超越法国国旗模型：利用空间和基因调节相互作用获取位置信息
Beyond the French Flag Model: Exploiting Spatial and Gene Regulatory Interactions for Positional Information
摘要：
多细胞生物体早期发育的关键步骤包括建立基因表达的空间模式，该空间模式随后指导增殖细胞呈现不同的细胞命运。这些模式使细胞能够通过读出局部基因表达水平来推断它们在组织或生物体内的总体位置。因此，图案系统被称为编码位置信息，这是最近在信息论框架中正式定义的概念。在这里，我们介绍了一个玩具模型的图案在一个空间维度，这可以被看作是一个扩展Wolpert的范式“法国国旗”模型，图案由几个相互作用，空间耦合的基因受到内在和外在的噪音。我们的模型，一个伊辛自旋系统的变体，使我们能够系统地探索表达模式，最佳编码的位置信息。我们发现，最佳的图案系统使用的位置线索，在法国国旗模型，连同基因-基因的相互作用，以产生组合代码的位置，我们称之为“计数器”的模式。计数器模式也可以通过图灵模型中调用的较长范围的空间相互作用来稳定系统大小或形态发生剂剂量的噪声和变化。这里提出的简单的设置定性捕获许多实验观察到的生物图案化系统的属性，并允许他们在一个单一的，理论上一致的框架进行研究。
英文摘要：
A crucial step in the early development of multicellular organisms involves the establishment of spatial patterns of gene expression which later direct proliferating cells to take on different cell fates. These patterns enable the cells to infer their global position within a tissue or an organism by reading out local gene expression levels. The patterning system is thus said to encode positional information, a concept that was formalized recently in the framework of information theory. Here we introduce a toy model of patterning in one spatial dimension, which can be seen as an extension of Wolpert's paradigmatic "French Flag" model, to patterning by several interacting, spatially coupled genes subject to intrinsic and extrinsic noise. Our model, a variant of an Ising spin system, allows us to systematically explore expression patterns that optimally encode positional information. We find that optimal patterning systems use positional cues, as in the French Flag model, together with gene-gene interactions to generate combinatorial codes for position which we call "Counter" patterns. Counter patterns can also be stabilized against noise and variations in system size or morphogen dosage by longer-range spatial interactions of the type invoked in the Turing model. The simple setup proposed here qualitatively captures many of the experimentally observed properties of biological patterning systems and allows them to be studied in a single, theoretically consistent framework.
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