Genetic and environmental regulation of stem cells and their progeny in the Drosophila melanogaster testis

Abstract

Stem cells are required in adult animals to replenish certain tissues throughout the life of an individual. Exploring the fundamental principles that regulate stem cell behavior in animals is crucial to both realizing their therapeutic potential and understanding the pathological roles they may play in cancer etiology. The work reported in this thesis has employed the population of germline stem cells (GSCs) residing in the testis of the genetically tractable Drosophila melanogaster as a model to gain general insights into how stem cells function to create tissue homeostasis, how stem cells interact with their cellular microenvironment, and how the differentiation of their daughters is regulated. In Chapter 2, we report that the mitotic activity of GSCs is increased in males upon exposure to females, uncovering a pathway linking the demand for sperm to the frequency of GSC divisions. We show that while the GSC response to females requires physical contact, it appears to be regulated independently of pathways previously reported to affect the frequency of stem cell divisions. In Chapter 3, we report that communication between GSCs and the surrounding soma via the Epidermal Growth Factor (EGF) signaling pathway is required to repress the frequency of GSC divisions. This role for EGF signaling in repressing the frequency of GSC divisions was both genetically and developmentally distinct from the previously reported role of EGF in promoting germ cell differentiation. Thus, these findings represent a novel role for the stem cell microenvironment in repressing stem cell divisions. In Chapter 4, studies on a mutation in a conserved nucleoporin locus reveal a role for nucleoporins in the transit amplification divisions of stem cell daughters. The findings reported in this thesis contribute to our understanding of the fundamental principles that govern stem cell biology.