Handling Editor: David Stephens
ABSTRACT
The molecular mechanisms by which cilia orientation is coordinated within and between multi-ciliated cells (MCCs) are not fully understood. In the mouse oviduct, MCCs exhibit a characteristic basal body (BB) orientation and microtubule gradient along the tissue axis. The intracellular polarities were moderately maintained in cells lacking CELSR1 (cadherin EGF LAG seven-pass G-type receptor 1), a planar cell polarity (PCP) factor involved in tissue polarity regulation, although the intercellular coordination of the polarities was disrupted. However, CAMSAP3 (calmodulin-regulated spectrin-associated protein 3), a microtubule minus-end regulator, was found to be critical for determining the intracellular BB orientation. CAMSAP3 localized to the base of cilia in a polarized manner, and its mutation led to the disruption of intracellular coordination of BB orientation, as well as the assembly of microtubules interconnecting BBs, without affecting PCP factor localization. Thus, both CELSR1 and CAMSAP3 are responsible for BB orientation but in distinct ways; their cooperation should therefore be critical for generating functional multi-ciliated tissues.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: F.M.U., M.A., T.F.; Methodology: F.M.U., M.A., D.S., T.F.; Software: M.A., D.S.; Investigation: F.M.U., D.S., Y.H.; Resources: S.O., Y.H., F.T., M.T.; Writing - original draft: F.M.U., M.A., M.T., T.F.; Writing - review & editing: F.M.U., M.A., T.F.; Visualization: F.M.U., M.A.; Supervision: M.T., T.F.; Project administration: T.F.; Funding acquisition: M.A., T.F.
Funding
This work was supported by the Japan Society for the Promotion of Science, KAKENHI (grant numbers 25291054, 15H01220, 17H03689, 16H06280 and 19K16153) and the Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (JPMJCR1654 to T.F.).
Supplementary information
Supplementary information available online at https://jcs.biologists.org/lookup/doi/10.1242/jcs.257006.supplemental
- Received November 7, 2020.
- Accepted January 4, 2021.
- © 2021. Published by The Company of Biologists Ltd
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