Hedgehog Signalling in Gut Development, Physiology and Cancer

Overview

Journal J Physiol

Specialty Physiology

Date 2011 Dec 7

PMID 22144577

Citations 39

Authors

Juanita L Merchant

Affiliations

Soon will be listed here.

Abstract

The Hedgehog pathway is one of the most common signal transduction pathways used by mammalian cells. Most studies have focused on its role during development, primarily of the nervous system, skin, bone and pancreas. Due to the activation of this pathway during proliferation and neoplastic transformation, more recent studies have examined its role in adult tissues. Significant levels of sonic hedgehog are expressed in the gastric mucosa, which has served to direct analysis of its role during organogenesis, gastric acid secretion and neoplastic transformation. Therefore the goal of this review is to apply current knowledge of this pathway to further our understanding of gastrointestinal physiology and neoplasia, using the stomach as a prototype.

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References

Goetz J, Suber L, Zeng X, Robbins D . Sonic Hedgehog as a mediator of long-range signaling. Bioessays. 2002; 24(2):157-65. DOI: 10.1002/bies.10056. View

Ivanova S, Repnik U, Bojic L, Petelin A, Turk V, Turk B . Lysosomes in apoptosis. Methods Enzymol. 2008; 442:183-99. DOI: 10.1016/S0076-6879(08)01409-2. View

Varnat F, Zacchetti G, Ruiz i Altaba A . Hedgehog pathway activity is required for the lethality and intestinal phenotypes of mice with hyperactive Wnt signaling. Mech Dev. 2009; 127(1-2):73-81. DOI: 10.1016/j.mod.2009.10.005. View

Katoh Y, Katoh M . Comparative genomics on Sonic hedgehog orthologs. Oncol Rep. 2005; 14(4):1087-90. View

Pathi S, Baker D, GARBER E, Rayhorn P, Bumcrot D, Tabin C . Comparative biological responses to human Sonic, Indian, and Desert hedgehog. Mech Dev. 2001; 106(1-2):107-17. DOI: 10.1016/s0925-4773(01)00427-0. View

Fukaya M, Isohata N, Ohta H, Aoyagi K, Ochiya T, Saeki N . Hedgehog signal activation in gastric pit cell and in diffuse-type gastric cancer. Gastroenterology. 2006; 131(1):14-29. DOI: 10.1053/j.gastro.2006.05.008. View

Adolphe C, Narang M, Ellis T, Wicking C, Kaur P, Wainwright B . An in vivo comparative study of sonic, desert and Indian hedgehog reveals that hedgehog pathway activity regulates epidermal stem cell homeostasis. Development. 2004; 131(20):5009-19. DOI: 10.1242/dev.01367. View

Dennler S, Andre J, Verrecchia F, Mauviel A . Cloning of the human GLI2 Promoter: transcriptional activation by transforming growth factor-beta via SMAD3/beta-catenin cooperation. J Biol Chem. 2009; 284(46):31523-31. PMC: 2797221. DOI: 10.1074/jbc.M109.059964. View

Reister S, Kordes C, Sawitza I, Haussinger D . The epigenetic regulation of stem cell factors in hepatic stellate cells. Stem Cells Dev. 2011; 20(10):1687-99. DOI: 10.1089/scd.2010.0418. View

10.

van Dop W, Uhmann A, Wijgerde M, Sleddens-Linkels E, Heijmans J, Offerhaus G . Depletion of the colonic epithelial precursor cell compartment upon conditional activation of the hedgehog pathway. Gastroenterology. 2009; 136(7):2195-2203.e1-7. DOI: 10.1053/j.gastro.2009.02.068. View

11.

Carpenter D, Stone D, Brush J, Ryan A, Armanini M, Frantz G . Characterization of two patched receptors for the vertebrate hedgehog protein family. Proc Natl Acad Sci U S A. 1998; 95(23):13630-4. PMC: 24870. DOI: 10.1073/pnas.95.23.13630. View

12.

Ramsey V, Doherty J, Chen C, Stappenbeck T, Konieczny S, Mills J . The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1. Development. 2006; 134(1):211-22. DOI: 10.1242/dev.02700. View

13.

Beug S, Parks R, McBride H, Wallace V . Processing-dependent trafficking of Sonic hedgehog to the regulated secretory pathway in neurons. Mol Cell Neurosci. 2010; 46(3):583-96. DOI: 10.1016/j.mcn.2010.12.009. View

14.

Ohlig S, Farshi P, Pickhinke U, Boom J, Hoing S, Jakuschev S . Sonic hedgehog shedding results in functional activation of the solubilized protein. Dev Cell. 2011; 20(6):764-74. DOI: 10.1016/j.devcel.2011.05.010. View

15.

Lee J, Ekker S, von Kessler D, Porter J, Sun B, Beachy P . Autoproteolysis in hedgehog protein biogenesis. Science. 1994; 266(5190):1528-37. DOI: 10.1126/science.7985023. View

16.

Karam S, Leblond C . Identifying and counting epithelial cell types in the "corpus" of the mouse stomach. Anat Rec. 1992; 232(2):231-46. DOI: 10.1002/ar.1092320208. View

17.

Stepan V, Ramamoorthy S, Nitsche H, Zavros Y, Merchant J, Todisco A . Regulation and function of the sonic hedgehog signal transduction pathway in isolated gastric parietal cells. J Biol Chem. 2005; 280(16):15700-8. DOI: 10.1074/jbc.M413037200. View

18.

Pazour G, Witman G . The vertebrate primary cilium is a sensory organelle. Curr Opin Cell Biol. 2003; 15(1):105-10. DOI: 10.1016/s0955-0674(02)00012-1. View

19.

Winklmayr M, Schmid C, Laner-Plamberger S, Kaser A, Aberger F, Eichberger T . Non-consensus GLI binding sites in Hedgehog target gene regulation. BMC Mol Biol. 2010; 11:2. PMC: 2830928. DOI: 10.1186/1471-2199-11-2. View

20.

Pedersen L, Veland I, Schroder J, Christensen S . Assembly of primary cilia. Dev Dyn. 2008; 237(8):1993-2006. DOI: 10.1002/dvdy.21521. View