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First published online 11 August 2009
doi: 10.1242/jcs.048348

Journal of Cell Science 122, 3180-3189 (2009)
Published by The Company of Biologists 2009
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Research Article

RFX3 governs growth and beating efficiency of motile cilia in mouse and controls the expression of genes involved in human ciliopathies

Loubna El Zein1, Aouatef Ait-Lounis2, Laurette Morlé1, Joëlle Thomas1, Brigitte Chhin1, Nathalie Spassky3, Walter Reith2 and Bénédicte Durand1,*

1 Université de Lyon, Lyon, F-69003, Université Lyon 1, CNRS, UMR5534, CGMC, Centre de Génétique Moléculaire et Cellulaire, Villeurbanne, F-69622, France
2 Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, CMU, 1 rue Michel-Servet, CH-1211 Geneva, Switzerland
3 INSERM U711, Hôpital Salpêtrière, 47 Boulevard de l'hôpital, 75013 Paris, France

* Author for correspondence (durand-b{at}univ-lyon1.fr)

Accepted 21 June 2009

Cilia are cellular organelles that play essential physiological and developmental functions in various organisms. They can be classified into two categories, primary cilia and motile cilia, on the basis of their axonemal architecture. Regulatory factor X (RFX) transcription factors have been shown to be involved in the assembly of primary cilia in Caenorhabditis elegans, Drosophila and mice. Here, we have taken advantage of a novel primary-cell culture system derived from mouse brain to show that RFX3 is also necessary for biogenesis of motile cilia. We found that the growth and beating efficiencies of motile cilia are impaired in multiciliated Rfx3–/– cells. RFX3 was required for optimal expression of the FOXJ1 transcription factor, a key player in the differentiation program of motile cilia. Furthermore, we demonstrate for the first time that RFX3 regulates the expression of axonemal dyneins involved in ciliary motility by binding directly to the promoters of their genes. In conclusion, RFX proteins not only regulate genes involved in ciliary assembly, but also genes that are involved in ciliary motility and that are associated with ciliopathies such as primary ciliary dyskinesia in humans.

Key words: Axonemal dyneins, Cilia, Mouse primary cell cultures, Primary ciliary dyskinesia, RFX proteins


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Related articles in JCS:

RFX3: the X factor for motile cilia

JCS 2009 122: 1702. [Full Text]  





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