RFX3 governs growth and beating efficiency of motile cilia in mouse and controls the expression of genes involved in human ciliopathies
RFX3 governs growth and beating efficiency of motile cilia in mouse and controls the expression of genes involved in human ciliopathies
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DOI：
10.1242/jcs.048348
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发表时间：
2009-09-01
影响因子：
4
通讯作者：
Durand, Benedicte
中科院分区：
文献类型：
--
作者：
El Zein, Loubna;Ait-Lounis, Aouatef;Durand, Benedicte
纤毛是一种细胞器，在各种生物体中发挥着重要的生理和发育功能。根据纤毛轴丝结构的不同，纤毛可分为初级纤毛和运动纤毛两大类。调节因子X（RFX）转录因子已被证明参与秀丽隐杆线虫、果蝇和小鼠初级纤毛的组装。在这里，我们已经利用了一种新的原代细胞培养系统，从小鼠大脑显示RFX 3也是必要的运动纤毛的生物合成。我们发现在多纤毛的Rfx 3（-/-）细胞中运动纤毛的生长和搏动效率受损。RFX 3是FOXJ 1转录因子最佳表达所需的，FOXJ 1转录因子是活动纤毛分化程序中的关键因素。此外，我们首次证明RFX 3通过直接与其基因的启动子结合来调节参与纤毛运动的轴丝动力蛋白的表达。总之，RFX蛋白不仅调节参与纤毛组装的基因，而且还调节参与纤毛运动和与纤毛病如人类原发性纤毛运动障碍相关的基因。
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.