论文标题
通过细胞 - 细胞信号传导形态梯度中的强大边界形成
Robust boundary formation in a morphogen gradient via cell-cell signaling
论文作者
论文摘要
在空间基因表达模式中建立尖锐并正确定位的边界是发育和合成生物学的核心任务。我们考虑了全局形态梯度为细胞提供位置信息的情况,但由于系统中不同类型的噪声,不足以确保所需的边界精度。在概念模型中,我们定量比较了三种机制,这些机制将全局信号与相邻单元之间的局部信号结合在一起,以增强边界形成过程。这些机制在遵循AN和AN或A和总和规则的情况下组合信号的方式方面有所不同。在我们的模型中,我们分析边界形成过程的动力学以及所得边界的模糊性。此外,我们考虑边界位置的可调节性及其随系统大小的缩放。我们认为,这三种机制的模糊边界比纯粹基于梯度的参考机制少,即使在局部信号中相对于全局信号中的噪声的高噪声状态也是如此。在这三种机制中,总和规则产生最准确的边界。但是,与其他两种机制相反,它需要噪声才能退出亚稳态并迅速达到稳定的边界模式。
Establishing sharp and correctly positioned boundaries in spatial gene expression patterns is a central task, both in developmental and synthetic biology. We consider situations where a global morphogen gradient provides positional information to cells, but is insufficient to ensure the required boundary precision, due to different types of noise in the system. In a conceptual model, we quantitatively compare three mechanisms, which combine the global signal with local signaling between neighboring cells, to enhance the boundary formation process. These mechanisms differ with respect to the way in which they combine the signals, by following either an AND, an OR, or a SUM rule. Within our model, we analyze the dynamics of the boundary formation process, and the fuzziness of the resulting boundary. Furthermore, we consider the tunability of the boundary position, and its scaling with system size. We nd that all three mechanisms produce less fuzzy boundaries than the purely gradient-based reference mechanism, even in the regime of high noise in the local signals relative to the noise in the global signal. Among the three mechanisms, the SUM rule produces the most accurate boundary. However, in contrast to the other two mechanisms, it requires noise to exit metastable states and rapidly reach the stable boundary pattern.