Editors' ChoiceGenetics

Fruit Flies Create a Buzz About Hearing

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Science Translational Medicine  19 Sep 2012:
Vol. 4, Issue 152, pp. 152ec170
DOI: 10.1126/scitranslmed.3004933

“Forgive me when you see me draw back, when I would have gladly mingled with you,” remarked composer Ludwig von Beethoven when addressing the social implications of hearing loss—the most common sensory deficit in humans. Despite the discovery of dozens of genes implicated in the pathogenesis of impaired hearing, the causes of many cases of hereditary hearing loss are unknown. Now, Senthilan et al. study the genetics of hearing in the fruit fly Drosophila melanogaster, a powerful genetically amenable model system for studying complex biological processes of higher organisms.

To identify genes that potentially participate in the hearing process, the authors conducted gene expression profiling by isolating RNA from the hearing apparatus of Drosophila. The Johnston organ comprises a portion of the hearing machinery and consists of key neurons and components that are essential for Drosophila hearing. By comparing the gene expression profiles of flies with and without a Johnston organ, Senthilan and colleagues identified 274 putative hearing-related genes. The authors then performed loss-of-function (LOF) experiments, individually knocking out 42 of these genes to assess their role in hearing by exposing the flies to pure tones and measuring the activation of the antennal nerve. The phenotypes generated by the LOF studies varied from subtle to profound hearing loss, mimicking the clinical spectrum seen in humans; in fact, mutation of one gene even enhanced hearing. Of the 42 genes analyzed, 27 altered the flies’ response to sound. This outcome effectively doubled the number of known genes that play a role in hearing in Drosophila.

Despite the fact that flies and people are evolutionarily quite divergent, 89 of the 274 Drosophila genes have homologs in vertebrates such as mice and humans. As a kind of proof of concept for the translational relevance of the fly study findings, several of the newly identified genes were previously implicated in human hearing. Researchers can now study the biology of the products of the various candidate genes to determine whether and how they function in permitting human subjects to hear. Although much work remains to be done before therapies that target the relevant proteins and pathways can be developed, this study provides the framework for such research.

P. R. Senthilan et al., Drosophila auditory organ genes and genetic hearing defects. Cell 150, 1042–1054 (2012). [Abstract]

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