Mechanosensory neuron regeneration in adult Drosophila

Development. 2021 Mar 10;148(5):dev187534. doi: 10.1242/dev.187534.

Abstract

Auditory and vestibular mechanosensory hair cells do not regenerate following injury or aging in the adult mammalian inner ear, inducing irreversible hearing loss and balance disorders for millions of people. Research on model systems showing replacement of mechanosensory cells can provide mechanistic insights into developing new regenerative therapies. Here, we developed lineage tracing systems to reveal the generation of mechanosensory neurons in the Johnston's organ (JO) of intact adult Drosophila, which are the functional counterparts to hair cells in vertebrates. New JO neurons develop cilia and target central brain circuitry. Unexpectedly, mitotic recombination clones point to JO neuron self-replication as a likely source of neuronal plasticity. This mechanism is further enhanced upon treatment with experimental and ototoxic compounds. Our findings introduce a new platform to expedite research on mechanisms and compounds mediating mechanosensory cell regeneration, with nascent implications for hearing and balance restoration.

Keywords: Auditory neuron; In vivo imaging; Lineage tracing; Nervous system; Regeneration; Vestibular neuron.

Publication types

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

MeSH terms

  • Animals
  • Brain / growth & development
  • Brain / metabolism
  • Brain / physiology
  • Cell Lineage
  • Cell Proliferation
  • Cisplatin / pharmacology
  • Drosophila / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Female
  • Male
  • Mechanoreceptors / physiology*
  • Neurogenesis
  • Neuronal Plasticity
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / physiology*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Regeneration / drug effects
  • Temperature

Substances

  • Drosophila Proteins
  • Recombinant Fusion Proteins
  • Cisplatin