Diverse Roles of Axonemal Dyneins in Drosophila Auditory Neuron Function and Mechanical Amplification in Hearing

abstract: ...Much like vertebrate hair cells, the chordotonal sensory neurons that mediate hearing in Drosophila are motile and amplify the mechanical input of the ear. Because the neurons bear mechanosensory primary cilia whose microtubule axonemes display dynein arms, we hypothesized that their motility is powered by dyneins. Here, we describe two axonemal dynein proteins that are required for Drosophila auditory neuron function, localize to their primary cilia, and differently contribute to mechanical amplification in hearing. Promoter fusions revealed that the two axonemal dynein genes Dm dnah3 (= CG17150 ) and Dm dnai2 (= CG6053 ) are expressed in chordotonal neurons, including the auditory ones in the flys ear. Null alleles of both dyneins equally abolished electrical auditory neuron responses, yet whereas mutations in Dm dnah3 facilitated mechanical amplification, amplification was abolished by mutations in Dm dnai2 . Epistasis analysis revealed that Dm dnah3 acts downstream of Nan-Iav channels in controlling the amplificatory gain. Dm dnai2 , in addition to being required for amplification, was essential for outer dynein arms in auditory neuron cilia. This establishes diverse roles of axonemal dyneins in Drosophila auditory neuron function and links auditory neuron motility to primary cilia and axonemal dyneins. Mutant defects in sperm competition suggest that both dyneins also function in sperm motility.

... input of the ear. Because the neurons bear mechanosensory primary cilia whose microtubule axonemes display dynein arms, we hypothesized that their motility is powered by dyneins. Here, we describe two axonemal dynein proteins that are required for Drosophila auditory neuron function, localize to their primary cilia, and differently contribute to mechanical amplification in hearing. Promoter fusions revealed that the two axonemal dynein genes Dm dnah3 (= CG17150 ) and Dm dnai2 (= CG6053 ) are expressed in chordotonal neurons, including the auditory ones in the flys ear. Null alleles of both dyneins equally abolished electrical auditory neuron responses, yet whereas mutations in Dm dnah3 facilitated mechanical amplification, amplification was abolished by mutations in Dm dnai2 . Epistasis analysis revealed that Dm dnah3 acts downstream of Nan-Iav channels in controlling the amplificatory gain. Dm dnai2 , in addition to being required for amplification, was essential for outer dynein arms in

... auditory neuron function and mechanical amplification in fly hearing. Results Dm DNAH3 is a monomeric dynein heavy chain CG17150 is one of eleven axonemal dynein heavy chain genes in Drosophila 28 29 ( Fig. S1 ). It falls into the IAD-3 (inner-arm dynein-3) subgroup, described as inner arm-associated and single-headed (monomeric), together with the Drosophila Dhc62B / CG15804 and Dhc36C/CG5526 and human DNAH3 and DNAH7 gene products 28 29 . Among the human dynein heavy chains, CG17150 is most similar (50% amino acid identity) to DNAH3, and we name the gene Dm dnah3 for this orthology. The IAD-3 heavy chain subgroup has several representatives in each ciliated species, but information about their function is scant. A mutation of Chlamydomonas that deletes most of an IAD-3 heavy chain (DHC9) lacks a dynein inner arm and shows reduced flagellar beat frequency, especially in more viscous media, suggesting that this motor is important for motility under load 31 . Dm DNAI2 is an outer arm IC2

... the male germline. Dm dnah3 and Dm dnai2 are expressed in chordotonal neurons To characterize the cellular expression patterns of Dm dnah3 and Dm dnai2 , we generated fusions between the Dm dnah3 or Dm dnai2 enhancer/promoter regions and the yeast transcription activator GAL4 (see Supplementary Methods ). To visualize GAL4 expression, transgenic flies expressing Dm dnah3 -GAL4 and Dm dnai2- GAL4 were crossed to flies expressing a green fluorescent protein (GFP) under the control of upstream activating sequence (UAS) elements (UAS-GFP). GFP signals were enhanced with an anti-GFP antibody, and neurons were counterstained with the monoclonal anti-Futsch antibody 22c10 (Ref. 36 ). Labelling induced by the Dm dnah3 and Dm dnai2 enhancer/promoter regions was observed in Johnstons organ, the chordotonal auditory sensory organ in the flys antenna ( Fig. 1A ). Within this organ, anti-GFP and 22c10 staining superimposed, documenting that virtually all its 500 sensory neurons express Dm dnah3 and Dm dnai2 ( Fig. 1A ). Apart from Johnstons organ neurons, expression of Dm dnah3 and Dm dnai2 was also observed in other chordotonal neurons, including those of the femoral chordotonal organ (FCO) in the flys leg and those of the larval pentascolopidial organ (lch5) ( Fig. 1B ). No expression was seen in the central nervous system or ciliated chemoreceptors and mechanosensory bristle neurons whose cilia reportedly lack dynein arms 7 . Chordotonal sensory neurons thus seem to be the only Drosophila

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Gene: DNAH3 - dynein, axonemal, heavy chain 3 - (NCBI)

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