Regulation of cilia abundance in multiciliated cells

  1. Rashmi Nanjundappa
  2. Dong Kong
  3. Kyuhwan Shim
  4. Tim Stearns
  5. Steven L Brody
  6. Jadranka Loncarek
  7. Moe R Mahjoub  Is a corresponding author
  1. Washington University in St Louis, United States
  2. National Cancer Institute, National Institutes of Health, United States
  3. 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

  1. Rashmi Nanjundappa

    Department of Medicine (Nephrology Division), Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3621-4628
  2. Dong Kong

    Laboratory of Protein Dynamics and Signaling, Center for Cancer Research - Frederick, National Cancer Institute, National Institutes of Health, Frederick, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kyuhwan Shim

    Department of Medicine (Nephrology Division), Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Tim Stearns

    Department of Biology, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0671-6582
  5. Steven L Brody

    Department of Medicine (Pulmonary Division), Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jadranka Loncarek

    Laboratory of Protein Dynamics and Signaling, Center for Cancer Research - Frederick, National Cancer Institute, National Institutes of Health, Frederick, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Moe R Mahjoub

    Department of Medicine (Nephrology Division), Washington University in St Louis, St Louis, United States
    For correspondence
    mmahjoub@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8129-7464

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.

Reviewing Editor

  1. Jeremy F Reiter, University of California, San Francisco, United States

Version history

  1. Received: November 30, 2018
  2. Accepted: April 25, 2019
  3. Accepted Manuscript published: April 26, 2019 (version 1)
  4. Version of Record published: May 7, 2019 (version 2)

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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  1. Rashmi Nanjundappa
  2. Dong Kong
  3. Kyuhwan Shim
  4. Tim Stearns
  5. Steven L Brody
  6. Jadranka Loncarek
  7. Moe R Mahjoub
(2019)
Regulation of cilia abundance in multiciliated cells
eLife 8:e44039.
https://doi.org/10.7554/eLife.44039

Share this article

https://doi.org/10.7554/eLife.44039

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