Wang Xianping, Liang Hui, Xu Wenyan, Ma Xianjue
Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.
Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
Front Cell Dev Biol. 2021 Apr 16;9:658288. doi: 10.3389/fcell.2021.658288. eCollection 2021.
Both Hippo signaling pathways and cell polarity regulation are critical for cell proliferation and the maintenance of tissue homeostasis, despite the well-established connections between cell polarity disruption and Hippo inactivation, the molecular mechanism by which aberrant cell polarity induces Hippo-mediated overgrowth remains underexplored. Here we use wing discs as a model and identify the Wnd-Nmo axis as an important molecular link that bridges loss-of-cell polarity-triggered Hippo inactivation and overgrowth. We show that Wallenda (Wnd), a MAPKKK (mitogen-activated protein kinase kinase kinase) family member, is a novel regulator of Hippo pathways in and that overexpression of Wnd promotes growth via Nemo (Nmo)- mediated Hippo pathway inactivation. We further demonstrate that both Wnd and Nmo are required for loss-of-cell polarity-induced overgrowth and Hippo inactivation. In summary, our findings provide a novel insight on how cell polarity loss contributes to overgrowth and uncover the Wnd-Nmo axis as an essential additional branch that regulates Hippo pathways in .
尽管细胞极性破坏与Hippo信号通路失活之间的联系已得到充分证实，但Hippo信号通路和细胞极性调节对于细胞增殖和组织稳态的维持都至关重要，异常细胞极性诱导Hippo介导的过度生长的分子机制仍未得到充分探索。在这里，我们以翅芽为模型，鉴定出Wnd-Nmo轴是连接细胞极性丧失引发的Hippo信号通路失活和过度生长的重要分子纽带。我们发现，丝裂原活化蛋白激酶激酶激酶（MAPKKK）家族成员Wallenda（Wnd）是Hippo信号通路在[具体生物或组织]中的一种新型调节因子，并且Wnd的过表达通过Nemo（Nmo）介导的Hippo信号通路失活促进生长。我们进一步证明，Wnd和Nmo都是细胞极性丧失诱导的过度生长和Hippo信号通路失活所必需的。总之，我们的研究结果为细胞极性丧失如何导致过度生长提供了新的见解，并揭示了Wnd-Nmo轴是[具体生物或组织]中调节Hippo信号通路的一个重要额外分支。
