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Microtubule-dependent orchestration of centriole amplification in brain multiciliated cells

Amélie-Rose Boudjema, Rémi Balagué, View ORCID ProfileCayla E Jewett, Gina M LoMastro, Olivier Mercey, Adel Al Jord, Marion Faucourt, Alexandre Schaeffer, Camille Noûs, View ORCID ProfileNathalie Delgehyr, View ORCID ProfileAndrew J Holland, Nathalie Spassky, Alice Meunier
doi: https://doi.org/10.1101/2024.02.09.579615
Amélie-Rose Boudjema
1Institut de Biologie de l’École Normale Supérieure (IBENS), Paris Sciences et Lettres (PSL). Research University, Paris, F-75005, France. CNRS, UMR 8197, Paris, F-75005, France. INSERM, U1024, Paris, F-75005, France
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Rémi Balagué
1Institut de Biologie de l’École Normale Supérieure (IBENS), Paris Sciences et Lettres (PSL). Research University, Paris, F-75005, France. CNRS, UMR 8197, Paris, F-75005, France. INSERM, U1024, Paris, F-75005, France
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Cayla E Jewett
2Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States
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  • ORCID record for Cayla E Jewett
Gina M LoMastro
2Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States
3Seagen Inc., Bothell, Washington, United States
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Olivier Mercey
4Department of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland
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Adel Al Jord
5Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain
6Universitat Pompeu Fabra (UPF), Barcelona, Spain
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Marion Faucourt
1Institut de Biologie de l’École Normale Supérieure (IBENS), Paris Sciences et Lettres (PSL). Research University, Paris, F-75005, France. CNRS, UMR 8197, Paris, F-75005, France. INSERM, U1024, Paris, F-75005, France
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Alexandre Schaeffer
7CytoMorpho Lab, Laboratoire de Physiologie Cellulaire & Végétale, Interdisciplinary Research Institute of Grenoble, University of Grenoble-Alpes, CEA, CNRS, INRA, Grenoble, France
8CytoMorpho Lab, UMR8231, ESPCI, University PSL, CEA, Paris, France
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Camille Noûs
9Cogitamus Laboratory, PSL University
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Nathalie Delgehyr
1Institut de Biologie de l’École Normale Supérieure (IBENS), Paris Sciences et Lettres (PSL). Research University, Paris, F-75005, France. CNRS, UMR 8197, Paris, F-75005, France. INSERM, U1024, Paris, F-75005, France
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  • ORCID record for Nathalie Delgehyr
Andrew J Holland
2Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States
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Nathalie Spassky
1Institut de Biologie de l’École Normale Supérieure (IBENS), Paris Sciences et Lettres (PSL). Research University, Paris, F-75005, France. CNRS, UMR 8197, Paris, F-75005, France. INSERM, U1024, Paris, F-75005, France
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Alice Meunier
1Institut de Biologie de l’École Normale Supérieure (IBENS), Paris Sciences et Lettres (PSL). Research University, Paris, F-75005, France. CNRS, UMR 8197, Paris, F-75005, France. INSERM, U1024, Paris, F-75005, France
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  • For correspondence: [email protected]
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Abstract

Centriole number must be restricted to two in cycling cells to avoid pathological cell divisions. Multiciliated cells (MCC), however, need to produce a hundred or more centrioles to nucleate the same number of motile cilia required for fluid flow circulation. These centrioles are produced by highjacking cell cycle and centriole duplication programs. However, how the MCC progenitor handles such a massive number of centrioles to finally organize them in an apical basal body patch is unclear. Here, using new cellular models and high-resolution imaging techniques, we identify the microtubule network as the bandleader, and show how it orchestrates the process in space and in time. Organized by the pre-existing centrosome at the start of amplification, microtubules build a nest of centriolar components from which procentrioles emerge. When amplification is over, the centrosome’s dominance is lost as new centrioles mature and become microtubule nucleators. Microtubules then drag all the centrioles to the nuclear membrane, assist their isotropic perinuclear disengagement and their subsequent collective apical migration. These results reveal that in brain MCC as in cycling cells, the same dynamics - from the centrosome to the cell pole via the nucleus-exists, is the result of a reflexive link between microtubules and the progressive maturation of new centrioles, and participates in the organized reshaping of the entire cytoplasm. On the other hand, new elements described in this work such as microtubule-driven organization of a nest, identification of a spatio-temporal progression of centriole growth and microtubule-assisted disengagement, may shed new light on the centriole duplication program.

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Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted February 12, 2024.
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Microtubule-dependent orchestration of centriole amplification in brain multiciliated cells
Amélie-Rose Boudjema, Rémi Balagué, Cayla E Jewett, Gina M LoMastro, Olivier Mercey, Adel Al Jord, Marion Faucourt, Alexandre Schaeffer, Camille Noûs, Nathalie Delgehyr, Andrew J Holland, Nathalie Spassky, Alice Meunier
bioRxiv 2024.02.09.579615; doi: https://doi.org/10.1101/2024.02.09.579615
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Microtubule-dependent orchestration of centriole amplification in brain multiciliated cells
Amélie-Rose Boudjema, Rémi Balagué, Cayla E Jewett, Gina M LoMastro, Olivier Mercey, Adel Al Jord, Marion Faucourt, Alexandre Schaeffer, Camille Noûs, Nathalie Delgehyr, Andrew J Holland, Nathalie Spassky, Alice Meunier
bioRxiv 2024.02.09.579615; doi: https://doi.org/10.1101/2024.02.09.579615

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