Regulation of cilia abundance in multiciliated cells
- Washington University in St Louis, United States
- National Cancer Institute, National Institutes of Health, United States
- Stanford University, United States
Abstract
Multiciliated cells (MCC) contain hundreds of motile cilia used to propel fluid over their surface. To template these cilia, each MCC produces between 100-600 centrioles by a process termed centriole amplification. Yet, how MCC regulate the precise number of centrioles and cilia remains unknown. Airway progenitor cells contain two parental centrioles (PC) and form structures called deuterosomes that nucleate centrioles during amplification. Using an ex vivo airway culture model, we show that ablation of PC does not perturb deuterosome formation and centriole amplification. In contrast, loss of PC caused an increase in deuterosome and centriole abundance, highlighting the presence of a compensatory mechanism. Quantification of centriole abundance in vitro and in vivo identified a linear relationship between surface area and centriole number. By manipulating cell size, we discovered that centriole number scales with surface area. Our results demonstrate that a cell-intrinsic surface area-dependent mechanism controls centriole and cilia abundance in multiciliated cells.
Data availability
All data generated or analysed during this study are included in the manuscript
Article and author information
Author details
Rashmi Nanjundappa
Funding
National Heart, Lung, and Blood Institute (R01-HL128370)
- Steven L Brody
- Moe R Mahjoub
National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK108005)
- Moe R Mahjoub
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Moreover, the experiments were performed following approved protocols that are compliant with guidelines of the Institutional Animal Care and Use Committee at Washington University (approval # 20180237) . Mice were euthanized using carbon dioxide inhalation followed by cervical dislocation, and every effort was made to minimize suffering and distress.
Copyright
© 2019, Nanjundappa et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Regulation of cilia abundance in multiciliated cells
eLife 8:e44039.
https://doi.org/10.7554/eLife.44039
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