Regulation of cell proliferation by Wnt signaling and apical-basal polarity in lung

在这项研究中，我们的目的是阐明肺分支形态发生的机制，这是由Wnt信号介导的。我们已经建立了肺上皮三维培养体系。通过使用这种方法，我们用CHIR 99021（β-连环蛋白途径的激动剂）或表达Wnt 2（β-连环蛋白依赖性途径的典型配体）的转导慢病毒处理上皮。CHIR或Wnt 2促进分枝形态建成。 β-连环蛋白途径的激活通过增强非典型PKCzeta（aPKCzeta）（顶端和基底极性的关键调节因子）对顶端膜的定位而促进顶端收缩。 此外，aPKCzeta抑制剂表现出分支形态发生和顶端收缩的缺陷。 总之，我们发现β-连环蛋白通路维持远端祖细胞，并且可证明是通过aPKCzeta的顶端靶向和顶端收缩来进行分支形态发生所需的。

In this study, we aim to elucidate the mechanism for lung branching morphogenesis which is mediated by Wnt signaling. We have already generated three dimensional culture system of lung epithelium. By using this, we treated the epithelium with CHIR99021, an agonist for beta-catenin pathway or transduced lentiviruses that express Wnt2, a typical ligand for beta-catenin dependent pathway. CHIR or Wnt2 promoted branching morphogenesis. Activation of beta-catenin pathway promoted apical constriction provably through enhanced localization of atypical PKCzeta (aPKCzeta), a critical regulator of apical and basal polarity, to apical membrane. In addition, aPKCzeta inhibitor showed the defect in branching morphogenesis and apical constriction. In conclusion, we found that beta-catenin pathway maintains distal progenitor and is required for branching morphogenesis provably through apical targeting of aPKCzeta and apical constriction.