Mutations in CCNO and MCIDAS lead to a mucociliary clearance disorder due to reduced generation of multiple motile cilia

نویسندگان

  • J Wallmeier
  • M Boon
  • D Al Mutairi
  • NT Loges
  • L Ma
  • C-T Chen
  • H Olbrich
  • P Pennekamp
  • T Menchen
  • G Dougherty
  • C Werner
  • M Jaspers
  • M Griese
  • E Horak
  • C Körner-Rettberg
  • S Schmitt-Grohé
  • T Zimmermann
  • A Hevroni
  • R Abitbul
  • A Avital
  • R Soferman
  • I Amirav
  • H Mitchison
  • M Jorissen
  • F Alkuraya
  • C Kintner
  • H Omran
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Cyclin O (Ccno) functions during deuterosome-mediated centriole amplification of multiciliated cells.

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 i...

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GemC1 controls multiciliogenesis in the airway epithelium.

Multiciliated cells are terminally differentiated, post-mitotic cells that form hundreds of motile cilia on their apical surface. Defects in multiciliated cells lead to disease, including mucociliary clearance disorders that result from ciliated cell disfunction in airways. The pathway controlling multiciliogenesis, however, remains poorly characterized. We showed that GemC1, previously implica...

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Constitutive Cyclin O deficiency results in penetrant hydrocephalus, impaired growth and infertility

Cyclin O (encoded by CCNO) is a member of the cyclin family with regulatory functions in ciliogenesis and apoptosis. Homozygous CCNO mutations have been identified in human patients with Reduced Generation of Multiple Motile Cilia (RGMC) and conditional inactivation of Ccno in the mouse recapitulates some of the pathologies associated with the human disease. These include defects in the develop...

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Mucociliary Transport in Healthy and Diseased Environments

Mucociliary clearance in the lung is the primary defense mechanism that protects the airways from inhaled toxicants and infectious agents. The system consists of a viscoelastic mucus layer on top of a nearly-viscous periciliary layer surrounding the motile cilia. In healthy environments, the thickness of the periciliary layer is comparable to the cilia length. Perturbations to this system, whet...

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Dev126342 3661..3674

Multiciliated cells are abundant in the epithelial surface of different tissues, including cells lining thewalls of the lateral ventricles in the brain and the airway epithelium. Their main role is to control fluid flow and defects in their differentiation are implicated in many human disorders, such as hydrocephalus, accompanied by defects in adult neurogenesis and mucociliary disorder in the ...

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عنوان ژورنال:

دوره 2  شماره 

صفحات  -

تاریخ انتشار 2015