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首页> 外文期刊>Nature cell biology >Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation.
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Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation.

机译：Multicilin促进多纤毛细胞分化过程中的中心体组装和纤毛发生。

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摘要

Multiciliate cells function prominently in the respiratory system, brain ependyma and female reproductive tract to produce vigorous fluid flow along epithelial surfaces. These specialized cells form during development when epithelial progenitors undergo an unusual form of ciliogenesis, in which they assemble and project hundreds of motile cilia. Notch inhibits multiciliate cell formation in diverse epithelia, but how progenitors overcome lateral inhibition and initiate multiciliate cell differentiation is unknown. Here we identify a coiled-coil protein, termed multicilin, which is regulated by Notch and highly expressed in developing epithelia where multiciliate cells form. Inhibiting multicilin function specifically blocks multiciliate cell formation in Xenopus skin and kidney, whereas ectopic expression induces the differentiation of multiciliate cells in ectopic locations. Multicilin localizes to the nucleus, where it directly activates the expression of genes required for multiciliate cell formation, including foxj1 and genes mediating centriole assembly. Multicilin is also necessary and sufficient to promote multiciliate cell differentiation in mouse airway epithelial cultures. These findings indicate that multicilin initiates multiciliate cell differentiation in diverse tissues, by coordinately promoting the transcriptional changes required for motile ciliogenesis and centriole assembly.
机译：多纤毛细胞在呼吸系统，脑室管膜增生和女性生殖道中发挥重要作用，从而沿着上皮表面产生旺盛的液体流动。当上皮祖细胞经历异常的纤毛发生形式时，这些专门的细胞在发育过程中形成，它们在其中组装并投射成百上千的活动纤毛。 Notch可抑制多种上皮细胞的多纤毛细胞形成，但是祖细胞如何克服侧向抑制并启动多纤毛细胞分化尚不清楚。在这里，我们确定了被称为多丝菌素的卷曲螺旋蛋白，该蛋白受Notch调控，并在形成多纤毛细胞的发育中的上皮中高度表达。抑制multicilin功能可特异性阻断非洲爪蟾皮肤和肾脏中多纤毛细胞的形成，而异位表达可诱导异位部位多纤毛细胞的分化。 Multicilin定位于细胞核，直接激活多纤毛细胞形成所需基因的表达，包括foxj1和介导中心细胞装配的基因。在小鼠气道上皮培养物中，Multicilin也是促进多纤毛细胞分化的必要和充分条件。这些发现表明，multicilin通过协调促进活动性纤毛发生和中心粒组装所需的转录变化，在多种组织中启动了纤毛细胞分化。

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