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首页> 外文期刊>Cell cycle >MicroRNA-based silencing of Delta/Notch signaling promotes multiple cilia formation.
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MicroRNA-based silencing of Delta/Notch signaling promotes multiple cilia formation.

机译:基于Delta / Notch信号的基于MicroRNA的沉默可促进多个纤毛形成。

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摘要

Multiciliated cells lining the surface of some vertebrate epithelia are essential for various physiological processes, such as airway cleansing. Their apical surface is constituted by hundreds of motile cilia, which beat in a coordinated manner to generate directional fluid flow. We recently reported the identification of microRNAs of the miR-449 family as evolutionary conserved key regulators of vertebrate multiciliogenesis. This novel function of miR-449 was established using in vivo and in vitro antisense approaches in two distinct experimental models. miR-449 strongly accumulated in multiciliated cells in human airway epithelium and Xenopus laevis embryonic epidermis, where it triggered centriole multiplication and multiciliogenesis by directly repressing the Delta/Notch pathway. Our data complement previous reports that showed the blocking action of miR-449 on the cell cycle, and unraveled a novel conserved mechanism whereby Notch signaling must undergo microRNA-mediated inhibition to permit differentiation of ciliated cell progenitors. We review here several important questions regarding the links between microRNAs and the Notch pathway in the control of cell fate.
机译:某些脊椎动物上皮细胞表面的多纤毛细胞对于各种生理过程(如气道清洁)至关重要。它们的顶端表面由数百个活动纤毛构成,这些纤毛以协调的方式跳动以产生定向的流体流。我们最近报道了鉴定miR-449家族的microRNA作为脊椎动物多纤毛发生的进化保守关键调节因子。使用体内和体外反义方法在两个不同的实验模型中建立了miR-449的这一新功能。 miR-449在人气道上皮细胞和非洲爪蟾胚胎表皮中的多纤毛细胞中强烈积累,并通过直接抑制Delta / Notch途径触发了中心体增殖和多纤毛发生。我们的数据补充了先前的报道,这些报道显示了miR-449在细胞周期中的阻断作用,并揭示了一种新颖的保守机制,其中Notch信号传导必须经过microRNA介导的抑制作用才能允许纤毛细胞祖细胞分化。我们在这里复习一些有关microRNA与Notch通路在细胞命运控制中的联系的重要问题。

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