AUTHOR=Requena T. , Keder A. , zur Lage P. , Albert J. T. , Jarman A. P. 

TITLE=A Drosophila model for Meniere’s disease: Dystrobrevin is required for support cell function in hearing and proprioception

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.1015651

DOI=10.3389/fcell.2022.1015651

ISSN=2296-634X

ABSTRACT=<p>Meniere’s disease (MD) is an inner ear disorder characterised by recurrent vertigo attacks associated with sensorineural hearing loss and tinnitus. Evidence from epidemiology and Whole Exome Sequencing (WES) suggests a genetic susceptibility involving multiple genes, including α-Dystrobrevin (<italic>DTNA</italic>). Here we investigate a <italic>Drosophila</italic> model. We show that mutation, or knockdown, of the <italic>DTNA</italic> orthologue in <italic>Drosophila</italic>, <italic>Dystrobrevin</italic> (<italic>Dyb</italic>), results in defective proprioception and impaired function of Johnston’s Organ (JO), the fly’s equivalent of the inner ear. <italic>Dyb</italic> and another component of the dystrophin-glycoprotein complex (DGC), <italic>Dystrophin</italic> (<italic>Dys</italic>), are expressed in support cells within JO. Their specific locations suggest that they form part of support cell contacts, thereby helping to maintain the integrity of the hemolymph-neuron diffusion barrier, which is equivalent to a blood-brain barrier. These results have important implications for the human condition, and notably, we note that <italic>DTNA</italic> is expressed in equivalent cells of the mammalian inner ear.</p>