Date of Award


Document Type

Campus Access Thesis

Degree Name

Master of Science (MS)



First Advisor

Jens Rister

Second Advisor

Alexey Veraksa

Third Advisor

Kellee Siegfried-Harris


The conserved Hippo tumor suppressor pathway balances cell proliferation and apoptosis. In Drosophila melanogaster, the Hippo pathway also plays a non-canonical role to post-mitotically regulate the specification of color-sensing photoreceptors. Green-sensitive (Rh6) or blue-sensitive (Rh5) pigments are expressed when the Hippo pathway is ON or OFF, respectively. I used the Drosophila eye as a model to identify novel regulators of the Hippo pathway. First, I investigated “daltonien”, a mutation that causes a dramatic loss of Rh5 photoreceptors and gain of Rh6 photoreceptors, and narrowed down a potentially affected gene. Moreover, I performed two high throughput screens to identify novel regulators of the pathway in vivo. First, I pursued an RNAi-based water immersion approach with a post-mitotic photoreceptor-specific driver (lGMR-Gal4) and a Rh5>GFP reporter as a readout for Rh5 (Hippo OFF) photoreceptors. We performed a differential gene expression analysis on transcriptomes of Rh6 (Hippo ON) and Rh5 (Hippo OFF) photoreceptors and screened for genes whose knockdown caused a deviation from the wildtype 35:65 Rh5:Rh6 photoreceptors ratio. I identified 17 genes as potential regulators of the pathway. Next, I pursued a CRISPR/Cas9-based approach to identify G-protein coupled receptors (GPCRs) that regulate the pathway in early or late eye development. I used gRNA lines for all known Drosophila GPCRs (from Dr. Schlichting, Brandeis) in combination with the eye-specific driver GMR-GAL4 to screen for GPCRs whose knockout caused adult eye defects. I also used the binary readout of Rh5 vs. Rh6 fate to identify GPCRs that regulate the Hippo pathway in terminal fate decisions. I identified 11 GPCRs required for eye development and one regulator of the Hippo pathway in the post-mitotic context. Taken together, I identified novel regulators of the Hippo pathway in eye growth and post-mitotic photoreceptor fate decisions. These findings could inspire the development of novel drugs and cancer therapies.


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