Date of Award

8-2016

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Biochemistry and Cellular and Molecular Biology

Major Professor

Jae H. Park

Committee Members

Bruce McKee, Rebecca Prosser, Ranjan Ganguly, Juan Luis Jurat-Fuentes

Abstract

Almost all living organisms have circadian clocks coordinating physiology and behavior, and an innate molecular clock drives rhythmic changes by integrating environmental and metabolic stimuli to generate 24 hour timing. Drosophila melanogaster has proved to be an excellent model organism with a well-characterized circadian clock and the neural circuits underlying clock have been intensely investigated. The neuropeptide pigment-dispersing factor (PDF) plays an essential role in maintaining circadian rhythmicity and synchronizes circadian clock neurons. However, the regulation of Pdf has been a black box with no known protein identified that directly regulates it, and its role in metabolism hasn’t been looked into. In addition, the role of different signaling pathways that work in the PDF expressing neurons to integrate circadian period also needs to be explored. The collection of work presented here addresses some of these concerns. Chapter II outlines the role of a transcription factor in spatially restricting Pdf expression to the ventral lateral neurons that express this neuropeptide. We have identified a cis-regulatory element in the promoter of Pdf that is sufficient for its expression in the ventral lateral neurons. In addition, we have identified a novel homeodomain transcription factor scarecrow (scro) that directly binds and negatively regulates Pdf. Chapter III aims to characterize the function of scro in tissue identity and specification during Drosophila development. Here, we have outlined the possible mechanism by which scro plays a role in proper development of tissues. Chapter IV addresses the role of transforming growth factor – beta (TGF-β) in PDF neurons. Furthermore, we have identified a Type I receptor in this signaling pathway that downregulates Pdf and is key to maintaining circadian rhythmicity. Finally, Chapter V addresses the role of PDF signaling pathway in caffeine metabolism, thus linking central clock to metabolism. We hypothesize the importance of PDF in regulating cytochrome genes induced in response to caffeine. Taken collectively, this body of work enhances our present understanding of Pdf regulation in addition to identifying the role of TGF-β signaling in the PDF expressing neurons. This study also identifies novel role of scro during Drosophila development.

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