Hbs and Rst adhesion molecules provide a regional code that regulates cell elimination during epithelial remodeling

Cellular interactions and mechanical forces are fundamental in shaping epithelial tissue architecture. In the <i>Drosophila</i> notum, tissue compression at the midline promotes epithelial cell elimination. Here, we conducted a multi-step RNAi screen and identified 47 diverse regulators of notum epithelial remodeling. We find that the two cell adhesion proteins Hibris (Hbs) and Roughest (Rst) show high expression in zones of cell survival versus low levels in areas of cell pruning. Notum-wide knock-down of <i>hbs</i> or <i>rst</i> or homogenous <i>hbs</i> overexpression disrupts cell death patterns and results in adult tissue malformations. Local suppression of Hbs and Rst in Hbs^high/Rst^high territories triggers ectopic cell elimination indicating that Hbs/Rst can instruct cell removal. Interestingly, Hbs but not Rst is regulated by compaction-sensitive EGFR signaling, positioning Hbs as an integrator of both mechanical and cell property cues. These findings uncover a novel adhesive landscape that shapes the thorax midline and potentially other organs.