Letter abstract
Nature Cell Biology 7, 381 - 386 (2005)
Published online: 20 March 2005 | doi:10.1038/ncb1240
Wnt signalling induces maturation of Paneth cells in intestinal crypts
Johan H. van Es1,5, Philippe Jay2,5, Alex Gregorieff1,5, Marielle E. van Gijn1, Suzanne Jonkheer1, Pantelis Hatzis1, Andrea Thiele1, Maaike van den Born1, Harry Begthel1, Thomas Brabletz3, Makoto M. Taketo4 & Hans Clevers1
Wnt signalling, which is transduced through 
-catenin/TCF4, maintains the undifferentiated state of intestinal crypt progenitor cells1, 2. Mutational activation of the pathway initiates the adenomacarcinoma sequence3, 4. Whereas all other differentiated epithelial cells migrate from the crypt onto the villus, Paneth cells home towards the source of Wnt signals — that is, the crypt bottom. Here, we show that expression of a Paneth gene programme is critically dependent on TCF4 in embryonic intestine. Moreover, conditional deletion of the Wnt receptor Frizzled-5 abrogates expression of these genes in Paneth cells in the adult intestine. Conversely, adenomas in Apc-mutant mice and colorectal cancers in humans inappropriately express these Paneth-cell genes. These observations imply that Wnt signals in the crypt can separately drive a stem-cell/progenitor gene programme and a Paneth-cell maturation programme. In intestinal cancer, both gene programmes are activated simultaneously.
- Hubrecht Institute, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584CT Utrecht, The Netherlands.
- Institut de Génétique Humaine (IGH), CNRS UPR 1142, 141 rue de la Cardonille, 34396 Montpellier cedex 5, France.
- University of Erlangen, Department of Pathology, Krankenhaustr. 8-10, 91054 Erlangen, Germany.
- Department of Pharmacology, Kyoto University Graduate School of Medicine, Yoshida-Konoé-cho, Sakyo-ku, Kyoto 606-8501, Japan.
- These authors contributed equally to this work.
Correspondence to: Hans Clevers1 e-mail: clevers@niob.knaw.nl
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