Developmental Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany, European Molecular Biology Laboratory, 69117 Heidelberg, Germany; Genome Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Developmental Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Cell. 2018 Feb 22;172(5):1079-1090.e12. doi: 10.1016/j.cell.2018.01.026.
How signaling dynamics encode information is a central question in biology. During vertebrate development, dynamic Notch signaling oscillations control segmentation of the presomitic mesoderm (PSM). In mouse embryos, this molecular clock comprises signaling oscillations of several pathways, i.e., Notch, Wnt, and FGF signaling. Here, we directly address the role of the relative timing between Wnt and Notch signaling oscillations during PSM patterning. To this end, we developed a new experimental strategy using microfluidics-based entrainment that enables specific control of the rhythm of segmentation clock oscillations. Using this approach, we find that Wnt and Notch signaling are coupled at the level of their oscillation dynamics. Furthermore, we provide functional evidence that the oscillation phase shift between Wnt and Notch signaling is critical for PSM segmentation. Our work hence reveals that dynamic signaling, i.e., the relative timing between oscillatory signals, encodes essential information during multicellular development.
信号动态如何编码信息是生物学中的一个核心问题。在脊椎动物发育过程中，动态 Notch 信号振荡控制着体节中胚层 (PSM) 的分割。在小鼠胚胎中，这个分子钟由几个途径的信号振荡组成，即 Notch、Wnt 和 FGF 信号。在这里，我们直接研究了 Wnt 和 Notch 信号振荡在 PSM 模式形成过程中的相对时间的作用。为此，我们开发了一种新的实验策略，使用基于微流控的同步，能够特异性地控制分段时钟振荡的节律。使用这种方法，我们发现 Wnt 和 Notch 信号在其振荡动力学水平上是耦合的。此外，我们提供了功能证据表明，Wnt 和 Notch 信号之间的振荡相位差对于 PSM 分割是至关重要的。因此，我们的工作揭示了动态信号，即振荡信号之间的相对时间，在细胞发育过程中编码了重要信息。
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