The Hippo pathway is an evolutionarily conserved regulator of tissue growth that integrates inputs from both polarity and actomyosin networks. An upstream activator of the Hippo pathway, Kibra, localizes at the junctional and medial regions of the apical cortex in epithelial cells, and medial accumulation promotes Kibra activity. Here, we demonstrate that cortical Kibra distribution is controlled by a tug-of-war between apical polarity and actomyosin dynamics. We show that while the apical polarity network, in part via atypical protein kinase C (aPKC), tethers Kibra at the junctional cortex to silence its activity, medial actomyosin flows promote Kibra-mediated Hippo complex formation at the medial cortex, thereby activating the Hippo pathway. This study provides a mechanistic understanding of the relationship between the Hippo pathway, polarity, and actomyosin cytoskeleton, and it offers novel insights into how fundamental features of epithelial tissue architecture can serve as inputs into signaling cascades that control tissue growth, patterning, and morphogenesis.

Hippo 通路是一种进化上保守的组织生长调节因子，它整合了来自极性和肌动球蛋白网络的输入。Hippo 通路的上游激活剂 Kibra 位于上皮细胞顶端皮层的交界区和内侧区域，内侧积累促进 Kibra 活性。在这里，我们证明了皮质 Kibra 分布受顶端极性和肌动球蛋白动力学之间的拉锯战控制。我们表明，虽然顶端极性网络部分通过非典型蛋白激酶 C （aPKC） 将 Kibra 拴在交界皮层以使其活动沉默，但内侧肌动球蛋白流促进 Kibra 介导的 Hippo 复合物在内侧皮层形成，从而激活 Hippo 通路。这项研究提供了对 Hippo 通路、极性和肌动球蛋白细胞骨架之间关系的机制理解，并为上皮组织结构的基本特征如何作为控制组织生长、模式化和形态发生的信号级联的输入提供了新的见解。