Regulation of cilia abundance in multiciliated cells

Author:

Nanjundappa Rashmi1ORCID,Kong Dong2,Shim Kyuhwan1,Stearns Tim3ORCID,Brody Steven L4,Loncarek Jadranka2,Mahjoub Moe R15ORCID

Affiliation:

1. Nephrology Division, Department of Medicine, Washington University, St Louis, United States

2. Center for Cancer Research, National Cancer Institute, Frederick, United States

3. Department of Biology, Stanford University, Stanford, United States

4. Pulmonary Division, Department of Medicine, Washington University, St Louis, United States

5. Department of Cell Biology and Physiology, Washington University, St Louis, 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.

Funder

National Heart, Lung, and Blood Institute

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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