PUBLICATION

The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear

Authors
Colantonio, J.R., Vermot, J., Wu, D., Langenbacher, A.D., Fraser, S., Chen, J.N., and Hill, K.L.
ID
ZDB-PUB-090330-2
Date
2009
Source
Nature   457(7226): 205-209 (Journal)
Registered Authors
Chen, Jau-Nian, Fraser, Scott E., Langenbacher, Adam, Vermot, Julien
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Cilia/metabolism
  • Cilia/physiology*
  • Dyneins/chemistry
  • Dyneins/deficiency
  • Dyneins/genetics
  • Dyneins/metabolism*
  • Epigenesis, Genetic
  • Humans
  • Microscopy, Video
  • Microtubule Proteins/chemistry
  • Microtubule Proteins/deficiency
  • Microtubule Proteins/genetics
  • Microtubule Proteins/metabolism*
  • Molecular Sequence Data
  • Movement*
  • Multiprotein Complexes/deficiency
  • Multiprotein Complexes/genetics
  • Multiprotein Complexes/metabolism
  • Otolithic Membrane/cytology*
  • Otolithic Membrane/embryology*
  • Otolithic Membrane/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
19043402 Full text @ Nature
Abstract
In teleosts, proper balance and hearing depend on mechanical sensors in the inner ear. These sensors include actin-based microvilli and microtubule-based cilia that extend from the surface of sensory hair cells and attach to biomineralized 'ear stones' (or otoliths). Otolith number, size and placement are under strict developmental control, but the mechanisms that ensure otolith assembly atop specific cells of the sensory epithelium are unclear. Here we demonstrate that cilia motility is required for normal otolith assembly and localization. Using in vivo video microscopy, we show that motile tether cilia at opposite poles of the otic vesicle create fluid vortices that attract otolith precursor particles, thereby biasing an otherwise random distribution to direct localized otolith seeding on tether cilia. Independent knockdown of subunits for the dynein regulatory complex and outer-arm dynein disrupt cilia motility, leading to defective otolith biogenesis. These results demonstrate a requirement for the dynein regulatory complex in vertebrates and show that cilia-driven flow is a key epigenetic factor in controlling otolith biomineralization.
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