Scaling of embryonic patterning based on phase-gradient encoding
Scaling of embryonic patterning based on phase-gradient encoding
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DOI：
10.1038/nature11804
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发表时间：
2013-01-03
期刊：
影响因子：
64.8
通讯作者：
Aulehla, Alexander
中科院分区：
文献类型：
--
作者：
Lauschke, Volker M.;Tsiairis, Charisios D.;Aulehla, Alexander
胚胎模式化的一个基本特征是尽管整体大小发生变化，但仍能够缩放并保持稳定的比例，例如在生长期间（1-6）。一个值得注意的例子发生在脊椎动物体节形成过程中：在胚胎大小实验性缩小后，体节形成比例更小，因此，正常数量的体节形成（1，7，8）。尽管经过了几十年的实验（1，7）和理论研究（9-11），其潜在机制仍然未知。最近，基因活动中的超日振荡与分割的时间控制有关（12）;然而，它们在缩放中的含义仍然难以捉摸。在这里，我们表明，缩放的基因振荡动力学的基础段缩放。为此，我们开发了一种新的实验模型，一种体外原代细胞培养试验，在准单层的前体中胚层细胞（以下称为单层PSM或mPSM）中重现小鼠中胚层图案化和节段缩放。结合基因活性的实时成像，这使我们能够量化振荡相位的逐渐变化，从而确定整个mPSM的相位梯度。至关重要的是，我们表明，这种相位梯度的尺度保持一个固定的振幅跨越不同长度的mPSM。我们确定了这个相位梯度的斜率作为一个单一的预测参数段的大小，其功能在一个大小和温度无关的方式，揭示了迄今未被认识到的缩放机制。值得注意的是，与分子梯度相反，相位梯度描述了动态细胞状态的分布。因此，我们的相位梯度缩放的发现揭示了一个新的水平的动态信息处理，并提供证据的概念相位梯度编码在胚胎图案和缩放。
A fundamental feature of embryonic patterning is the ability to scale and maintain stable proportions despite changes in overall size, for instance during growth(1-6). A notable example occurs during vertebrate segment formation: after experimental reduction of embryo size, segments form proportionally smaller, and consequently, a normal number of segments is formed(1,7,8). Despite decades of experimental(1,7) and theoretical work(9-11), the underlying mechanism remains unknown. More recently, ultradian oscillations in gene activity have been linked to the temporal control of segmentation(12); however, their implication in scaling remains elusive. Here we show that scaling of gene oscillation dynamics underlies segment scaling. To this end, we develop a new experimental model, an ex vivo primary cell culture assay that recapitulates mouse mesoderm patterning and segment scaling, in a quasi-monolayer of presomitic mesoderm cells (hereafter termed monolayer PSM or mPSM). Combined with real-time imaging of gene activity, this enabled us to quantify the gradual shift in the oscillation phase and thus determine the resulting phase gradient across the mPSM. Crucially, we show that this phase gradient scales by maintaining a fixed amplitude across mPSM of different lengths. We identify the slope of this phase gradient as a single predictive parameter for segment size, which functions in a size-and temperature-independent manner, revealing a hitherto unrecognized mechanism for scaling. Notably, in contrast to molecular gradients, a phase gradient describes the distribution of a dynamical cellular state. Thus, our phase-gradient scaling findings reveal a new level of dynamic information-processing, and provide evidence for the concept of phase-gradient encoding during embryonic patterning and scaling.