Wnt signaling though beta-catenin is required for prostate lineage specification

被引:40
|
作者
Simons, Brian W. [1 ,2 ]
Hurley, Paula J. [3 ]
Huang, Zhenhua [3 ]
Ross, Ashley E. [2 ,3 ,4 ]
Miller, Rebecca [3 ]
Marchionni, Luigi [4 ]
Berman, David M. [2 ,3 ,4 ]
Schaeffer, Edward M. [3 ,4 ]
机构
[1] Johns Hopkins Univ, Dept Mol & Comparat Pathobiol, Sch Med, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Dept Pathol, Sch Med, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Dept Urol, Sch Med, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Dept Oncol, Sch Med, Baltimore, MD 21205 USA
关键词
Wnt signaling; Prostate development; Urogenital sinus; Mouse; MOUSE PROSTATE; BRANCHING MORPHOGENESIS; ORGAN-CULTURE; EXPRESSION; GROWTH; GENE; PATHWAY; CANCER; NKX3.1; AXIN2;
D O I
10.1016/j.ydbio.2012.08.016
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Androgens initiate a complex network of signals within the UGS that trigger prostate lineage commitment and bud formation. Given its contributions to organogenesis in other systems, we investigated a role for canonical Wnt signaling in prostate development. We developed a new method to achieve complete deletion of beta-catenin, the transcriptional coactivator required for canonical Wnt signaling, in early prostate development. Beta-catenin deletion abrogated canonical Wnt signaling and yielded prostate rudiments that exhibited dramatically decreased budding and failed to adopt prostatic identity. This requirement for canonical Wnt signaling was limited to a brief critical period during the initial molecular phase of prostate identity specification. Deletion of beta-catenin in the adult prostate did not significantly affect organ homeostasis. Collectively, these data establish that beta-catenin and Wnt signaling play key roles in prostate lineage specification and bud outgrowth. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:246 / 255
页数:10
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