Cell competition employs comparisons of fitness to selectively eliminate cells sensed as less healthy. In Drosophila, apoptotic elimination of the weaker “loser” cells from growing wing discs is ...induced by a signaling module consisting of the Toll ligand Spätzle (Spz), several Toll-related receptors, and NF-κB factors. How this module is activated and restricted to competing disc cells is unknown. Here, we use Myc-induced cell competition to demonstrate that loser cell elimination requires local wing disc synthesis of Spz. We identify Spz processing enzyme (SPE) and modular serine protease (ModSP) as activators of Spz-regulated competitive signaling and show that “winner” cells trigger elimination of nearby WT cells by boosting SPE production. Moreover, Spz requires both Toll and Toll-8 to induce apoptosis of wing disc cells. Thus, during cell competition, Spz-mediated signaling is strictly confined to the imaginal disc, allowing errors in tissue fitness to be corrected without compromising organismal physiology.
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•In Myc super-competition, Spz signals via Toll and Toll-8 to kill loser cells•Spz is activated for competitive signaling by the proteases SPE and ModSP•Regulation of protease production and receptor expression by Myc allows “cheating”•Wing disc-restricted Spz keeps competitive signaling isolated from immune tissues
Low levels of the Toll ligand Spätzle and its activating proteases are synthesized continuously by wing disc cells, but signaling is unproductive. Alpar et al. show that Myc super-competitor cells boost production of the proteases, thereby triggering Spätzle activation and inducing a killing signal that selectively eliminates nearby wild-type cells.
Shape is a conspicuous and fundamental property of biological systems entailing the function of organs and tissues. While much emphasis has been put on how tissue tension and mechanical properties ...drive shape changes, whether and how a given tissue geometry influences subsequent morphogenesis remains poorly characterized. Here, we explored how curvature, a key descriptor of tissue geometry, impinges on the dynamics of epithelial tissue invagination. We found that the morphogenesis of the fold separating the adult Drosophila head and thorax segments is driven by the invagination of the Deformed (Dfd) homeotic compartment. Dfd controls invagination by modulating actomyosin organization and in-plane epithelial tension via the Tollo and Dystroglycan receptors. By experimentally introducing curvature heterogeneity within the homeotic compartment, we established that a curved tissue geometry converts the Dfd-dependent in-plane tension into an inward force driving folding. Accordingly, the interplay between in-plane tension and tissue curvature quantitatively explains the spatiotemporal folding dynamics. Collectively, our work highlights how genetic patterning and tissue geometry provide a simple design principle driving folding morphogenesis during development.
Growing tissues are communities of cells that cooperate to form a robust, functional organ. Cooperative behavior is enforced by cell competition, wherein comparisons of fitness lead to selective ...elimination of cells sensed as relatively less healthy. Elimination of these ‘loser’ cells from Drosophila wing imaginal discs results in cell death induced by deployment of a genetic module consisting of the secreted Toll ligand Spätzle (Spz), several Toll related receptors, and NFkB factors. How signaling by this module is activated and restricted only to competing cells is unknown. Here, we investigate the signaling role of Spz in Myc-induced cell competition. We demonstrate that elimination of wild-type loser cells requires local synthesis and activation of Spz in the wing disc. We identify Spätzle Processing Enzyme (SPE) and Modular Serine Protease (modSP) as upstream mediators of Spz-mediated loser cell elimination, and show that an increase in SPE in ‘winner’ cells is required for Spz to kill loser cells. Finally, we show that Spz requires both Toll and Toll-8 to induce apoptosis of wing disc cells. Our results indicate that during cell competition, Spz-mediated signaling is strictly confined to the imaginal disc, allowing errors in tissue fitness to be corrected without compromising organismal physiology.
Growing tissues are communities of cells that cooperate to form a robust, functional organ. Cooperative behavior is enforced by cell competition, wherein comparisons of fitness lead to selective ...elimination of cells sensed as relatively less healthy. Elimination of these ‘loser’ cells from Drosophila wing imaginal discs results in cell death induced by deployment of a genetic module consisting of the secreted Toll ligand Spätzle (Spz), several Toll related receptors, and NFkB factors. How signaling by this module is activated and restricted only to competing cells is unknown. Here, we investigate the signaling role of Spz in Myc-induced cell competition. We demonstrate that elimination of wild-type loser cells requires local synthesis and activation of Spz in the wing disc. We identify Spätzle Processing Enzyme (SPE) and Modular Serine Protease (modSP) as upstream mediators of Spz-mediated loser cell elimination, and show that an increase in SPE in ‘winner’ cells is required for Spz to kill loser cells. Finally, we show that Spz requires both Toll and Toll-8 to induce apoptosis of wing disc cells. Our results indicate that during cell competition, Spz-mediated signaling is strictly confined to the imaginal disc, allowing errors in tissue fitness to be corrected without compromising organismal physiology.
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