Mechanosensory neuron regeneration in adult Drosophila

Abstract

Auditory and vestibular mechanosensory hair cells in the adult mammalian inner ear do not regenerate following injury or ageing, inducing irreversible hearing loss and balance disorders for millions of people. Research on model systems showing replacement of mechanosensory cells can provide mechanistic insight to develop new regenerative therapies. Here we developed new lineage tracing systems to reveal the generation of mechanosensory neurons (Johnston's Organ, JO) in the antennae of intact adult Drosophila. New JO neurons develop cilia, express an essential mechano-transducer gene and target central brain circuitry. Furthermore, we identified low-level JO self-replication as a new mechanism of neuronal plasticity. Overall, our findings introduce a new platform to expedite the research of mechanisms and compounds mediating mechanosensory cell regeneration.

Olfactory neuron turnover in adultDrosophila

“…Finally, we compared adult neurogenesis in the olfactory system with that occurring in other sensory systems. New neurons have also been detected by P-MARCM in the visual and auditory/vestibular system of 3 week-old adult flies (Fernández-Hernández et al, 2019) (Supplementary Figure 1A-C). A comparative analysis across the 3 sensory systems reveals the highest rate of neurogenesis in the olfactory system of the third antennal segment (41.0+/-2.8 SEM OSN/antenna, ~3% of ~1300 total OSN per antenna,100% antennae (n=14), this work), followed by the mechanosensory auditory/vestibular JO neurons in the second antennal segment (11.2 JO neurons/antenna, ~2.2% of ~500 JO neurons per antenna, interpolation for 3 weeks from 2 weeks (n=7) and 4 weeks (n=7) timepoints, 50% of antennae analyzed), and lastly by the projection neurons in the medulla of the optic lobes 31.0+/- 2.4 SEM neurons per optic lobe, ~0.1% of ~40,000 interneurons, 100% optic lobes analyzed (n=12), (Fernández-Hernández et al, 2019) (Supplementary Figure 1D).…”

“…We recently developed P-MARCM, a permanently-active lineage tracing system to label mitotically-derived cells in adult Drosophila tissues, including those appearing at low frequency, in a cell type-specific manner (Fernández-Hernández et al, 2019). Briefly, in this method, sustained expression of the recombinase FLP triggered by a heat shock (HS) mediates recombination of homologous chromosomes at G2 phase, allowing expression of cytoplasmic GFP and nuclear RFP in hemiclones of daughter cells upon mitosis.…”

“…We next asked whether new OSN detected by P-MARCM might replace lost ones in an ongoing turnover process, as it’s been suggested for the Johnston’s Organ (Fernández-Hernández et al, 2019). To answer this, we expressed the genetically-encoded reporter of apoptosis UAS-GC3Ai (GFP sensor Caspase-3-like protease Activity indicator (Schott et al, 2017)) with the pan-neuronal nsyb-GAL4 driver.…”

“…We next asked whether new OSN detected by P-MARCM might replace lost ones in an ongoing turnover process, as it's been suggested for the Johnston's Organ (Fernández-Hernández et al, 2019).…”

“…We recently developed a modified lineage tracing system to detect generation of neurons in the optic lobes and the mechanosensory systemin the antennae of adult flies (Fernández-Hernández et al, 2019). We therefore hypothesized that the olfactory system also retains this capacity.…”