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

PLoS Genet. 2020 Aug 7;16(8):e1008942. doi: 10.1371/journal.pgen.1008942. eCollection 2020 Aug.

Abstract

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. Drosophila class IV dendrite arborization (C4da) sensory neurons regenerate adult-specific dendrites after eliminating larval dendrites during metamorphosis. Here we show that the microRNA miR-87 is a critical regulator of dendrite regeneration in Drosophila. miR-87 knockout impairs dendrite regeneration after developmentally-programmed pruning, whereas miR-87 overexpression in C4da neurons leads to precocious initiation of dendrite regeneration. Genetic analyses indicate that the transcriptional repressor Tramtrack69 (Ttk69) is a functional target for miR-87-mediated repression as ttk69 expression is increased in miR-87 knockout neurons and reducing ttk69 expression restores dendrite regeneration to mutants lacking miR-87 function. We further show that miR-87 is 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 that miR-87 promotes dendrite regrowth during regeneration at least in part through suppressing Ttk69 in Drosophila sensory neurons and suggest that developmental and injury-induced dendrite regeneration share a common intrinsic mechanism to reactivate dendrite growth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendrites / genetics
  • Dendrites / physiology
  • Drosophila Proteins / genetics*
  • Drosophila melanogaster / genetics
  • Gene Expression Regulation, Developmental
  • Larva / genetics
  • Larva / growth & development
  • Metamorphosis, Biological / genetics*
  • MicroRNAs / genetics*
  • Nerve Regeneration / genetics*
  • Repressor Proteins / genetics*
  • Sensory Receptor Cells / metabolism

Substances

  • Drosophila Proteins
  • MicroRNAs
  • Repressor Proteins
  • ttk protein, Drosophila