A genetic study of the role of the Wnt/β-catenin signalling in Paneth cell differentiation

被引:94
作者
Andreu, Pauline
Peignon, Gregory
Slomianny, Christian [2 ]
Taketo, Makoto M. [3 ]
Colnot, Sabine
Robine, Sylvie [4 ]
Lamarque, Dominique [5 ]
Laurent-Puig, Pierre [6 ]
Perret, Christine
Romagnolo, Beatrice [1 ]
机构
[1] Univ Paris 05, CNRS UMR 8104, Inst Cochin, INSERM,Endocrinol Metab & Canc Dept,U567, F-75014 Paris, France
[2] INSERM, U800, Villeneuve Dascq, France
[3] Kyoto Univ, Grad Sch Med, Dept Pharmacol, Sakyo Ku, Kyoto 6068501, Japan
[4] Inst Curie, CNRS, UMR 144, F-75231 Paris, France
[5] Hop Hotel Dieu, Dept Gastroenterol, F-75181 Paris, France
[6] Univ Paris 05, Fac Med Rene Descartes, F-75014 Paris, France
关键词
beta-catenin; Intestine; Paneth cells; Differentiation;
D O I
10.1016/j.ydbio.2008.09.027
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Wnt/beta-catenin signalling plays a key role in the homeostasis of the intestinal epithelium. Whereas its role in the maintenance of the stern cell compartment has been clearly demonstrated, its role in the Paneth cell fate remains unclear We performed genetic studies to elucidate the functions of the Wnt/beta-catenin pathway in Paneth cell differentiation. We analysed mice with inducible gain-of-function mutations in the Wnt/beta-catenin pathway and mice with a hypomorphic beta-catenin allele that have not been previously described. We demonstrated that acute activation of Wnt/beta-catenin signalling induces de novo specification of Paneth cells in both the small intestine and colon and that colon cancers resulting from Apc mutations expressed many genes involved in Paneth cell differentiation. This suggests a key role for the Wnt/beta-catenin pathway in Paneth cell differentiation. We also showed that a slight decrease in beta-catenin gene dosage induced a major defect in Paneth cell differentiation, but only a modest effect on crypt morphogenesis. Overall, our findings show that a high level of beta-catenin activation is required to determine Paneth cell fate and that fine tuning of beta-catenin signalling is critical for correct Paneth cell lineage. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:288 / 296
页数:9
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