Notch signaling controls Drosophila female germline stem cell competitiveness for niche occupancy. Tseng Cheng-Yuan^1,2*, Hsu Hwei-Jan^1,2. 1) Institution of Cellular and Oragnismic Biology, Academia Sinica, Taipei, Taiwan; 2) Institution of Life Sciences, National Defense Medical Center, Taipei, Taiwan.

   Stem cells reside in a specialized microenvironment, or niche, which provides physical contact mediated by cell-cell adhesion molecules, and secretes factors that regulate stem cells. We have previously shown that insulin signaling directly controls germline stem cell (GSC) division via FOXO. In addition, insulin levels regulate Notch activation to maintain GSC niche via the effect of FOXO on transcription of fringe (fng), which encodes a glycosyltransferase that modulates Notch glycosylation. It is not clear, however, if insulin levels also control GSC division via the same mechanism observed in the niche. To address this, we disrupted Notch signaling in GSCs by generating fng and Notch mutant GSCs. We evidenced that their division and maintenance were not affected, indicating that insulin/FOXO-mediated signaling controls GSC division independently of Notch signaling in GSCs. Surprisingly, these mutant GSCs tended to push wild-type GSCs away from the niche, suggesting that GSCs with low Notch signaling have relative higher competitiveness for niche occupancy. The self-renewal-promoting BMP niche signal and GSC-niche adhesive molecule, E-cadherin, are the only factors known to control female GSC competition. Interestingly, we found that BMP signaling was not affected in fng and Notch mutant GSCs, while E-cadherin expression at the junction between these GSCs and their niche was significantly increased. These results indicate that Fringe-mediated Notch signaling controls GSC competiveness for niche occupancy through E-cadherin.Our results uncover a novel function of Notch signaling in stem cell competition, which may serve as a quality control to keep good stem cells in the niche. These results also provide insights into how stem cells communicate with each other, and how stem cells interact with their niche to ensure the integrity of tissue function.