Alexander Ahl, Petra Zur Lage, Andrew Jarman Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UKWhilst sensory neurons of the inner ear are remarkably resilient, they are unfortunately subjected to ‘wear and tear’, that reduce their performance and lifespan. Hearing sensitivity in both insects and vertebrates occurs via unique mechanosensory cells that are specialised for auditory transduction. Analogous to the stereo cilia hair cells of the human ear are the cilium bearing chordotonal neurons of Drosophila melanogaster, that offer a compelling paradigm to investigate genetic and molecular constituents during auditory apparatus development. Transcriptome analysis of Drosophila chordotonal sensory neurons has revealed a 25.7 fold up-regulation in the expression of the gene CG6980 during development (Cachero et al. 2011). CG6980 is the Drosophila orthologue of the human tetratricopeptide repeat gene TTC12, proposed to mediate protein-protein interactions. We demonstrate that in situ expression of CG6980 in wildtype Drosophila embryos is exclusive to auditory neurons, and is dependent on the transcription factors governing auditory neuron sensory differentiation. CG6980 CRISPR/Cas9 deletion mutants exhibit defects in both chordotonal sensory neurons and sperm cells, indicated by diminished proprioception and immotile sperm, rendering male flies infertile. Electron microscopy of chordotonal cilia in the antennae and sperm cell flagella reveal a loss of dynein motor arm complexes and disruption of the axoneme structure in the sperm, but not in the antennae, the latter might be explained by redundancy with a related gene, CG34297. Together, findings lead us to hypothesize that TTC12 functions as a molecular co-chaperone during motor protein assembly in motile cilia, and may be a novel candidate gene for human primary cilia dyskinesia.ReferencesCachero, S. et al., 2011. The Gene Regulatory Cascade Linking Proneural Specification with Differentiation in Drosophila Sensory Neurons. PLoS Biology, 9(1), p.e1000568.Funded by: Zhejiang University Career Development PhD Scholarship in the Deanery of Biomedical Sciences* entered into the PhD student poster competition This article was published on 2024-12-13
