In multi-cellular organisms, cell competition serves as a quality control machinery to eliminate suboptimal cells and to maximize tissue fitness. Failure of this process has been implicated in conditions as diverse as aging and tumor progression. The phenomenon and some of the mechanisms underlying cell competition are conserved from Drosophila to mammals. Cell competition occurs both within tissue primordia and also among adult stem cells, which function to maintain organismal homeostasis. Most adult stem cells reside in a specific microenvironment, called a niche, that both anchors the stem cell and produces signals to ensure continued stem cells maintenance. While adult stem cells compete with each other for niche anchorage and niche signaling, the relationship between niche secreted maintenance signals and stem cell competition is poorly understood. In this thesis, I used Drosophila female Germline Stem Cells (GSCs) as a model system to study whether the GSC maintenance factors, members of the Bone Morphogenetic Protein (BMP) family, also play a role in GSC competition. I demonstrated that differential BMP signaling between neighboring GSCs directly triggers stem cell competition. My data indicate that there are two thresholds for controlling distinct GSCs behaviors. A very low level of BMP signaling in GSCs is necessary to maintain the GSCs in an undifferentiated state, irrespective of the state of neighboring GSCs. A second, higher threshold of BMP signaling is involved in GSC competition. In between these two thresholds, a single GSC will be outcompeted by a GSC with wild-type signaling, but will be maintained if all other GSCs have a similar level of signaling. Thus, an absolute low value of BMP signaling is necessary for GSC maintenance, while differences in BMP signaling between GSCs serve as a read out of the relative fitness of the GSC. GSC competition may have important evolutionary implications, as GSC fitness can be markedly affected by novel germline mutations that could have deleterious consequences for future generations.




Downloads Statistics

Download Full History