# Toll receptors mediate tissue intrinsic surveillance against aberrant cells by detecting cell fate aberrations

## TL;DR

Toll receptors help tissues detect and eliminate abnormal cells by comparing neighboring cell identities, linking development and tissue health.

## Contribution

Long Toll receptors are identified as mediators of interface surveillance through cell fate comparisons.

## Key findings

- Differences in long Toll receptor levels between adjacent cells trigger interface surveillance.
- Long Toll receptors generate a combinatorial cell-surface code regulated by patterning pathways.
- Interface surveillance operates independently of NF-κB signaling, relying on actomyosin dynamics.

## 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.

Summary: Comparing neighboring cell identities using a Toll-like receptor-based system reveals how tissues sense and remove abnormal cells, thereby linking developmental patterns to tissue health.