Wallenda-Nmo Axis Regulates Growth via Hippo Signaling

• Main Authors: Xianping Wang, Hui Liang, Wenyan Xu, Xianjue Ma
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-04-01
• Series: Frontiers in Cell and Developmental Biology
• Subjects: Wnd; Hippo signaling; Nmo; growth; Drosophila
• Online Access: https://www.frontiersin.org/articles/10.3389/fcell.2021.658288/full

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 Drosophila 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 Drosophila 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 Drosophila.