Student Theses and Dissertations

Date of Award

2010

Document Type

Thesis

RU Laboratory

Steller Laboratory

Keywords

apoptosis, neurodegeneration, programmed cell death, photoreceptors, drosophila melanogaster, ferritin

Abstract

Apoptosis, or programmed cell death, is a form of physiological cell death that is essential for normal development and homeostasis. At the end of pupal development of the Drosophila retina, cell death terminates and photoreceptor neurons complete their differentiation process. We use these terminally differentiated photoreceptor neurons as a system to study neurodegeneration. We first adapt and develop fluorescent tools for photoreceptor visualization in vivo. These tools enable a recessive genetic screen to search for genes required for the survival of differentiated photoreceptors. Many redox and mitochondrial genes were found to protect photoreceptors from late cell death. Here, we focus on the iron-storage complex, Ferritin. ferritin mutations lead to caspase activation and photoreceptor neuronal death during development and sensitize adult photoreceptor neurons to cell death stimuli. ferritin mutations provide a robust model to study the role of iron and oxidative stress in neurodegeneration. To further investigate the role of Ferritin in photoreceptor survival, we generate genetically-encoded in vivo iron and redox sensors. In summary, by developing novel tools for photoreceptor cell visualization, we explore the neuro-specific mechanisms required for lifelong photoreceptor neuron survival. We perform a photoreceptor-specific genetic screen and characterize Ferritin’s role in shielding photoreceptor cells from iron and oxidative stress-induced cell death.

Comments

A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy.

Permanent URL

http://hdl.handle.net/10209/373

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