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Relationship: 2437
Title
A descriptive phrase which clearly defines the two KEs being considered and the sequential relationship between them (i.e., which is upstream, and which is downstream).
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foxi1 expression, increased leads to six1b expression, increased
Upstream event
The causing Key Event (KE) in a Key Event Relationship (KER).
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Downstream event
The responding Key Event (KE) in a Key Event Relationship (KER).
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The utility of AOPs for regulatory application is defined, to a large extent, by the confidence and precision with which they facilitate extrapolation of data measured at low levels of biological organisation to predicted outcomes at higher levels of organisation and the extent to which they can link biological effect measurements to their specific causes.Within the AOP framework, the predictive relationships that facilitate extrapolation are represented by the KERs. Consequently, the overall WoE for an AOP is a reflection in part, of the level of confidence in the underlying series of KERs it encompasses. Therefore, describing the KERs in an AOP involves assembling and organising the types of information and evidence that defines the scientific basis for inferring the probable change in, or state of, a downstream KE from the known or measured state of an upstream KE.
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AOPs Referencing Relationship
| AOP Name | Adjacency | Weight of Evidence | Quantitative Understanding | Point of Contact | Author Status | OECD Status |
|---|---|---|---|---|---|---|
| GSK3beta inactivation leading to increased mortality via defects in developing inner ear | adjacent | Low | Low | 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 KER.In general, this will be dictated by the more restrictive of the two KEs being linked together by the KER.
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| Term | Scientific Term | Evidence | Link |
|---|---|---|---|
| zebrafish | Danio rerio | High | NCBI |
Sex Applicability
An indication of the the relevant sex for this KER.
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| Sex | Evidence |
|---|---|
| Unspecific | High |
Life Stage Applicability
An indication of the the relevant life stage(s) for this KER.
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| Term | Evidence |
|---|---|
| Embryo | High |
Provides a concise overview of the information given below as well as addressing details that aren’t inherent in the description of the KEs themselves.
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Increased foxi1 expression leads to increased six1b expression.
Include a description of the approach for identification and assembly of the evidence base for the KER. For evidence identification, include, for example, a description of the sources and dates of information consulted including expert knowledge, databases searched and associated search terms/strings. Include also a description of study screening criteria and methodology, study quality assessment considerations, the data extraction strategy and links to any repositories/databases of relevant references.Tabular summaries and links to relevant supporting documentation are encouraged, wherever possible.
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| ID | Experimental Design | Species | Upstream Observation | Downstream Observation | Citation (first author, year) | Notes |
|---|
Addresses the scientific evidence supporting KERs in an AOP setting the stage for overall assessment of the AOP.
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| Title | First Author | Biological Plausibility |
Dose Concordance |
Temporal Concordance |
Incidence Concordance |
|---|
Biological Plausibility
Dose Concordance Evidence
Temporal Concordance Evidence
Incidence Concordance Evidence
Uncertainties and Inconsistencies
Addresses inconsistencies or uncertainties in the relationship including the identification of experimental details that may explain apparent deviations from the expected patterns of concordance.
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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).
This table captures specific information on the MF, its properties, how it affects the KER and respective references.1.) What is the modulating factor? Name the factor for which solid evidence exists that it influences this KER. Examples: age, sex, genotype, diet 2.) Details of this modulating factor. Specify which features of this MF are relevant for this KER. Examples: a specific age range or a specific biological age (defined by...); a specific gene mutation or variant, a specific nutrient (deficit or surplus); a sex-specific homone; a certain threshold value (e.g. serum levels of a chemical above...) 3.) Description of how this modulating factor affects this KER. Describe the provable modification of the KER (also quantitatively, if known). Examples: increase or decrease of the magnitude of effect (by a factor of...); change of the time-course of the effect (onset delay by...); alteration of the probability of the effect; increase or decrease of the sensitivity of the downstream effect (by a factor of...) 4.) Provision of supporting scientific evidence for an effect of this MF on this KER. Give a list of references.
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No Data.
Captures information that helps to define how much change in the upstream KE, and/or for how long, is needed to elicit a detectable and defined change in the downstream KE.
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No Data.
Response-response Relationship
Provides sources of data that define the response-response relationships between the KEs.
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No Data.
Time-scale
Information regarding the approximate time-scale of the changes in KEdownstream relative to changes in KEupstream (i.e., do effects on KEdownstream lag those on KEupstream by seconds, minutes, hours, or days?).
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- Expression of zebrafish six1b in the Inner Ear and Neuromasts: Expression of six1b was observed in the developing inner ear and neuromasts of the lateral line until 96 hpf, the latest stage analyzed in this study. Transcripts of six1b were detected in all five sensory patches of the inner ear as well as in the semicircular canals. Detected first at 48 hpf, six1b expression in neuromasts of the midbody lateral line reached its peak at 72 hpf with stronger staining at the basal region of the neuromast, where bodies of hair cells are localized (Webb & Shirey, 2003).
- Expression of zebrafish six1b in Muscles: Since the beginning of segmentation six1b was expressed in the somites. At 72 hpf, the expression of six1b became more pronounced in the ventral somites with stronger staining in the most ventral cells. It continued in the pectoral fin and ventral abdomen muscle. Six1b expression was also found in the muscles of the eye and the lower jaw. (Bricaud et al., 2006).
- Temporal changes in gene expression and the emergence of sensory placode progenitors. As development proceeds gene expression domains sharpen through mutually repressive interactions; in the head region, the neural crest and placode precursor specific transcripts begin to be expressed at early neurula stages. Initially their boundaries are fuzzy, but gene expression resolves to distinct domains by late neurula (black dashed lines). NP: neural plate; NC: neural crest; PPR: preplacodal region; Epi: future epidermis. Right: diagram of an embryo at early neurula stages; dashed lines indicate the medial boundaries of non-neural transcripts (Lleras-Forero & Streit, 2012).
Known Feedforward/Feedback loops influencing this KER
Define whether there are known positive or negative feedback mechanisms involved and what is understood about their time-course and homeostatic limits.
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No Data.
A free-text section of the KER description that the developers can use to explain their rationale for the taxonomic, life stage, or sex applicability structured terms.
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Data was provided for zebrafish (Bricaud et al., 2006; Lleras-Forero & Streit, 2012), mice and chick (Hulander et al., 2003; Lleras-Forero & Streit, 2012)