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Published January 8, 2009 | Accepted Version + Supplemental Material
Journal Article Open

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

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) 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.

Additional Information

© 2009 Nature Publishing Group. Received 16 July 2008; Accepted 30 September 2008; Published online 30 November 2008. We are grateful to R. Crosbie for discussions and encouragement throughout the course of the project. We thank I. Drummond and C. Nguyen for discussions and comments on the work. We are grateful to L. Trinh, O. Bricaud and A. Collazo for sharing reagents and for providing probes, as well as to all the members of the Fraser laboratory for discussions, in particular M. Liebling and W. Supatto for sharing Matlab scripts and comments. We are grateful to Z. P. Kabututu for performing the lrrc50 reverse transcriptase PCR experiments. J.V. was supported by a fellowship from the Human Frontier Science Program, D.W. was supported by the NIH Medical Scientist Training Program at UCLA/Caltech. J.R.C. was supported by NIH RSDA training grant no. M07185 and a Warsaw Fellowship from the MIMG Department at UCLA. A.D.L is supported by an NSF fellowship. This work was supported by NIH grant R01 HL081799 (J.C.), NIH grant R01AI52348 and Beckman Young Investigator Award (K.L.H.). Author Contributions: J.R.C., J.V., D.W. and K.L.H. designed the experiments and interpreted the results. J.R.C, J.V. and D.W. conducted the experiments. J.V. and D.W. developed the equipment and systems for and performed in vivo video imaging for the quantitative flow study and analyzed the data with J.R.C., S.F. and K.L.H. A.D.L. assisted with in situ hybridization. A.D.L. and J.C. provided guidance on gas8 morpholino injections. The manuscript was written by J.R.C., J.V., D.W. and K.L.H. All authors discussed the results and commented on the manuscript.

Attached Files

Accepted Version - nihms152359.pdf

Supplemental Material - nature07520-s1.pdf

Supplemental Material - nature07520-s10.mov

Supplemental Material - nature07520-s11.mov

Supplemental Material - nature07520-s12.mov

Supplemental Material - nature07520-s13.mov

Supplemental Material - nature07520-s14.mov

Supplemental Material - nature07520-s15.mov

Supplemental Material - nature07520-s2.mov

Supplemental Material - nature07520-s3.mov

Supplemental Material - nature07520-s4.mov

Supplemental Material - nature07520-s5.mov

Supplemental Material - nature07520-s6.mov

Supplemental Material - nature07520-s7.mov

Supplemental Material - nature07520-s8.mov

Supplemental Material - nature07520-s9.mov

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Additional details

Created:
August 22, 2023
Modified:
October 17, 2023