title: Cyclin O (Ccno) functions during deuterosome-mediated centriole amplification of multiciliated cells.
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.
authors.affiliation: University Medical Centre, Renal Department, Centre for Clinical Research, Freiburg, Germany Spemann Graduate School of Biology and Medicine, Freiburg, Germany.
authors.forename: Maja C
authors.initials: MC
authors.lastname: Funk
authors.affiliation: University Medical Centre, Renal Department, Centre for Clinical Research, Freiburg, Germany BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: Agata N
authors.initials: AN
authors.lastname: Bera
authors.affiliation: Department of Pediatrics, University Hospital Muenster, Muenster, Germany.
authors.forename: Tabea
authors.initials: T
authors.lastname: Menchen
authors.affiliation: University Medical Centre, Renal Department, Centre for Clinical Research, Freiburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Kuales
authors.affiliation: Department of Dermatology, ZBSA Centre for Biological Systems Analysis, Medical Centre University of Freiburg, Freiburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Thriene
authors.affiliation: University Medical Centre, Renal Department, Centre for Clinical Research, Freiburg, Germany BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: Soeren S
authors.initials: SS
authors.lastname: Lienkamp
authors.affiliation: BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University, Freiburg, Germany Department of Dermatology, ZBSA Centre for Biological Systems Analysis, Medical Centre University of Freiburg, Freiburg, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Dengjel
authors.affiliation: Department of Pediatrics, University Hospital Muenster, Muenster, Germany.
authors.forename: Heymut
authors.initials: H
authors.lastname: Omran
authors.affiliation: Medical Biology and Electron Microscopy Centre, University Medicine Rostock, Rostock, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Frank
authors.affiliation: University Medical Centre, Renal Department, Centre for Clinical Research, Freiburg, Germany BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University, Freiburg, Germany sebastian.arnold@uniklinik-freiburg.de.
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Arnold
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D002502:Centrioles / Q000502:physiology* / Q000648:ultrastructure; D002923:Cilia / Q000502:physiology / Q000648:ultrastructure; D016213:Cyclins / Q000502:physiology*; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D006849:Hydrocephalus / Q000196:embryology / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009079:Mucociliary Clearance / Q000235:genetics; D038081:Organogenesis / Q000235:genetics; D014132:Trachea / Q000166:cytology / Q000196:embryology / Q000378:metabolism
chemical_list: D016213:Cyclins; C539096:cyclin O, mouse
keywords: Ccno; centriole amplification; deuterosomes; mouse; multiciliated cells