Adult stem cells respond to environmental signals, such as diet, to properly maintain tissues; however, the mechanisms involved are largely unknown. The Drosophila ovary is a stem cell-based tissue that responds dramatically to diet, has a well-defined cell biology and is one of the premier systems for the study of stem cell regulation in vivo. In this thesis I examine the roles of insulin and Target of rapamycin (TOR) signaling in regulating Drosophila ovarian stem cell proliferation and maintenance, and the growth, proliferation, and survival of their progeny. Although insulin and TOR signaling both play cell-specific roles in regulating how stem cells and their progeny respond to diet, evidence suggests that other factors, potentially from fat cells, are also required. One potential mechanism by which fat cells may communicate nutritional status to the ovary is via adipokine-like signaling. In mammals, the adipokine adiponectin binds its receptors on peripheral tissues, sensitizing them to insulin signaling. Drosophila has an adiponectin receptor (dAdipoR) homolog that, according to my preliminary results, appears to have a cell-autonomous, diet-dependent role in regulating GSC maintenance and the proliferation of their progeny. Furthermore, fat-cell knockdown of dAdipoR increases the number of divisions during germline cyst formation, suggesting that dAdipoR-mediated signaling in multiple tissues modulates oogenesis. To identify potential dAdipoR ligands and/or additional fat cell factors that link fat cell nutrient-sensing to ovarian stem cell regulation, I took a quantitative proteomics approach to identify fat cell secreted proteins regulated by diet. A fat cell-specific RNAi assay will be used to determine which fat body secreted candidates have a role in ovarian stem cell regulation. These studies provide key insights into the highly conserved regulatory mechanisms that control the stem cell response to diet and suggest that multiple factors, likely from multiple tissues, together act to coordinate stem cell activity with the nutritional demands of an organism.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-11292010-123006 |
| Date | 06 December 2010 |
| Creators | LaFever, Leesa Marie |
| Contributors | Chin Chiang, Ph.D., Laura Lee, MD PhD, Lila Solnica-Krezel, PhD, Jim Goldenring, MD PhD, Daniela Drummond-Barbosa, PhD |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-11292010-123006/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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