Title

Neuronal apoptosis in adult Drosophila melanogaster

Date of Completion

January 2007

Keywords

Biology, Genetics

Degree

Ph.D.

Abstract

Abnormal regulation of neuronal apoptosis has been proposed to play a role in the pathology of several neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. The fruit fly Drosophila melanogaster, is being used as model for the study of these diseases. However, apoptosis is generally studied in the context of development of juvenile larvae. Apoptosis in fully differentiated adult neurons has not yet been well characterized. Studies have shown that apoptotic machinery has been conserved in all known metazoans. We investigated the effect of activating apoptosis in adult post-mitotic neurons by manipulating regulators of apoptosis in the adult nervous system. By using an inducible system, we are able to use a molecular genetic approach to conditionally activate apoptosis. ^ Here we present the biological consequences of over-expression of different apoptotic and anti-apoptotic genes in the nervous system of the adult fly. Expression of a dominant negative Dmp53, a drosophila homolog of p53, extended the lifespan in flies, while over-expression of other anti-apoptotic genes did not. ^ Over-expression of pro-apoptotic genes in the nervous system, led to two very distinct phenotypes. Over-expression of REAPER, led to a oviposit behavior defect, while over-expression of GRIM and DRONC led to a shortening of lifespan. However, both of these phenotypes were only seen when the fly was a young adult. When over-expression begins at a later date, there was no effect seen, suggesting that "maturation windows" that still exist in the adult fly. ^