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

Overview

Journal G3 (Bethesda)

Publisher Oxford University Press

Specialties Genetics
Molecular Biology

Date 2016 May 22

PMID 27207957

Citations 18

Authors

Tamara M Stawicki

Liana Hernandez

Robert Esterberg

Tor Linbo

Kelly N Owens

Arish N Shah

Nihal Thapa

Brock Roberts

Cecilia B Moens

Edwin W Rubel

David W Raible

Affiliations

Soon will be listed here.

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.

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