LncRNA modulates Dpp-mediated wing development to influence flight in Aedes aegypti

The flight capability of Aedes aegypti underpins global spread of vector-borne diseases (e.g., dengue, Zika, chikungunya), making it a key control target. Decapentaplegic (Dpp), evolutionarily conserved in insect morphogenesis, has unclear spatiotemporal regulatory networks in Ae. aegypti wing bud/haltere development. Here, we identify a wing bud/haltere-specific long non-coding RNA (lncRNA), AAEL025449, forming a competing endogenous RNA (ceRNA) axis to regulate Dpp-mediated development. Spatially, AAEL025449 acts as a microRNA-281 (miR-281) sponge, relieving Dpp transcriptional repression in wing buds. Temporally, it tunes Dpp dynamics during critical apoptosis windows, enabling Dpp to modulate apoptotic timing via the canonical c-Jun N-terminal kinase (JNK) pathway. Disruption of this axis results in shorter wings, indirectly compromising flight capacity and reducing mating success, thereby linking molecular perturbations to fitness-related traits. Additionally, it further clarifies the key temporal-spatial nodes where Dpp regulates wing bud cell apoptosis via JNK, with the spatial node differing from conventional Dpp regulation of wing bud development and manifesting as a gradient diffusion from anterior to posterior wing bud margin during the critical apoptosis period in Ae. aegypti. Our study uncovers a novel spatiotemporal regulatory mechanism for wing bud plasticity, advancing insights into insect wing bud adaptive evolution. This ceRNA axis provides a foundation for selecting targets to suppress mosquito populations and mitigate disease transmission.