1016/j.diff.2017.12.005.

Webb, J. F., & Shirey, J. E. (2003). Postembryonic Development of the Cranial Lateral Line Canals and Neuromasts in Zebrafish. Developmental Dynamics, 228(3), 370–385.

Whitfield, T. T., Riley, B. B., Chiang, M. Y., & Phillips, B. (2002). Development of the zebrafish inner ear. Developmental Dynamics, 223(4), 427–458.

Zheng, W., Huang, L., Wei, Z.-B., Silvius, D., Tang, B., & Pin-Xian, X. (2003). The role of Six1 in mammalian auditory system development. Development, 130, 3989–4000.