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Event: 1903

Key Event Title

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

foxi1 expression, increased

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
foxi1 expression, increased
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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 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

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Sex Applicability

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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

Foxi1 exhibits DNA-binding transcription factor activity. Involved in several processes, including animal organ development; epidermal cell fate specification; and neuron development. Predicted to localize to nucleus. Is expressed in several structures, including ectoderm; epibranchial ganglion; head; neural crest; and neurogenic field. Human ortholog(s) of this gene implicated in autosomal recessive nonsyndromic deafness. Orthologous to human FOXI1 (forkhead box I1) (ZFIN Gene: Foxi1, n.d.). The zebrafish Foxi1 protein shares 52% identity with Xenopus FoxI1c and 40% with human FOXI1; the forkhead domains are 95% and 94% identical, respectively (Solomon et al., 2003).

Zebrafish Foxi1 is expressed in nonneural ectoderm. Based on double in situ labeling with otx2, the anterior-most region of foxi1 expression lies just posterior to the midbrain hindbrain boundary. At the three-somite stage, the two domains of foxi1 expression become more compact, but are still located in approximately the same position lateral to the hindbrain (Solomon et al., 2003).

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

Foxi I class genes have been described in zebrafish (Hans et al., 2004; Solomon et al., 2003),  humans (Larsson et al., 1995; Pierrou et al., 1994), mouse (Hulander et al., 1998; Overdier et al., 1997), rat (Clevidence et al., 1993) and Xenopus (Lef et al., 1994, 1996). However, it is unclear whether zebrafish foxi1 is orthologous to any one of these genes. The Xenopus FoxI1c (Lef et al., 1996), FoxI1a and FoxI1b genes (Lef et al., 1994) share the highest degree of sequence conservation with the zebrafish gene. The expression pattern of the two Xenopus pseudoallelic variants FoxI1a/b does not suggest functional similarity to zebrafish foxi1. Of the three Xenopus FoxI genes, FoxI1c (XFD-10) is most similar to foxi1 in sequence. However, Xenopus FoxI1c was reported to be expressed in the neuroectoderm and somites but not in the otic placode, unlike the pattern for foxi1 reported in (Lef et al., 1996). (Pohl et al., 2002) report provides a more detailed description of Xenopus FoxI1c, which suggests that this gene is expressed in preplacodal tissue and the branchial arches, similar to observations for zebrafish foxi1. Thus, it appears probable that Xenopus FoxI1c represents the ortholog of zebrafish foxi1 (Solomon et al., 2003).

References

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

Clevidence, D. E., Overdier, D. G., Taot, W., Qian, X., Pani, L., Lait, E., & Costa, R. H. (1993). Identification of nine tissue-specific transcription factors of the hepatocyte nuclear factor 3/forkhead DNA-binding-domain family (tissue-specific transcription factors/gene family/differentiation). In Proc. Natl. Acad. Sci. USA (Vol. 90).

Hulander, M., Wurst, W., Carlsson, P., & Enerbäck, S. (1998). The winged helix transcription factor FKh10 is required for normal development of the inner ear. Nature Genetics, 20(4), 374–376. https://doi.org/10.1038/3850

Larsson, C., Hellqvist, M., Pierrou, S., White, I., Enerback, S. and, & Carlsson, P. (1995). Chromosomal Localization of Six Human Forkhead Genes, freac-1 (FKHL5), -3 (FKHL7), -4 (FKHL8), -5 (FKHL9), -6 (FKHL10), and -8 (FKHL12). Genomics, 30, 464–469.

Lef, J., Clement, J. H., Oschwald, R., Köster, M., & Knöchel, W. (1994). Spatial and temporal transcription patterns of the forkhead related XFD-2/XFD-2′ genes in Xenopus laevis embryos. Mechanisms of Development, 45(2), 117–126. https://doi.org/10.1016/0925-4773(94)90025-6

Lef, J., Dege, P., Scheucher, M., Forsbach-Birk, V., Clement, J. H., & Knöchel, W. (1996). A fork head related multigene family is transcribed in Xenopus laevis embryos. International Journal of Developmental Biology, 40(1), 245–253. https://doi.org/10.1387/ijdb.8735935

Overdier, D. G., Ye, H., Peterson, R. S., Clevidence, D. E., & Costa, R. H. (1997). The Winged Helix Transcriptional Activator HFH-3 Is Expressed in the Distal Tubules of Embryonic and Adult Mouse Kidney*. In THE JOURNAL OF BIOLOGICAL CHEMISTRY (Vol. 272, Issue 21). https://doi.org/10.1074/jbc.272.21.13725

Pierrou, S., Hellqvist, M., Samuelsson, L., Enerbäck, S., & Carlsson, P. (1994). Cloning and characterization of seven human forkhead proteins: Binding site specificity and DNA bending. EMBO Journal, 13(20), 5002–5012. https://doi.org/10.1002/j.1460-2075.1994.tb06827.x

Pohl, B. S., Knöchel, S., Dillinger, K., & Knöchel, W. (2002). Sequence and expression of FoxB2 (XFD-5) and FoxI1c (XFD-10) in Xenopus embryogenesis. Mechanisms of Development, 117(1–2), 283–287. https://doi.org/10.1016/S0925-4773(02)00184-3

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. https://doi.org/10.1242/dev.00308

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

         ZFIN Gene: foxi1. (n.d.). Retrieved April 12, 2021, from https://zfin.org/ZDB-GENE-030505-1