Wnt/β-catenin signaling in the dental mesenchyme regulates incisor development by regulating Bmp4

被引:93
作者
Fujimori, Sayumi [1 ]
Novak, Hermann [1 ]
Weissenboeck, Martina [1 ]
Jussila, Maria [2 ]
Goncalves, Alexandre [3 ]
Zeller, Rolf [3 ]
Galloway, Jenna [4 ]
Thesleff, Irma [2 ]
Hartmann, Christine [1 ]
机构
[1] Res Inst Mol Pathol, A-1030 Vienna, Austria
[2] Univ Helsinki, Vikki Bioctr, Inst Biotechnol, Dev Biol Program, FIN-00014 Helsinki, Finland
[3] Univ Basel, Dept Biomed, CH-4058 Basel, Switzerland
[4] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA
基金
奥地利科学基金会; 瑞士国家科学基金会;
关键词
Canonical Wnt-signaling; Tooth development; Mesenchyme; BMP; Msx1; Shh; Incisor; Supernumerary; HAIR FOLLICLE DEVELOPMENT; TOOTH ENAMEL KNOT; BETA-CATENIN; CRE RECOMBINASE; MULTIPLE ROLES; MOUSE; WNT; MORPHOGENESIS; EXPRESSION; MICE;
D O I
10.1016/j.ydbio.2010.09.009
中图分类号
Q [生物科学];
学科分类号
090105 [作物生产系统与生态工程];
摘要
Loss- and gain-of function approaches modulating canonical Wnt/beta-catenin activity have established a role for the Wnt/beta-catenin pathway during tooth development. Here we show that Wnt/beta-catenin signaling is required in the dental mesenchyme for normal incisor development, as locally restricted genetic inactivation of beta-catenin results in a splitting of the incisor placode, giving rise to two incisors. Molecularly this is first associated with down-regulation of Bmp4 and subsequent splitting of the Shh domain at a subsequent stage. The latter phenotype can be mimicked by ectopic application of the BMP antagonist Noggin. Conditional genetic inactivation of Bmp4 in the mesenchyme reveals that mesenchymal BMP4 activity is required for maintenance of Shh expression in the dental ectoderm. Taken together our results indicate that beta-catenin together with Left and Tcf1 are required to activate Bmp4 expression in order to maintain Shh expression in the dental ectoderm. This provides a mechanism whereby the number of incisors arising from one placode can be varied through local alterations of a mesenchymal signaling circuit involving beta-catenin, Lef1, Tcf1 and Bmp4. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:97 / 106
页数:10
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