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Event: 2043

Key Event Title

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

Decrease, Sonic Hedgehog second messenger production

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

Decrease, SHH second messenger production

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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Cellular

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

Cell term
cell

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

Process	Object	Action
second-messenger-mediated signaling	sonic hedgehog protein	decreased

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
Antagonism SMO leads to OFC	KeyEvent	Jacob Reynolds (send email)	Under development: Not open for comment. Do not cite	Under Development
Decrease, GLI1/2 target gene expression leads to OFC	KeyEvent	Jacob Reynolds (send email)	Under development: Not open for comment. Do not cite	Under Development
Decrease, cholesterol synthesis leads to OFC	KeyEvent	Jacob Reynolds (send email)	Under development: Not open for comment. Do not cite	Under Development

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
Vertebrates	Vertebrates		NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
Embryo

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Unspecific

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 normal Sonic Hedgehog (SHH) signaling, GLI target gene expression regulates several other signaling pathways. Expression of FOXF1 and FOXL1 upregulate BMP4, BMP 2, and FGF10 in the mesenchyme (Katoh and Katoh 2009, Lan and Jiang 2009). Induction of FGF10 in the mesenchyme is able to induce SHH in the adjacent epithelium via a positive feedback loop with FGFR2 (Cobourne and Green 2012). SHH signaling also upregulates BCL2 and CFLAR to promote cell survival (Katoh and Katoh 2009).

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

Changes in gene expression can be measured using serial analysis of gene expression (SAGE), rapid analysis of gene expression (RAGE), RT-PCR, Northern/Southern blotting, differential display, and DNA microarray assay (Kirby, Heath et al. 2007).
RNA in situ hybridization can be used to determine sites of gene expression (Nouri-Aria 2008, Abler, Mansour et al. 2009)
Antibody staining of tissue sections can be used to determine location and amounts of BMP4, BMP2, FGF10

Domain of Applicability

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

Sex- Secondary messenger production of the SHH pathway is present in both male and females and differences in gene expression has not been demonstrated.
Life stages- The Hedgehog pathway is a major pathway in embryonic development.
Taxonomic-HH signalling, and its’ secondary messenger production is present in vertebrates and some invertebrates including flies (Denef, Neubüser et al. 2000, Huangfu and Anderson 2005)

References

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

Abler, L. L., S. L. Mansour and X. Sun (2009). "Conditional gene inactivation reveals roles for Fgf10 and Fgfr2 in establishing a normal pattern of epithelial branching in the mouse lung." Dev Dyn 238(8): 1999-2013.

Cobourne, M. T. and J. B. Green (2012). "Hedgehog signalling in development of the secondary palate." Front Oral Biol 16: 52-59.

Denef, N., D. Neubüser, L. Perez and S. M. Cohen (2000). "Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened." Cell 102(4): 521-531.

Huangfu, D. and K. V. Anderson (2005). "Cilia and Hedgehog responsiveness in the mouse." Proc Natl Acad Sci U S A 102(32): 11325-11330.

Katoh, Y. and M. Katoh (2009). "Hedgehog target genes: mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation." Curr Mol Med 9(7): 873-886.

Kirby, J., P. R. Heath, P. J. Shaw and F. C. Hamdy (2007). Gene Expression Assays. Advances in Clinical Chemistry, Elsevier. 44: 247-292.

Lan, Y. and R. Jiang (2009). "Sonic hedgehog signaling regulates reciprocal epithelial-mesenchymal interactions controlling palatal outgrowth." Development 136(8): 1387-1396.

Nouri-Aria, K. T. (2008). "In situ Hybridization." Methods Mol Med 138: 331-347.