Yorkie facilitates cell survival during larval eye development in Drosophila melanogaster

We are using the Drosophila eye as a model system because it is a well characterized developmental model that grows from a single layer of epithelial tissue. YAP1, the human homolog of Yki, is a transcription factor that has been found to be highly expressed and localized in the nucleus of several human cancers, suggesting that having a better understanding of the time and spatial role of Yki in eye development may help to better understand the molecular consequences of YAP1 up-regulation in human cancer. During Drosophila development, the eye utilizes the morphogenetic furrow to facilitate a progressive pattern of differentiation. To understand how key signaling pathways result in not only furrow progression but also cell survival we are primarily focusing on the time dependent knockdown of the transcription regulatory protein Yorkie (Yki) by utilizing both RNAi and the Flp/FRT systems to disrupt Yorkie expression. Previous studies have shown Yki to be involved with cell survival, cell growth and cell proliferation, though many of those studies have been in genetic systems in which Yki is over active. Here we show that Yki is essential for survival and a knockdown of Yki results in increased cell death in larval discs, disrupted ommatidia in pupal discs, and drastically smaller adult eye phenotypes. This increase in cell apoptosis coincides with a decrease in DIAP1 (a known Yki transcriptional target). To investigate additional potential roles of Yki in eye development we used the FLP/FRT system to create mosaic eye discs where clones have both a loss of Yki expression and a block in the canonical apoptotic pathway. Cell death was inhibited through a loss of function Ark allele. With the addition of the Ark allele, the Yki/ark mosaic eyes show a rescue of clone size in both larval and adult eyes. Contrary to the understood role of Yki involved with cell growth and cell cycle regulation we see no disruption in patterns of mitosis, differentiation, or other developmental signaling pathways. Our studies suggest that while Yorkie may facilitate overgrowth and over-proliferation in certain mutant genetic contexts, that its role in early eye development is primarily cell survival.