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Key Event Title
Decrease, Sonic Hedgehog second messenger production
|Level of Biological Organization|
Key Event Components
|second-messenger-mediated signaling||sonic hedgehog protein||decreased|
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|Anatagonsim SMO leads to OFC||KeyEvent||Arthur Author (send email)||Under development: Not open for comment. Do not cite|
|Decrease, GLI1/2 target gene expression leads to OFC||KeyEvent||Agnes Aggy (send email)||Under development: Not open for comment. Do not cite|
Key Event Description
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
- 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
- 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)
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.