Integrative Biomedical and Diagnostic Sciences Department, School of Dentistry, Oregon Health and Science University, Portland, Oregon, United States of America.
PLoS Genet. 2021 Nov 8;17(11):e1009894. doi: 10.1371/journal.pgen.1009894. eCollection 2021 Nov.
The generation of a diversity of photoreceptor (PR) subtypes with different spectral sensitivities is essential for color vision in animals. In the Drosophila eye, the Hippo pathway has been implicated in blue- and green-sensitive PR subtype fate specification. Specifically, Hippo pathway activation promotes green-sensitive PR fate at the expense of blue-sensitive PRs. Here, using a sensitized triple heterozygote-based genetic screening approach, we report the identification of the single Drosophila zonula occludens-1 (ZO-1) protein Polychaetoid (Pyd) as a new regulator of the Hippo pathway during the blue- and green-sensitive PR subtype binary fate choice. We demonstrate that Pyd acts upstream of the core components and the upstream regulator Pez in the Hippo pathway. Furthermore, We found that Pyd represses the activity of Su(dx), a E3 ligase that negatively regulates Pez and can physically interact with Pyd, during PR subtype fate specification. Together, our results identify a new mechanism underlying the Hippo signaling pathway in post-mitotic neuronal fate specification.
产生具有不同光谱敏感性的多种光感受器（PR）亚型对于动物的色觉至关重要。在果蝇眼中，Hippo 途径已被牵涉到蓝敏和绿敏 PR 亚型命运特化。具体来说，Hippo 途径的激活促进了绿敏 PR 命运的产生，而牺牲了蓝敏 PR。在这里，我们使用一种敏化的三重杂合子遗传筛选方法，报告了鉴定出果蝇单一的紧密连接蛋白-1（ZO-1）Polychaetoid（Pyd）作为 Hippo 途径在蓝敏和绿敏 PR 亚型二元命运选择过程中的新调节因子。我们证明了 Pyd 在 Hippo 途径的核心成分和上游调节剂 Pez 的上游起作用。此外，我们发现 Pyd 在 PR 亚型命运特化过程中抑制了 E3 连接酶 Su(dx)的活性，Su(dx)负调控 Pez，并且可以与 Pyd 物理相互作用。总之，我们的结果确定了 Hippo 信号通路在有丝后神经元命运特化中的一个新机制。
