Using Drosophila to study mechanisms of hereditary hearing loss.

Tongchao Li,Andrew K Groves,Hugo J Bellen

doi:10.1242/dmm.031492

Abstract

ABSTRACTJohnston's organ – the hearing organ of Drosophila – has a very different structure and morphology to that of the hearing organs of vertebrates. Nevertheless, it is becoming clear that vertebrate and invertebrate auditory organs share many physiological, molecular and genetic similarities. Here, we compare the molecular and cellular features of hearing organs in Drosophila with those of vertebrates, and discuss recent evidence concerning the functional conservation of Usher proteins between flies and mammals. Mutations in Usher genes cause Usher syndrome, the leading cause of human deafness and blindness. In Drosophila, some Usher syndrome proteins appear to physically interact in protein complexes that are similar to those described in mammals. This functional conservation highlights a rational role for Drosophila as a model for studying hearing, and for investigating the evolution of auditory organs, with the aim of advancing our understanding of the genes that regulate human hearing and the pathogenic mechanisms that lead to deafness.

Highlights

Hearing loss is one of the most common neurological disorders in humans, affecting 2 to 3 of every 1000 children in the USA (Imtiaz et al, 2016; Naz et al, 2017)
We suggest that by improving our understanding of the mechanisms of hearing in Drosophila, we could discover new genes required for hair cell function in vertebrates, better understand the evolution of auditory organs, and gain new insights into the pathogenic mechanisms of some deafness-related genes
The National Institutes of Health (NIH)-funded Undiagnosed Diseases Network seeks to find possible genetic etiologies for rare human diseases (Wangler et al, 2017), some of which include hearing loss, and it is likely that this initiative will reveal new forms of syndromic hearing loss

Summary

Introduction

Hearing loss is one of the most common neurological disorders in humans, affecting 2 to 3 of every 1000 children in the USA (Imtiaz et al, 2016; Naz et al, 2017). As the basilar membrane vibrates, the motion of the organ of Corti causes the stereociliary bundles of the hair cells to be displaced by contact with the tectorial membrane (outer hair cells) or fluid flow (inner hair cells) This opens mechanically gated ion channels in the tips of the stereocilia (Corey and Holt, 2016; Fettiplace, 2016; Wu and Muller, 2016). Despite the structural differences between insect and vertebrate sound-detecting cells, molecular evidence suggests that certain aspects of the development of the various cell types found in auditory organs are conserved between invertebrates and vertebrates (Bechstedt and Howard, 2008; Bokolia and Mishra, 2015; Caldwell in Drosophila as a proneural gene required for the formation of and Eberl, 2002; Lewis and Steel, 2012) (Table 1). In Drosophila, the loss of ato leads to loss of all chordotonal

C Stereocilia tip links of a hair cell in mammalian cochlea

Findings

Conclusion