The ZO-1 protein Polychaetoid as an upstream regulator of the Hippo pathway in Drosophila.

Qingliang Sang,Baotong Xie,Hui Wu,Gang Wang,David B Morton,Claude Desplan

doi:10.1371/journal.pgen.1009894

Abstract

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.

Highlights

Generating neuronal diversity during the development of a sensory organ is a prerequisite for the organ to perceive and discriminate various external stimuli
We identified the Drosophila membrane-associated zonula occludens-1 (ZO-1) protein Pyd as an upstream regulator of the Hippo pathway to specify PR
We revealed that Pyd acts upstream of the core components and the upstream regulator Pez in the Hippo pathway, while it may function in parallel to Kib to repress Su(dx)’s activity to specify R8 subtypes

Summary

Introduction

Generating neuronal diversity during the development of a sensory organ is a prerequisite for the organ to perceive and discriminate various external stimuli. The fate of sensory neurons is progressively restricted toward terminal differentiation, generating diverse neuronal subtypes. We use the blue- and green-sensitive PR binary fate decisions in the Drosophila eye as a model to understand the role of the Hippo pathway in post-mitotic neuronal terminal differentiation. There are two main subtypes of ommatidia: pale (p) and yellow (y) ommatidia, present in the adult Drosophila eye (Fig 1B). Melt expression is activated in pR8s by the pR7-driven Activin and BMP signals and its expression leads to the transcriptional repression of wts. Wts represses melt expression in yR8s by suppressing the activity of the transcriptional coactivator Yorkie (Yki), the downstream effector of the Hippo pathway. Wts, melt and Yki form a double negative regulatory loop to ensure pR8 vs yR8 subtype fate decision (Fig 1C) [10]. Together with its DNA-binding partner Scalloped (Sd), regulates the output of the regulatory loop to promote the expression of blue-sensitive Rh5 and prevent the expression of green-sensitive Rh6 [20]

Methods

Results

Discussion

Conclusion