Abstract
Tissue-intrinsic surveillance systems maintain tissue health by detecting and eliminating aberrant cells. One such mechanism, interface surveillance, is activated by differences in cell fate programs between neighboring cells, leading to actomyosin accumulation, JNK-signaling and apoptosis at these interfaces. Here, we identify long Toll receptors (Toll-2, Toll-6, Toll-7 and Toll-8) as mediators of interface surveillance in Drosophila imaginal discs. Using genetic mosaics and mapping of expression pattern, we show that differences in long Toll receptor levels between adjacent cells are sufficient to induce all hallmarks of interface surveillance. This response relies on the comparison of relative expression levels set by fate-specifying pathways and is thus position dependent. Specifically, long Toll receptor expression is regulated by multiple patterning pathways, generating a combinatorial cell-surface code that is disrupted in developmentally aberrant or oncogenic cells. Notably, interface surveillance functions independently of NF-κB signaling, rather reflecting a role for long Toll receptors in modulating cell affinity through actomyosin dynamics. Our findings reveal long Toll receptors as integrators of developmental patterning and tissue homeostasis, and provide insights into how tissues detect and respond to aberrant or oncogenic mutations.
