A two-dimensional simulation model of the bicoid gradient in Drosophila.
A two-dimensional simulation model of the bicoid gradient in Drosophila.
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DOI：
10.1371/journal.pone.0010275
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发表时间：
2010-04-21
期刊：
影响因子：
3.7
通讯作者：
Ma J
中科院分区：
文献类型：
--
作者：
Deng J;Wang W;Lu LJ;Ma J
Bicoid (Bcd) 是一种果蝇形态发生蛋白，负责形成胚胎前部结构的图案。最近的实验研究揭示了对这种形态发生素梯度行为的重要见解，因此有必要开发一种可以概括系统生物学特征的模型，包括其动态和缩放特性。我们提出了果蝇胚胎中 Bcd 梯度动力学的生物学真实二维模型。该模型基于 Bcd 分子与果蝇基因组中非特异性、低亲和力 DNA 位点的平衡结合。它考虑了形成 Bcd 梯度的扩散介质以及产生 Bcd 蛋白的 bcd mRNA 的动态和其他相关特性。我们的模型概括了实验观察到的 Bcd 蛋白梯度的关键特征，包括其缩放特性和发育过程中核浓度的稳定性。我们的模拟模型还允许我们评估其他生物活动对 Bcd 梯度形成的影响，包括早期胚胎中 bcd mRNA 的动态重新分布。我们的模拟结果表明，在我们的模型中，Bcd 蛋白质扩散对于胚胎中指数梯度的形成很重要。本报告中描述的二维模型是一个简单且通用的模拟程序，提供了 Bcd 梯度系统的定量评估。我们的结果表明，Bcd 与非特异性、低亲和力 DNA 位点的结合对于模型中 Bcd 梯度的正确形成具有重要作用。他们证明，可以使用相对较少的参数有效地对高度复杂的生物系统进行建模。
Bicoid (Bcd) is a Drosophila morphogenetic protein responsible for patterning the anterior structures in embryos. Recent experimental studies have revealed important insights into the behavior of this morphogen gradient, making it necessary to develop a model that can recapitulate the biological features of the system, including its dynamic and scaling properties. We present a biologically realistic 2-D model of the dynamics of the Bcd gradient in Drosophila embryos. This model is based on equilibrium binding of Bcd molecules to non-specific, low affinity DNA sites throughout the Drosophila genome. It considers both the diffusion media within which the Bcd gradient is formed and the dynamic and other relevant properties of bcd mRNA from which Bcd protein is produced. Our model recapitulates key features of the Bcd protein gradient observed experimentally, including its scaling properties and the stability of its nuclear concentrations during development. Our simulation model also allows us to evaluate the effects of other biological activities on Bcd gradient formation, including the dynamic redistribution of bcd mRNA in early embryos. Our simulation results suggest that, in our model, Bcd protein diffusion is important for the formation of an exponential gradient in embryos. The 2-D model described in this report is a simple and versatile simulation procedure, providing a quantitative evaluation of the Bcd gradient system. Our results suggest an important role of Bcd binding to non-specific, low-affinity DNA sites in proper formation of the Bcd gradient in our model. They demonstrate that highly complex biological systems can be effectively modeled with relatively few parameters.