@article{6c648fe68ff6427683fd504503ac5784,
title = "BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-β-catenin signaling",
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 β-catenin. Thus, BMP signaling may control the duplication of intestinal stem cells, thereby preventing crypt fission and the subsequent increase in crypt number.",
author = "He, {Xi C.} and Jiwang Zhang and Tong, {Wei Gang} and Ossama Tawfik and Jason Ross and Scoville, {David H.} and Qiang Tian and Xin Zeng and Xi He and Wiedemann, {Leanne M.} and Yuji Mishina and Linheng Li",
note = "Funding Information: We thank P. Dijke for providing antiserum to Bmpr1a; A. McMahon, B. Hogan and C.G. Lobe for providing Nog-lacZ, BMP4-lacZ and Z/EG mice, respectively; I. Weissman and L. Alies for providing Top-d2GFP; B. Li for providing the constitutively active Akt plasmid; S. Harris for providing the constitutively activated and dominant-negative Bmpr1a cDNAs; S. Hawley and R. Krumlauf for scientific discussions; J. Haug for suggestions; J. Conaway, O. Pourqui{\'e}, S. Abmayr, P. Trainor and H. Lin for their comments regarding the manuscript; P. Trainor and A. Iulianella for assistance with the intestinal tissue culture experiments; S. Hawley, W. Cui and J. Kramer for technical advice; D. di Natale for assistance on manuscript editing; P. Kulesa and D. Stark for imaging assistance; T. Johnson and D. Grant for histological assistance; and J. William and S. Barrett for technical assistance. This work was supported by Stowers Institute for Medical Research.",
year = "2004",
month = oct,
doi = "10.1038/ng1430",
language = "English (US)",
volume = "36",
pages = "1117--1121",
journal = "Nature genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "10",
}