BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling

Nature Genetics
Xi C HeLinheng Li

Abstract

In humans, mutations in BMPR1A, SMAD4 and PTEN are responsible for juvenile polyposis syndrome, juvenile intestinal polyposis and Cowden disease, respectively. The development of polyposis is a common feature of these diseases, suggesting that there is an association between BMP and PTEN pathways. The mechanistic link between BMP and PTEN pathways and the related etiology of juvenile polyposis is unresolved. Here we show that conditional inactivation of Bmpr1a in mice disturbs homeostasis of intestinal epithelial regeneration with an expansion of the stem and progenitor cell populations, eventually leading to intestinal polyposis resembling human juvenile polyposis syndrome. We show that BMP signaling suppresses Wnt signaling to ensure a balanced control of stem cell self-renewal. Mechanistically, PTEN, through phosphatidylinosital-3 kinase-Akt, mediates the convergence of the BMP and Wnt pathways on control of beta-catenin. Thus, BMP signaling may control the duplication of intestinal stem cells, thereby preventing crypt fission and the subsequent increase in crypt number.

References

May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·Y MiyoshiG Petersen
Nov 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·K A RothJ I Gordon
Jun 6, 1998·Science·J R HoweL A Aaltonen
Sep 1, 1999·European Journal of Biochemistry·A BessonV W Yong
Jun 24, 2000·Molecular and Cellular Biology·F VazquezW R Sellers
Sep 26, 2000·Developmental Dynamics : an Official Publication of the American Association of Anatomists·D J Roberts
Dec 6, 2000·Genesis : the Journal of Genetics and Development·A NovakC G Lobe
Dec 6, 2000·European Journal of Biochemistry·S ItohP Ten Dijke
Jun 8, 2001·The American Journal of Pathology·G L Mutter
Jul 13, 2002·The Journal of Pathology·Mairi Brittan, Nicholas A Wright
Mar 7, 2003·Human Molecular Genetics·Kristin A Waite, Charis Eng
Apr 30, 2003·Nature·Tannishtha ReyaIrving L Weissman
Oct 4, 2003·Nature Reviews. Genetics·Kristin A Waite, Charis Eng
Dec 4, 2003·Current Opinion in Cell Biology·Elena SanchoHans Clevers
Mar 16, 2004·Science·Anna-Pavlina G HaramisHans Clevers

❮ Previous
Next ❯

Citations

Jan 11, 2005·The Journal of Pathology·Mohammad Ilyas
Apr 22, 2009·International Journal of Colorectal Disease·Hui-Min Chen, Jing-Yuan Fang
Mar 3, 2010·International Journal of Colorectal Disease·Xiang-Shan FanQin Huang
Sep 11, 2007·Cell and Tissue Research·Theologos M Michaelidis, D Chichung Lie
Oct 17, 2007·Cell and Tissue Research·Malcolm R AlisonSimon Leedham
Dec 27, 2008·Bulletin of Experimental Biology and Medicine·L A VedinaV A Kozlov
Apr 15, 2006·Digestive Diseases and Sciences·Adrian G CumminsFiona M Thompson
Apr 7, 2007·Digestive Diseases and Sciences·Barbara A E de KoningAlexandra W C Einerhand
Mar 16, 2007·Digestive Diseases and Sciences·Kimberley S CamacAdrian G Cummins
Oct 10, 2006·Reviews in Endocrine & Metabolic Disorders·Elisabetta Gazzerro, Ernesto Canalis
Apr 7, 2009·In Vitro Cellular & Developmental Biology. Animal·Emily HaysNalini Chandar
Jan 30, 2013·Chinese Journal of Cancer Research = Chung-kuo Yen Cheng Yen Chiu·Fen-Xia LiMing Li
Aug 5, 2010·Current Gastroenterology Reports·Shahid Umar
Jul 13, 2007·Stem Cell Reviews·Tzung-Hai Yen, Nicholas A Wright
Dec 14, 2011·Journal of Physiology and Biochemistry·P García-MirandaA A Ilundáin
May 6, 2005·Cytokine & Growth Factor Reviews·Satoshi Kishigami, Yuji Mishina
Jun 9, 2005·Progress in Retinal and Eye Research·Ani V DasIqbal Ahmad
Nov 10, 2012·Chemical Research in Toxicology·Erik J TokarMichael P Waalkes
Nov 13, 2008·Cell Research·Xing Guo, Xiao-Fan Wang
Dec 31, 2008·Cell Research·Tetsuro Watabe, Kohei Miyazono
Nov 23, 2011·Cell Research·Catherine Legraverend, Philippe Jay
Apr 15, 2005·Nature·Tannishtha Reya, Hans Clevers
Mar 1, 2013·Nature·Simon J A BuczackiDouglas J Winton
Nov 29, 2011·Nature Cell Biology·Shalev ItzkovitzAlexander van Oudenaarden
Mar 31, 2011·Nature Communications·Marion EscobarCatherine Legraverend
Sep 30, 2004·Nature Genetics·Gijs R van den Brink
Oct 1, 2005·Nature Genetics·Matthew Bjerknes, Hazel Cheng
Dec 30, 2004·Nature Genetics·Ken InokiKun-Liang Guan
Sep 9, 2005·Nature Reviews. Cancer·Thomas BrabletzThomas Kirchner
May 25, 2007·Nature Reviews. Cancer·John D Potter
Apr 25, 2008·Nature Reviews. Cancer·Alexandra Klaus, Walter Birchmeier
Aug 30, 2008·Nature Reviews. Cancer·James C HardwickGijs R van den Brink
Sep 12, 2008·Nature Reviews. Cancer·Jane E Visvader, Geoffrey J Lindeman
Nov 4, 2009·Nature Reviews. Gastroenterology & Hepatology·Michael Quante, Timothy C Wang
Feb 5, 2011·Nature Reviews. Gastroenterology & Hepatology·Sebastian S ZekiNicholas A Wright
Jan 24, 2012·Nature Reviews. Molecular Cell Biology·Ya-Chieh Hsu, Elaine Fuchs
Dec 12, 2013·Nature Reviews. Molecular Cell Biology·Nick Barker
Dec 21, 2006·Cell Research·Feng LiYibin Kang
Jan 3, 2007·Cell Research·Dániel Kirilly, Ting Xie
Dec 5, 2006·Oncogene·A R Clarke

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adenomatous Polyposis Coli

Adenomatous polyposis coli is a protein encoded by the APC gene and acts as a tumor suppressor. Discover the latest research on adenomatous polyposis coli here.

Related Papers

Developmental Dynamics : an Official Publication of the American Association of Anatomists
Lorene E BattsHolger Kulessa
Differentiation; Research in Biological Diversity
Christopher S PottenHideyuki Okano
Nature Genetics
Eugenio Sangiorgi, Mario R Capecchi
© 2021 Meta ULC. All rights reserved