Wnt signalling induces maturation of Paneth cells in intestinal crypts
Author: ["Johan H. van Es","Philippe Jay","Alex Gregorieff","Marielle E. van Gijn","Suzanne Jonkheer","Pantelis Hatzis","Andrea Thiele","Maaike van den Born","Harry Begthel","Thomas Brabletz","Makoto M. Taketo","Hans Clevers"]
Publication: Nature Cell Biology
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Abstract
Wnt signalling, which is transduced through β-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.
Cite this article
van Es, J., Jay, P., Gregorieff, A. et al. Wnt signalling induces maturation of Paneth cells in intestinal crypts. Nat Cell Biol 7, 381–386 (2005). https://doi.org/10.1038/ncb1240
