THE ROLE OF HNRNPS ON THE ESTABLISHMENT AND MAINTENANCE OF GERMLINE STEM CELLS IN DROSOPHILA MELANOGASTER

Abstract

An organism’s ability to grow and regulate tissue repair relies on the stimulation of stem cells in response to changes in physiological state, such as cell damage, sexual maturation and growth. Tissue-resident stem cells are capable of long-term self-renewal to maintain a steady stem cell population and produce daughter cells that can differentiate into specialized cells. Stem cell self-renewal is influenced by local signals and long-range hormonal signals, but the signaling pathway undergoes complex regulation that requires further elucidation. Individual members of a family of RNA binding proteins called heterogeneous nuclear ribonucleoproteins have been implicated in the regulation of stem cells. Drosophila melanogaster is a well-characterized ovarian system with easily-accessible germline stem cells (GSCs), making it an excellent system for the study of which hnRNPs regulate stem cell function. Using a transgenic resource of endogenously tagged proteins, I identified eight hnRNPs that are expressed in GSCs. Due to their unique expression patterns indicating involvement in oogenesis, I selected three hnRNPs of major interest. To test whether three of these hnRNPs, Hrb27C, glo and nonA, were necessary for GSC self-renewal, I used the Gal4/UAS RNAi system to individually knockdown expression of the hnRNPs in the germline. Hrb27C, glo, and nonA are required for a proper number of GSCs. NonA is specifically required for proper GSC establishment. The highly conserved nature of genetic machinery between humans and Drosophila may aid in understanding how the mammalian homologs of Hrb27C, glo, and nonA regulate stem cells in humans. Understanding which hnRNPs regulate establishment and maintenance of stem cells may direct future research on the use of stem cells in cancer therapies and regenerative medicine.