Hippo pathway and Bonus control developmental cell fate decisions in the Drosophila eye

The canonical function of the Hippo signaling pathway is the regulation of organ growth. How this pathway controls cell fate determination is less well understood. Here, we identify a function of the Hippo pathway in cell fate decisions in the developing Drosophila eye, exerted through the interaction of Yorkie (Yki) with the transcriptional regulator Bonus (Bon), an ortholog of mammalian Transcriptional Intermediary Factor 1/tripartite motif (TIF1/TRIM) family proteins. Instead of controlling tissue growth, Yki and Bon promote epidermal and antennal fates at the expense of the eye fate. Proteomic, transcriptomic, and genetic analyses reveal that Yki and Bon control these cell fate decisions by recruiting transcriptional and post-transcriptional co-regulators, and by repressing Notch target genes and activating epidermal differentiation genes. Our work expands the range of functions and regulatory mechanisms under Hippo pathway control. To identify the transcriptional output of Yki and Bon in the eye vs. epidermis cell fate determination, we performed RNA sequencing to examine the transcriptome of pupal eyes at 40-41 hrs after puparium formation (APF), when the ectopic epidermal trichomes in the eye initiate, upon Bon overexpression, with or without simultaneous knockdown of Yki using RNAi, under the eye-specific driver GMR-GAL4. Three biological replicates were analyzed for each condition: mCherry (WT control), Bon-mCherry, and Bon-mCherry + yki-RNAi.