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

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ID: 270918
2004
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Abstract
In humans, mutations in BMPR1A, SMAD4 and PTEN are responsible for juvenile polyposis syndrome1, juvenile intestinal polyposis2 and Cowden disease3, respectively. The development of polyposis is a common feature of these diseases, suggesting that there is an association between BMP and PTEN pathways4,5. 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.
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Authors He, Xi C;Zhang, Jiwang;Tong, Wei-Gang;Tawfik, Ossama;Ross, Jason;Scoville, David H;Tian, Qiang;Zeng, Xin;He, Xi;Wiedemann, Leanne M;Mishina, Yuji;Li, Linheng;He, Xi C;Zhang, Jiwang;Tong, Wei-Gang;Tawfik, Ossama;Ross, Jason;Scoville, David H;Tian, Qiang;Zeng, Xin;He, Xi;Wiedemann, Leanne M;Mishina, Yuji;Li, Linheng;
Journal nature genetics
Year 2004
DOI
doi:10.1038/ng1430
URL
http://dx.doi.org/10.1038/ng1430
Keywords
agriculture biomedicine cancer research general animal genetics and genomics human genetics gene function

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