Date of Award

12-2019

Document Type

Campus Access Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Jens Rister

Second Advisor

Michael Shiaris

Third Advisor

Alexey Veraksa

Abstract

The highly conserved Hippo tumor suppressor pathway controls the growth of tissues and organs by regulating cell proliferation and apoptosis. The Hippo pathway also plays an important role in patterning the color-sensing photoreceptors in the Drosophila retina. In this context, the Hippo pathway acts as a bistable switch, whereby the pathway is either “on” giving rise to green-sensitive (Rh6-expressing) photoreceptors, or “off” giving rise to blue-sensitive (Rh5-expressing) photoreceptors. Here, we study a mutation in an unknown gene we have termed “daltonien” that causes a dramatic loss of blue-sensitive photoreceptors and gain of green-sensitive photoreceptors. As a consequence, the mutant is impaired in discriminating blue and green colors. However, it is currently unknown how daltonien regulates the Hippo Pathway. We show that daltonien is required to repress the Hippo Pathway and green/Rh6 fate in order to specify blue/Rh5 fate. Our epistasis experiments revealed that daltonien acts downstream of the Babo type I receptor for activin-like ligands that receives the blue/Rh5-inducing signal. daltonien also acts upstream of the PH domain containing protein Melted, as well as the Warts kinase, which is the nexus of the Hippo pathway. daltonien promotes the transcription of melted and inhibits the transcription of warts. Lastly, using deletions, duplications, and qPCR, we have narrowed down a 56kb region on the X chromosome and several candidate genes for daltonien. Taken together, daltonien is required for the proper ratio of color-sensing photoreceptors as well as color vision. Given that color blindness in humans is also caused by mutations, it is crucial to determine if there is a human orthologue of daltonien that also plays a role in color vision or the regulation of the Hippo pathway.

Comments

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