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Event: 1902

Key Event Title

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

Repression of Gbx2 expression

Short name

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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

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

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

During vertebrate brain development, the gastrulation brain homeobox 2 gene (gbx2) is expressed in the forebrain (Z. Wang et al., 2018). The genes encoding the Gbx-type homeodomain transcription factors have been identified in a variety of vertebrates, and are primarily implicated in the regulation of various aspects of vertebrate brain development (Nakayama et al., 2017). Gbx2 exhibits DNA-binding transcription factor activity, RNA polymerase II-specific. Involved in cerebellum development; iridophore differentiation; and telencephalon regionalization. Predicted to localize to nucleus. Is expressed in several structures, including midbrain hindbrain boundary neural keel; midbrain hindbrain boundary neural rod; midbrain neural rod; nervous system; and presumptive rhombomere 1. Orthologous to human GBX2 (gastrulation brain homeobox 2) (ZFIN Gene: Gbx2, n.d.). Gbx2 is one of the key downstream markers of FGF and WNT signaling (Wang et al., 2018), representative marker of anteroposterior (AP) axis patterning and midbrain specification (Kim et al., 2018).

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

Repression 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. Measuring changes in Gbx2 expression are described in detail in (Rhinn et al., 2003; Nakayama et al., 2017; Wang et al., 2018).

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

The gastrulation brain homebox (Gbx) group of transcription factor genes, composed of two genes, gbx1 and gbx2, in vertebrates, is also present in invertebrates (Chiang et al., 1995), and can be regarded as widely conserved among animals (Wang et al., 2018). Gbx2 functions in a variety of developmental processes after midbrain-hindbrain boundary (MHB) establishment. (Burroughs-Garcia et al., 2011) data demonstrate that the role of gbx2 in anterior hindbrain development is functionally conserved between zebrafish and mice. This gene was shown to be required for neural crest (NC) formation in mice (B. Li et al., 2009; Roeseler et al., 2012). In Xenopus gbx2 is the earliest factor for specifying neural crest (NC) cells, and that gbx2 is directly regulated by NC inducing signaling pathways, such as Wnt/β-catenin signaling (Li et al., 2009).

References

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

Chiang, C., Young, K. E., & Beachy, P. A. (1995). Control of Drosophila tracheal branching by the novel homeodomain gene unplugged, a regulatory target for genes of the bithorax complex. Development, 121(11), 3901–3912.

Li, B., Kuriyama, S., Moreno, M., & Mayor, R. (2009). The posteriorizing gene Gbx2 is a direct target of Wnt signalling and the earliest factor in neural crest induction. Development, 136(19), 3267–3278. https://doi.org/10.1242/dev.036954

Luu, B., Ellisor, D., & Zervas, M. (2011). The Lineage Contribution and Role of Gbx2 in Spinal Cord Development. PLoS ONE, 6. https://doi.org/10.1371/journal.pone.0020940

Nakayama, Y., Inomata, C., Yuikawa, T., Tsuda, S., & Yamasu, K. (2017). Comprehensive analysis of target genes in zebrafish embryos reveals gbx2 involvement in neurogenesis. Developmental Biology, 430(1), 237–248. https://doi.org/10.1016/j.ydbio.2017.07.015

Rhinn, M. et al. (2003) ‘Cloning, expression and relationship of zebrafish gbx1 and gbx2 genes to Fgf signaling’, Mechanisms of Development, 120(8), pp. 919–936. doi: 10.1016/S0925-4773(03)00135-7.

Roeseler, D. A., Sachdev, S., Buckley, D. M., Joshi, T., & Wu, D. K. (2012). Elongation Factor 1 alpha1 and Genes Associated with Usher Syndromes Are Downstream Targets of GBX2. PLoS ONE, 7(11), 47366. https://doi.org/10.1371/journal.pone.0047366

Wang, Z., Nakayama, Y., Tsuda, S., & Yamasu, K. (2018). The role of gastrulation brain homeobox 2 (gbx2) in the development of the ventral telencephalon in zebrafish embryos. Differentiation, 99(December 2017), 28–40. https://doi.org/10.1016/j.diff.2017.12.005

ZFIN Gene: gbx2. (n.d.). Retrieved April 12, 2021, from https://zfin.org/ZDB-GENE-020509-2