ZFIN ID: ZDB-PUB-160522-3
Cilia-Associated Genes Play Differing Roles in Aminoglycoside-Induced Hair Cell Death in Zebrafish
Stawicki, T.M., Hernandez, L., Esterberg, R., Linbo, T., Owens, K.N., Shah, A.N., Thapa, N., Roberts, B., Moens, C.B., Rubel, E.W., Raible, D.W.
Date: 2016
Source: G3 (Bethesda)   6(7): 2225-35 (Journal)
Registered Authors: Linbo, Tor, Moens, Cecilia, Owens, Kelly, Raible, David, Stawicki, Tamara
Keywords: aminoglycosides, cilia, hair cells, intraflagellar transport, transition zone
MeSH Terms:
  • Aminoglycosides/toxicity*
  • Animals
  • Cell Death
  • Cilia/drug effects*
  • Cilia/metabolism
  • Cilia/ultrastructure
  • Cytoplasmic Dyneins/genetics
  • Cytoplasmic Dyneins/metabolism
  • Drug Tolerance/genetics*
  • Gene Expression
  • Hair Cells, Auditory/cytology
  • Hair Cells, Auditory/drug effects*
  • Hair Cells, Auditory/metabolism
  • Mechanotransduction, Cellular
  • Microtubule-Associated Proteins/genetics
  • Microtubule-Associated Proteins/metabolism
  • Mutation*
  • Vesicular Transport Proteins/genetics
  • Vesicular Transport Proteins/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 27207957 Full text @ G3 (Bethesda)
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.