Lfng regulates the synchronized oscillation of the mouse segmentation clock via trans-repression of Notch signalling
Lfng regulates the synchronized oscillation of the mouse segmentation clock via trans-repression of Notch signalling
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DOI：
10.1038/ncomms2133
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发表时间：
2012-10-01
影响因子：
16.6
通讯作者：
Saga, Yumiko
中科院分区：
文献类型：
--
作者：
Okubo, Yusuke;Sugawara, Takeshi;Saga, Yumiko
在体节发生过程中，需要体节时钟的同步振荡来产生清晰的体节边界。然而，小鼠胚胎中这种同步化的分子机制尚未阐明。我们使用实验和理论方法来解决这个关键问题。在这里，我们表明，使用嵌合胚胎组成的野生型细胞和三角洲样1（Dll 1）-空细胞，Dll 1介导的Notch信号是负责的同步机制。通过分析Lunatic fringe（Lfng）嵌合胚胎和使用共培养系统的Notch信号报告基因测定，我们进一步发现Lfng通过调节Dll 1功能来抑制邻近细胞中的Notch活性。最后，数值模拟证实Lfng对邻近细胞中Notch活性的抑制作用可以充分解释体内同步化。总的来说，我们提供了一个新的模型，其中Lfng通过反式抑制机制在细胞间的耦合中起着至关重要的作用。
The synchronized oscillation of segmentation clock is required to generate a sharp somite boundary during somitogenesis. However, the molecular mechanism underlying this synchronization in the mouse embryos is not clarified yet. We used both experimental and theoretical approaches to address this key question. Here we show, using chimeric embryos composed of wild-type cells and Delta like 1 (Dll1)-null cells, that Dll1-mediated Notch signalling is responsible for the synchronization mechanism. By analysing Lunatic fringe (Lfng) chimeric embryos and Notch signal reporter assays using a co-culture system, we further find that Lfng represses Notch activity in neighbouring cells by modulating Dll1 function. Finally, numerical simulations confirm that the repressive effect of Lfng against Notch activities in neighbouring cells can sufficiently explain the synchronization in vivo. Collectively, we provide a new model in which Lfng has a crucial role in intercellular coupling of the segmentation clock through a trans-repression mechanism.