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G3 (Bethesda). 2016 Jul 7;6(7):2225-35. doi: 10.1534/g3.116.030080.

Cilia-Associated Genes Play Differing Roles in Aminoglycoside-Induced Hair Cell Death in Zebrafish.

Author information

1
Department of Biological Structure, University of Washington, Seattle, Washington 98195 Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, Washington 98195.
2
Department of Biological Structure, University of Washington, Seattle, Washington 98195.
3
Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, Washington 98195 Department of Otolaryngology, Head and Neck Surgery, University of Washington, Seattle, Washington, 98195.
4
Department of Biological Structure, University of Washington, Seattle, Washington 98195 Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, Washington 98195 Department of Otolaryngology, Head and Neck Surgery, University of Washington, Seattle, Washington, 98195.
5
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109.
6
Department of Biological Structure, University of Washington, Seattle, Washington 98195 Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, Washington 98195 draible@uw.edu.

Abstract

Hair cells possess a single primary cilium, called the kinocilium, early in development. While the kinocilium is lost in auditory hair cells of most species it is maintained in vestibular hair cells. It has generally been believed that the primary role of the kinocilium and cilia-associated genes in hair cells is in the establishment of the polarity of actin-based stereocilia, the hair cell mechanotransduction apparatus. Through genetic screening and testing of candidate genes in zebrafish (Danio rerio) we have found that mutations in multiple cilia genes implicated in intraflagellar transport (dync2h1, wdr35, ift88, and traf3ip), and the ciliary transition zone (cc2d2a, mks1, and cep290) lead to resistance to aminoglycoside-induced hair cell death. These genes appear to have differing roles in hair cells, as mutations in intraflagellar transport genes, but not transition zone genes, lead to defects in kinocilia formation and processes dependent upon hair cell mechanotransduction activity. These mutants highlight a novel role of cilia-associated genes in hair cells, and provide powerful tools for further study.

KEYWORDS:

aminoglycosides; cilia; hair cells; intraflagellar transport; transition zone

PMID:
27207957
PMCID:
PMC4938675
DOI:
10.1534/g3.116.030080
[Indexed for MEDLINE]
Free PMC Article

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