Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Dev Biol. 2012 Nov 15;371(2):246-55. doi: 10.1016/j.ydbio.2012.08.016. Epub 2012 Aug 30.
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.
雄激素在 UGS 内引发复杂的信号网络，触发前列腺谱系的决定和芽的形成。鉴于其在其他系统器官发生中的贡献，我们研究了经典 Wnt 信号在前列腺发育中的作用。我们开发了一种新方法，可在早期前列腺发育中实现β-连环蛋白（经典 Wnt 信号所需的转录共激活因子）的完全缺失。β-连环蛋白缺失阻断了经典 Wnt 信号，导致前列腺原基的芽生显著减少，并未能获得前列腺特性。这种对经典 Wnt 信号的需求仅限于前列腺特性鉴定的初始分子阶段的短暂关键时期。成年前列腺中β-连环蛋白的缺失对器官稳态没有显著影响。总的来说，这些数据表明β-连环蛋白和 Wnt 信号在前列腺谱系的决定和芽的生长中发挥关键作用。
