Hippo pathway perturbation disrupts cell fate control in the Drosophila eye

Abstract

During animal development, cells acquire specialised fates in a precise spatiotemporal order, which is essential for producing tissues that function appropriately. Cell fate specification is governed by multiple signalling pathways, as well as mechanical forces, which impact cellular transcription. Two such signalling pathways are the Hippo pathway and EGFR pathway, which both control organ growth and the fate of certain cell types in multiple species. Here, we show that Hippo signalling is essential for the maintenance of the cone and primary pigment cell fates in the developing Drosophila eye. When Hippo signalling is compromised, its nuclear effectors Yorkie and Scalloped drive increased expression of the EGFR pathway transcription repressor Yan, which antagonises the cone and primary pigment cell fates. Thus, in addition to its role as a growth suppressor, Hippo signalling promotes the fate of multiple eye cells by maintaining their responsiveness to inductive cues from the EGFR pathway. AUTHOR SUMMARYAs multicellular organisms grow and develop from a zygote, individual cells become increasingly specialised. Cell fate is specified and maintained by the coordinate action of different signalling pathways, whose activity must be tightly controlled in a spatiotemporal fashion. If this fails, cell fate can be disturbed, which can cause developmental abnormalities, and diseases such as cancers. Here, we describe a new function for the Hippo signalling pathway, which was originally discovered as a regulator of Drosophila tissue growth and subsequently linked to the genesis of multiple human cancers. Hippo signalling is essential for maintaining the fate of two key cell types in the Drosophila eye, primary pigment cells and cone cells. Without Hippo signalling these cells cannot properly respond to signals from another key signalling network, the EGFR pathway. Our discoveries add to a growing literature where the Hippo growth control pathway is repurposed to control cell fate in tissues that have ceased growth.