Hedgehog: functions and mechanisms - PubMed (original) (raw)
Review
. 2008 Sep 15;22(18):2454-72.
doi: 10.1101/gad.1693608.
Affiliations
- PMID: 18794343
- DOI: 10.1101/gad.1693608
Free article
Review
Hedgehog: functions and mechanisms
Markku Varjosalo et al. Genes Dev. 2008.
Free article
Abstract
The Hedgehog (Hh) family of proteins control cell growth, survival, and fate, and pattern almost every aspect of the vertebrate body plan. The use of a single morphogen for such a wide variety of functions is possible because cellular responses to Hh depend on the type of responding cell, the dose of Hh received, and the time cells are exposed to Hh. The Hh gradient is shaped by several proteins that are specifically required for Hh processing, secretion, and transport through tissues. The mechanism of cellular response, in turn, incorporates multiple feedback loops that fine-tune the level of signal sensed by the responding cells. Germline mutations that subtly affect Hh pathway activity are associated with developmental disorders, whereas somatic mutations activating the pathway have been linked to multiple forms of human cancer. This review focuses broadly on our current understanding of Hh signaling, from mechanisms of action to cellular and developmental functions. In addition, we review the role of Hh in the pathogenesis of human disease and the possibilities for therapeutic intervention.
Similar articles
- Mechanisms of Hedgehog gradient formation and interpretation.
Torroja C, Gorfinkiel N, Guerrero I. Torroja C, et al. J Neurobiol. 2005 Sep 15;64(4):334-56. doi: 10.1002/neu.20168. J Neurobiol. 2005. PMID: 16041759 Review. - The long-range activity of Hedgehog is regulated in the apical extracellular space by the glypican Dally and the hydrolase Notum.
Ayers KL, Gallet A, Staccini-Lavenant L, Thérond PP. Ayers KL, et al. Dev Cell. 2010 Apr 20;18(4):605-20. doi: 10.1016/j.devcel.2010.02.015. Dev Cell. 2010. PMID: 20412775 - The adventures of Sonic Hedgehog in development and repair. I. Hedgehog signaling in gastrointestinal development and disease.
Parkin CA, Ingham PW. Parkin CA, et al. Am J Physiol Gastrointest Liver Physiol. 2008 Feb;294(2):G363-7. doi: 10.1152/ajpgi.00457.2007. Epub 2007 Dec 6. Am J Physiol Gastrointest Liver Physiol. 2008. PMID: 18063705 Review. - Depletion of the colonic epithelial precursor cell compartment upon conditional activation of the hedgehog pathway.
van Dop WA, Uhmann A, Wijgerde M, Sleddens-Linkels E, Heijmans J, Offerhaus GJ, van den Bergh Weerman MA, Boeckxstaens GE, Hommes DW, Hardwick JC, Hahn H, van den Brink GR. van Dop WA, et al. Gastroenterology. 2009 Jun;136(7):2195-2203.e1-7. doi: 10.1053/j.gastro.2009.02.068. Epub 2009 Mar 6. Gastroenterology. 2009. PMID: 19272384 - The adventures of sonic hedgehog in development and repair. II. Sonic hedgehog and liver development, inflammation, and cancer.
Omenetti A, Diehl AM. Omenetti A, et al. Am J Physiol Gastrointest Liver Physiol. 2008 Mar;294(3):G595-8. doi: 10.1152/ajpgi.00543.2007. Epub 2008 Jan 24. Am J Physiol Gastrointest Liver Physiol. 2008. PMID: 18218671 Review.
Cited by
- HSulf-1 suppresses cell growth and down-regulates Hedgehog signaling in human gastric cancer cells.
Ma HY, Zhang F, Li J, Mo ML, Chen Z, Liu L, Zhou HM, Sheng Q. Ma HY, et al. Oncol Lett. 2011 Nov;2(6):1291-1295. doi: 10.3892/ol.2011.407. Epub 2011 Sep 2. Oncol Lett. 2011. PMID: 22848304 Free PMC article. - Genetic ablation of Smoothened in pancreatic fibroblasts increases acinar-ductal metaplasia.
Liu X, Pitarresi JR, Cuitiño MC, Kladney RD, Woelke SA, Sizemore GM, Nayak SG, Egriboz O, Schweickert PG, Yu L, Trela S, Schilling DJ, Halloran SK, Li M, Dutta S, Fernandez SA, Rosol TJ, Lesinski GB, Shakya R, Ludwig T, Konieczny SF, Leone G, Wu J, Ostrowski MC. Liu X, et al. Genes Dev. 2016 Sep 1;30(17):1943-55. doi: 10.1101/gad.283499.116. Epub 2016 Sep 15. Genes Dev. 2016. PMID: 27633013 Free PMC article. - The progesterone receptor regulates implantation, decidualization, and glandular development via a complex paracrine signaling network.
Wetendorf M, DeMayo FJ. Wetendorf M, et al. Mol Cell Endocrinol. 2012 Jun 24;357(1-2):108-18. doi: 10.1016/j.mce.2011.10.028. Epub 2011 Nov 17. Mol Cell Endocrinol. 2012. PMID: 22115959 Free PMC article. Review. - Subcellular distribution of patched and smoothened in the cerebellar neurons.
Petralia RS, Wang YX, Mattson MP, Yao PJ. Petralia RS, et al. Cerebellum. 2012 Dec;11(4):972-81. doi: 10.1007/s12311-012-0374-6. Cerebellum. 2012. PMID: 22477363 Free PMC article. - Novel Small Molecule Inhibitors of Cancer Stem Cell Signaling Pathways.
Abetov D, Mustapova Z, Saliev T, Bulanin D, Batyrbekov K, Gilman CP. Abetov D, et al. Stem Cell Rev Rep. 2015 Dec;11(6):909-18. doi: 10.1007/s12015-015-9612-x. Stem Cell Rev Rep. 2015. PMID: 26210995
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources