PUBLICATION

Mutations in cadherin 23 affect tip links in zebrafish sensory hair cells

Authors
Söllner, C., Rauch, G-J., Siemens, J., Geisler, R., Schuster, S.C., The Tübingen 2000 Screen Consortium, Müller, U., and Nicolson, T.
ID
ZDB-PUB-040402-1
Date
2004
Source
Nature   428(6986): 955-959 (Journal)
Registered Authors
Geisler, Robert, Nicolson, Teresa, Rauch, Gerd-Jörg, Söllner, Christian
Keywords
none
MeSH Terms
  • Alleles
  • Animals
  • Cadherins/genetics
  • Cadherins/metabolism*
  • Cilia/metabolism
  • Cilia/ultrastructure
  • Gene Expression Profiling
  • Hair Cells, Auditory/metabolism*
  • Hair Cells, Auditory/ultrastructure
  • Hearing/genetics
  • Hearing/physiology
  • Larva/genetics
  • Larva/physiology
  • Mechanotransduction, Cellular/genetics
  • Mechanotransduction, Cellular/physiology
  • Mutation/genetics*
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins
PubMed
15057246 Full text @ Nature
Abstract
Hair cells have highly organized bundles of apical projections, or stereocilia, that are deflected by sound and movement. Displacement of stereocilia stretches linkages at the tips of stereocilia that are thought to gate mechanosensory channels. To identify the molecular machinery that mediates mechanotransduction in hair cells, zebrafish mutants were identified with defects in balance and hearing. In sputnik mutants, stereociliary bundles are splayed to various degrees, with individuals displaying reduced or absent mechanotransduction. Here we show that the defects in sputnik mutants are caused by mutations in cadherin 23 (cdh23). Mutations in Cdh23 also cause deafness and vestibular defects in mice and humans, and the protein is present in hair bundles. We show that zebrafish Cdh23 protein is concentrated near the tips of hair bundles, and that tip links are absent in homozygous sputnik(tc317e) larvae. Moreover, tip links are absent in larvae carrying weak alleles of cdh23 that affect mechanotransduction but not hair bundle integrity. We conclude that Cdh23 is an essential tip link component required for hair-cell mechanotransduction.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes