@article{23984751738649278457a6a55345b90c,
title = "Massive centriole production can occur in the absence of deuterosomes in multiciliated cells",
abstract = "Multiciliated cells (MCCs) amplify large numbers of centrioles that convert into basal bodies, which are required for producing multiple motile cilia. Most centrioles amplified by MCCs grow on the surface of organelles called deuterosomes, whereas a smaller number grow through the centriolar pathway in association with the two parent centrioles. Here, we show that MCCs lacking deuterosomes amplify the correct number of centrioles with normal step-wise kinetics. This is achieved through a massive production of centrioles on the surface and in the vicinity of parent centrioles. Therefore, deuterosomes may have evolved to relieve, rather than supplement, the centriolar pathway during multiciliogenesis. Remarkably, MCCs lacking parent centrioles and deuterosomes also amplify the appropriate number of centrioles inside a cloud of pericentriolar and fibrogranular material. These data show that the centriole number is set independently of their nucleation platforms and suggest that massive centriole production in MCCs is a robust process that can self-organize.",
author = "Olivier Mercey and Levine, {Michelle S.} and LoMastro, {Gina M.} and Philippe Rostaing and Eva Brotslaw and Valerie Gomez and Abhijay Kumar and Nathalie Spassky and Mitchell, {Brian J.} and Alice Meunier and Holland, {Andrew J.}",
note = "Funding Information: Deup1−/− mice. Deup1 heterozygous sperm (Deup1tm1.1(KOMP)Vlcg) was obtained from the U.C.-Davis Knockout Mouse Phenotyping Consortium (project ID: VG11314). NIH grants to Velocigene at Regeneron Inc (U01HG004085) and the CSD Consortium (U01HG004080) funded the generation of gene-targeted ES cells for 8,500 genes in the KOMP Program and archived and distributed by the KOMP Repository at UC Davis and CHORI (U42RR024244). The mice were rederived at the Transgenic Core Laboratory, Johns Hopkins University School of Medicine, using C57B/L6N mice. These animals were maintained on a congenic C57BL/6N background. The following primers pairs were used for genotyping: Mut For, 5′-acttgctttaaaaaacctcccaca-3′ and Mut Rev, 5′-ggaagtagactaacgtggagcaagc-3′; WT For, 5′-tagggcactgttgggtatattgg-3′ and WT Rev, 5′-ccacacatttctgcttctcc-3′. Embryos and adults from both genders were included in our analysis. Funding Information: We thank all of the members of the Spassky laboratory for their comments and discussions, M. Legendre for identifying the DEUP1 mutation on the gnomAD control database, K. Oegema and A.K. Shiau (Ludwig Institute for Cancer Research) for sharing centrinone, A.-K. Konate and R. Nagalingum for administrative support and the IBENS Animal Facility for animal care. We thank the IBENS Imaging Facility, with grants from R{\'e}gion Ile-de-France (NERF 2011-45), Fondation pour la Recherche M{\'e}dicale (FRM; DGE 20111123023), and F{\'e}d{\'e}ration pour la Recherche sur le Cerveau– Rotary International France (2011). We thank Y. Wang of the Nathans laboratory for technical assistance. The authors would like to thank the Genome Aggregation Database (gnomAD) and the groups that provided the exome and genome variant data to this resource. We are grateful to J. Nathans, A. Rosen and the Johns Hopkins Institute for Basic Biomedical Sciences for providing research support to A.J.H. This work was supported by grants from the National Institutes of Health (R01GM114119 and R01GM133897) and an American Cancer Society Scholar (RSG-16-156-01-CCG) to A.J.H., National Institutes of Health (R01GM089970) to B.M., Agence Nationale de la Recherche (ANR) Investissements d{\textquoteright}Avenir (ANR-10-LABX-54 MEMO LIFE and ANR-11-IDEX-0001-02 PSL Research University) to IBENS. The Spassky laboratory is supported by INSERM, CNRS, EcoleNormale Sup{\'e}rieure (ENS), FRM (EquipeFRM grant 20140329547), a European Research Council (ERC Consolidator grant 647466) to N.S. and ANR (ANRJC JC-15-CE13-0005-01) to A.M. Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41556-019-0427-x",
language = "English (US)",
volume = "21",
pages = "1544--1552",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "12",
}