Wnt signalling induces maturation of Paneth cells in intestinal crypts

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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

532 Citaten (Scopus)

Samenvatting

Wnt signalling, which is transduced through β-catenin/TCF4, maintains the undifferentiated state of intestinal crypt progenitor cell. Mutational activation of the pathway initiates the adenomacarcinoma sequence. 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.

Originele taal-2Engels
Pagina's (van-tot)381-386
Aantal pagina's6
TijdschriftNature Cell Biology
Volume7
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - apr. 2005
Extern gepubliceerdJa

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