Cyclin O (Ccno) functions during deuterosome-mediated centriole amplification of multiciliated cells |
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| Authors: | Maja C Funk Agata N Bera Tabea Menchen Georg Kuales Kerstin Thriene Soeren S Lienkamp Jörn Dengjel Heymut Omran Marcus Frank Sebastian J Arnold |
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| Affiliation: | 1. University Medical Centre, Renal Department, Centre for Clinical Research, Freiburg, Germany;2. Spemann Graduate School of Biology and Medicine, Freiburg, Germany;3. BIOSS Centre of Biological Signalling Studies, Albert‐Ludwigs‐University, Freiburg, Germany;4. Department of Pediatrics, University Hospital Muenster, Muenster, Germany;5. Department of Dermatology, ZBSA Centre for Biological Systems Analysis, Medical Centre, University of Freiburg, Freiburg, Germany;6. Medical Biology and Electron Microscopy Centre, University Medicine Rostock, Rostock, Germany |
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| Abstract: | Mucociliary clearance and fluid transport along epithelial surfaces are carried out by multiciliated cells (MCCs). Recently, human mutations in Cyclin O (CCNO) were linked to severe airway disease. Here, we show that Ccno expression is restricted to MCCs and the genetic deletion of Ccno in mouse leads to reduced numbers of multiple motile cilia and characteristic phenotypes of MCC dysfunction including severe hydrocephalus and mucociliary clearance deficits. Reduced cilia numbers are caused by compromised generation of centrioles at deuterosomes, which serve as major amplification platform for centrioles in MCCs. Ccno-deficient MCCs fail to sufficiently generate deuterosomes, and only reduced numbers of fully functional centrioles that undergo maturation to ciliary basal bodies are formed. Collectively, this study implicates CCNO as first known regulator of deuterosome formation and function for the amplification of centrioles in MCCs. |
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| Keywords: | Ccno centriole amplification deuterosomes mouse multiciliated cells |
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