Drosophila miR-87 promotes dendrite regeneration by targeting the transcriptional repressor Tramtrack69

To remodel functional neuronal connectivity, neurons often alter dendrite arbors through elimination and subsequent regeneration of dendritic branches. However, the intrinsic mechanisms underlying this developmentally programmed dendrite regeneration and whether it shares common machinery with injury-induced regeneration remain largely unknown.Drosophilaclass IV dendrite arborization (C4da) sensory neurons regenerate adult-specific dendrites after eliminating larval dendrites during metamorphosis. Here we show that the microRNAmiR-87is a critical regulator of dendrite regeneration inDrosophila.miR-87knockout impairs dendrite regeneration after developmentally-programmed pruning, whereasmiR-87overexpression in C4da neurons leads to precocious initiation of dendrite regeneration. Genetic analyses indicate that the transcriptional repressor Tramtrack69 (Ttk69) is a functional target formiR-87-mediated repression asttk69expression is increased inmiR-87knockout neurons and reducingttk69expression restores dendrite regeneration to mutants lackingmiR-87function. We further show thatmiR-87is required for dendrite regeneration after acute injury in the larval stage, providing a mechanistic link between developmentally programmed and injury-induced dendrite regeneration. These findings thus indicate thatmiR-87promotes dendrite regrowth during regeneration at least in part through suppressing Ttk69 inDrosophilasensory neurons and suggest that developmental and injury-induced dendrite regeneration share a common intrinsic mechanism to reactivate dendrite growth. Author summary Dendrites are the primary sites for synaptic and sensory inputs. To remodel or repair neuronal connectivity, dendrites often exhibit large-scale structural changes that can be triggered by developmental signals, alterations in sensory inputs, or injury. Despite the importance of dendritic remodeling to nervous system function, the molecular basis for this remodeling is largely unknown. Here we used an unbiased genetic screen andin vivoimaging inDrosophilasensory neurons to demonstrate that the microRNAmiR-87is a critical factor required in neurons to reactivate dendritic growth both in developmental remodeling and following injury. Our work supports the model thatmiR-87promotes dendrite regeneration by blocking expression of the transcriptional repressor Tramtrack69 in neurons. This study thus establishes a role for miRNAs in temporal control of dendrite regeneration.