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

Xi C. He, Jiwang Zhang, Wei Gang Tong, Ossama Tawfik, Jason Ross, David H. Scoville, Qiang Tian, Xin Zeng, Xi He, Leanne M. Wiedemann, Yuji Mishina, Linheng Li

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1117-1121
Number of pages5
JournalNature genetics
Volume36
Issue number10
DOIs
StatePublished - Oct 2004
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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