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The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear
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The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear
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Journal Article
The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear
2009
Overview
Cilia strike a balance
In zebrafish — as in humans and other vertebrates — hearing and balance are mediated by mechanical sensors in the inner ear. These sensors consist of biomineralized composite crystals, called otoliths. Colantonio
et al
. use
in vivo
video microscopy of zebrafish embryos to show that fluid flow generated by cilia influences the number, growth and localization of otoliths, as well as their mineralization during development. Gene-knockdown with 'morpholino' antisense oligonucleotides shows that the dynein regulatory complex is required for cilium motility. Thus cilia-driven flow appears to be a key epigenetic factor in controlling otolith biomineralization, and dynein regulatory complex subunits emerge as candidates for disease genes for ciliopathies in humans.
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', orotoliths. This paper show that in zebra fish, fluid flow generated by cilia influences the number, growth and localization of otoliths, as well as their mineralization during development.
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)
1
. 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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Biochemistry, Molecular Biology
/ Biological and medical sciences
/ Embryos
/ Fundamental and applied biological sciences. Psychology
/ Humanities and Social Sciences
/ Humans
/ letter
/ Life
/ Microtubule Proteins - chemistry
/ Microtubule Proteins - deficiency
/ Microtubule Proteins - genetics
/ Microtubule Proteins - metabolism
/ Movement
/ Multiprotein Complexes - deficiency
/ Multiprotein Complexes - genetics
/ Multiprotein Complexes - metabolism
/ Origin
/ Otolithic Membrane - cytology
/ Otolithic Membrane - embryology
/ Otolithic Membrane - metabolism
/ Otoliths
/ Science
/ Sensors
/ Vertebrates: nervous system and sense organs
/ Zebrafish Proteins - chemistry
/ Zebrafish Proteins - deficiency
