Extrinsic MMPs drive epithelial shape change via basal extracellular matrix disassembly in the Drosophila wing disc

Epithelial morphogenesis generates complex tissue architectures with remarkable reproducibility, yet how tissue-scale epithelial curvature transitions are triggered in vivo remains poorly understood. Here, we show that epithelial morphogenesis during early pupal development of the Drosophila wing disc is regulated non-autonomously through spatially restricted remodeling of the basal extracellular matrix (ECM) by neighboring tissues. Live imaging analyses reveal a previously unrecognized morphogenetic event at the larval-to-pupal stage, in which the wing disc epithelium undergoes a concave-to-convex curvature inversion. This curvature inversion is preceded by local loss of Collagen IV from the basal ECM, particularly in the notum and hinge regions. Rather than being driven autonomously by the epithelium, the shape change depends on adjacent non-epithelial cell populations, including myoblasts and tracheal cells, whose dynamic behaviors are spatially and temporally associated with basal ECM disassembly. Mechanistically, systemic ecdysone signaling activates Mmp1 and Mmp2 in these neighboring tissues, leading to localized basal ECM disassembly that permissively enables epithelial self-organization. Together, our findings identify extrinsic ECM remodeling at tissue interfaces as a non-autonomous regulatory layer that spatially licenses tissue-scale epithelial curvature transitions during development.