The interpretation of morphogen gradients is a pivotal concept in developmental biology, and several mechanisms have been proposed to explain how gene regulatory networks (GRNs) achieve concentration-dependent responses. However, the number of different mechanisms that may exist for cells to interpret morphogens, and the importance of design features such as feedback or local cell-cell communication, is unclear. A complete understanding of such systems will require going beyond a case-by-case analysis of real morphogen interpretation mechanisms and mapping out a complete GRN 'design space.' Here, we generate a first atlas of design space for GRNs capable of patterning a homogeneous field of cells into discrete gene expression domains by interpreting a fixed morphogen gradient. We uncover multiple very distinct mechanisms distributed discretely across the atlas, thereby expanding the repertoire of morphogen interpretation network motifs. Analyzing this diverse collection of mechanisms also allows us to predict that local cell-cell communication will rarely be responsible for the basic dose-dependent response of morphogen interpretation networks.

中文翻译：

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基因调控网络图谱揭示了多种解释形态发生素梯度的三基因机制。

形态发生素梯度的解释是发育生物学中的一个关键概念，并且已经提出了几种机制来解释基因调控网络 (GRN) 如何实现浓度依赖性反应。然而，细胞解释形态发生素可能存在的不同机制的数量，以及反馈或局部细胞间通讯等设计特征的重要性尚不清楚。对此类系统的完整理解需要超越对真实形态发生解释机制的逐案分析，并绘制出完整的 GRN“设计空间”。在这里，我们为 GRN 生成了第一个设计空间图集，该图集能够通过解释固定的形态发生素梯度将细胞的同质场图案化为离散的基因表达域。我们发现了分布在整个地图集上的多个非常不同的机制，从而扩展了形态原解释网络基序的曲目。分析这种不同的机制集合还使我们能够预测局部细胞 - 细胞通讯很少对形态原解释网络的基本剂量依赖性反应负责。