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

Epithelial morphogenesis generates complex tissue architectures with remarkable reproducibility, yet how such self-organized shape transformations 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 remodeling of the basal extracellular matrix (ECM) by neighboring tissues. Live imaging analyses reveal a previously unrecognized epithelial shape transition at the larval-to-pupal stage, in which the wing disc epithelium transforms from a concave to a convex configuration. Rather than being driven autonomously by the epithelium, this morphogenetic transition depends on adjacent non-epithelial cell populations, including myoblasts and tracheal cells. Mechanistically, systemic ecdysone signaling activates Mmp1 and Mmp2 in these neighboring tissues, leading to spatially restricted basal ECM disassembly that permits collective epithelial shape reorganization. Together, our findings establish ECM remodeling at tissue interfaces as a non-autonomous regulatory layer that enables epithelial self-organization during development.