Expanded roles of IAP inhibitors and the caspase pathway in damaged and regenerating imaginal wing disc tissue

D'Ancona, Cristina, Biology - Graduate School of Arts and Sciences, University of Virginia
Halme, Adrian, MD-CELL Cell Biology, University of Virginia
Keller, Raymond, AS-Biology, University of Virginia
Hirsh, Jay, AS-Biology, University of Virginia
Siegrist, Sarah, AS-Biology, University of Virginia
Bland, Michelle, MD-PHAR Pharmacology, University of Virginia
Bergland, Alan, AS-Biology, University of Virginia

Caspase-mediated cell death is critical for development and stress responses1 but my data indicates caspase-mediated cell death—referred to from here out as apoptosis—may also have other roles. During regeneration after damage, apoptosis is necessary to clear injured tissues and make way for new growth2. My thesis research explores the role of apoptosis and pro-apoptotic proteins Reaper, Grim, and Hid (RGH) during damage and regeneration. RGH proteins bind Inhibitors of Apoptosis Proteins (IAPs) and induce IAP auto-ubiquitination/degradation to promote programmed cell death3,4. Chapter 2 describes experiments demonstrating that apoptosis is necessary to prevent overgrowth and tumorigenesis in regenerating tissues. Chapter 3 describes experiments showing that IAP inhibitor expression in the wing imaginal disc produces non-autonomous larval growth inhibition. Thus, the experiments in this thesis describe two new roles for apoptosis and IAP-inhibitor proteins following damage and during regeneration beyond the clearance of injured cells: limiting regeneration and causing non-autonomous larval and pupal growth inhibition.

PHD (Doctor of Philosophy)
cell death, regeneration, growth inhibition, neoplasia
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