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Event: 1904

Key Event Title

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

six1b expression, increased

Short name
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six1b 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

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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

Life Stages

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Sex Applicability

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Key Event Description

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Six1b is predicted to have DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in several processes, including muscle organ development; nervous system development; and regulation of skeletal muscle cell proliferation. Human ortholog(s) of this gene implicated in autosomal dominant nonsyndromic deafness; branchiootorenal syndrome; and nephroblastoma. Orthologous to human SIX1 (SIX homeobox 1) (ZFIN Gene: Six1b, n.d.).

Six1b is a Member of the Pax–Six1b–Eya–Dach ( paired box–sine oculis homeobox–eyes absent– dachshund) gene regulatory network, involved in the development of numerous organs and tissues (Bessarab et al., 2004; Bricaud et al., 2006). It has been proposed to play an important role in inner ear development (Baker & Bronner-Fraser, 2001; Whitfield et al., 2002). Six1b expression appears to be regulated by pax2b and also by foxi1 (forkhead box I1) as expected for an early inducer of the otic placode (Bricaud et al., 2006).

Six1b promotes hair cell fate and, conversely, inhibits neuronal fate by differentially affecting cell proliferation and cell death in these lineages. Gain/loss-of-function experiment results indicate that, when six1 is overexpressed, not only are fewer neural progenitors formed but many of these progenitors do not go on to differentiate into neurons (Bricaud et al., 2006).

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 for vertebrates ((Brodbeck & Englert, 2004; Heanue et al., 1999; Li et al., 2003; Wawersik & Maas, 2000) and Drosophila (Bui et al., 2000).

References

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

Baker, C. V. H., & Bronner-Fraser, M. (2001). Vertebrate cranial placodes. I. Embryonic induction. Developmental Biology, 232(1), 1–61. https://doi.org/10.1006/dbio.2001.0156

Bessarab, D. A., Chong, S., & Korzh, V. (2004). Expression of Zebrafish six1 During Sensory Organ Development and Myogenesis. June, 781–786. https://doi.org/10.1002/dvdy.20093

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. https://doi.org/10.1523/JNEUROSCI.1025-06.2006

Brodbeck, S., & Englert, C. (2004). Genetic determination of nephrogenesis: The Pax/Eya/Six gene network. Pediatric Nephrology, 19(3), 249–255. https://doi.org/10.1007/s00467-003-1374-z

Heanue, T. A., Reshef, R., Davis, R. J., Mardon, G., Oliver, G., Tomarev, S., Lassar, A. B., & Tabin, C. J. (1999). Synergistic regulation of vertebrate muscle development by Dach2, Eya2, and Six1, homologs of genes required for Drosophila eye formation. www.genesdev.org

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

Wawersik, S., & Maas, R. L. (2000). Vertebrate eye development as modeled in Drosophila. In Human Molecular Genetics (Vol. 9, Issue 6). http://hgu.mrc.ac.uk/Softdata/PAX6/

Whitfield, T. T., Riley, B. B., Chiang, M. Y., & Phillips, B. (2002). Development of the zebrafish inner ear. Developmental Dynamics, 223(4), 427–458. https://doi.org/10.1002/dvdy.10073

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: six1b. (n.d.). Retrieved April 12, 2021, from https://zfin.org/ZDB-GENE-040426-230