Wnt signalling induces maturation of Paneth cells in intestinal crypts.

TY - JOUR

T1 - Wnt signalling induces maturation of Paneth cells in intestinal crypts.

AU - Es, J.H. van

AU - Jay, P.

AU - Gregorieff, A.

AU - Gijn, M.E. van

AU - Jonkheer, S.

AU - Hatzis, P.

AU - Thiele, A.

AU - Born, M. van den

AU - Gegthel, H.

AU - Brabletz, T.

AU - Taketo, M.M.

AU - Clevers, J.C.

N1 - doi: 10.1038/ncb1240

PY - 2005

Y1 - 2005

N2 - Wnt signalling, which is transduced through beta-catenin/TCF4, maintains the undifferentiated state of intestinal crypt progenitor cells. 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 beta-catenin/TCF4, maintains the undifferentiated state of intestinal crypt progenitor cells. 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.

M3 - Article

SN - 1465-7392

VL - 7

SP - 381

EP - 386

JO - Nature Cell Biology

JF - Nature Cell Biology

ER -