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

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 t...

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Published inJournal of cell science Vol. 122; no. 17; pp. 3180 - 3189
Main Authors El Zein, Loubna, Ait-Lounis, Aouatef, Morlé, Laurette, Thomas, Joëlle, Chhin, Brigitte, Spassky, Nathalie, Reith, Walter, Durand, Bénédicte
Format Journal Article
LanguageEnglish
Published England The Company of Biologists Limited 01.09.2009
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Abstract 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.
AbstractList 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.
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.
Author Thomas, Joëlle
Durand, Bénédicte
Reith, Walter
Chhin, Brigitte
Spassky, Nathalie
El Zein, Loubna
Morlé, Laurette
Ait-Lounis, Aouatef
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Snippet Cilia are cellular organelles that play essential physiological and developmental functions in various organisms. They can be classified into two categories,...
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SubjectTerms Amino Acid Sequence
Animals
Biochemistry, Molecular Biology
Cilia - chemistry
Cilia - physiology
Ciliary Motility Disorders - genetics
Ciliary Motility Disorders - metabolism
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Gene Expression Regulation, Developmental
Humans
Life Sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular biology
Molecular Sequence Data
Protein Binding
Regulatory Factor X Transcription Factors
Sequence Alignment
Transcription Factors - chemistry
Transcription Factors - genetics
Transcription Factors - metabolism
Title RFX3 governs growth and beating efficiency of motile cilia in mouse and controls the expression of genes involved in human ciliopathies
URI https://www.ncbi.nlm.nih.gov/pubmed/19671664
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https://hal.science/hal-00425116
Volume 122
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