The topology of the regulatory interactions predicts the expression pattern of the segment polarity genes in Drosophila melanogaster
The topology of the regulatory interactions predicts the expression pattern of the segment polarity genes in Drosophila melanogaster
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DOI：
10.1016/s0022-5193(03)00035-3
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发表时间：
2003-07-07
影响因子：
2
通讯作者：
Othmer, HG
中科院分区：
文献类型：
--
作者：
Albert, R;Othmer, HG
果蝇节段极性基因的表达是由配对规则基因产物的预模式启动的，并由胚胎发育的几个阶段中的调控相互作用网络维持。对基于微分方程的基因互作模型的分析表明，这些基因的野生型表达模式可以在广泛的动力学参数范围内获得，这表明稳态是由网络的拓扑结构和组分之间的调控相互作用的类型决定的，而不是由速率定律的详细形式决定的。为了研究这一点，我们提出并分析了这个网络的布尔模型，该模型基于mRNA和蛋白质水平的二进制开/关表示，其中相互作用被表示为逻辑函数。在这个模型中，基因表达的时空模式是由网络的拓扑结构和组件的存在与否决定的，而不是由mRNA和蛋白质的绝对水平以及它们相互作用的功能细节决定的。该模型能够再现野生型基因表达模式，以及在过表达实验和各种突变体中观察到的异位表达模式。此外，我们还显式计算了网络的所有稳态，并确定了每个稳态的吸引域。该模型对片段极性基因网络的功能提供了重要的见解，例如无翅和草率的配对基因的关键作用，以及网络纠正前模式中错误的能力。(C)2003爱思唯尔科学有限公司。保留所有权利。
Expression of the Drosophila segment polarity genes is initiated by a pre-pattern of pair-rule gene products and maintained by a network of regulatory interactions throughout several stages of embryonic development. Analysis of a model of gene interactions based on differential equations showed that wild-type expression patterns of these genes can be obtained for a wide range of kinetic parameters, which suggests that the steady states are determined by the topology of the network and the type of regulatory interactions between components, not the detailed form of the rate laws. To investigate this, we propose and analyse a Boolean model of this network which is based on a binary ON/OFF representation of mRNA and protein levels, and in which the interactions are formulated as logical functions. In this model the spatial and temporal patterns of gene expression are determined by the topology of the network and whether components are present or absent, rather than the absolute levels of the mRNAs and proteins and the functional details of their interactions. The model is able to reproduce the wild-type gene expression patterns, as well as the ectopic expression patterns observed in overexpression experiments and various mutants. Furthermore, we compute explicitly all steady states of the network and identify the basin of attraction of each steady state. The model gives important insights into the functioning of the segment polarity gene network, such as the crucial role of the wingless and sloppy paired genes, and the network's ability to correct errors in the pre-pattern. (C) 2003 Elsevier Science Ltd. All rights reserved.