TY - JOUR
T1 - Wnt signalling induces maturation of Paneth cells in intestinal crypts
AU - van Es, Johan H.
AU - Jay, Philippe
AU - Gregorieff, Alex
AU - van Gijn, Marielle E.
AU - Jonkheer, Suzanne
AU - Hatzis, Pantelis
AU - Thiele, Andrea
AU - van den Born, Maaike
AU - Begthel, Harry
AU - Brabletz, Thomas
AU - Taketo, Makoto M.
AU - Clevers, Hans
PY - 2005/4/1
Y1 - 2005/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=20244364236&partnerID=8YFLogxK
U2 - 10.1038/ncb1240
DO - 10.1038/ncb1240
M3 - Article
C2 - 15778706
AN - SCOPUS:20244364236
SN - 1465-7392
VL - 7
SP - 381
EP - 386
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 4
ER -