Modeling the precision and robustness of Hunchback border during Drosophila embryonic development
Modeling the precision and robustness of Hunchback border during Drosophila embryonic development
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DOI：
10.1016/j.jtbi.2008.05.021
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发表时间：
2008-09-21
影响因子：
2
通讯作者：
Forman, Robin
中科院分区：
文献类型：
--
作者：
Hardway, Heather;Mukhopadhyay, Bibhash;Forman, Robin
在果蝇胚胎的前后轴特化过程中，Hunchback（Hb）蛋白以很高的位置精度在胚胎的中点形成一个尖锐的边界。虽然Bicoid（Bcd）是已知的Hb表达的上游调节器，但有证据表明Hb有效地过滤掉从不同Bcd梯度接收的“噪声”数据。我们使用数学模型来探索简单的调节网络，过滤掉这些噪音，以产生精确的Hb边界。我们发现，除了Bcd和Hb，至少有一个自由进化的蛋白质是必要的。自动搜索产生了一些三蛋白质网络的例子，表现出所需的精度。在所有这样的网络中，Hb的扩散比第三种蛋白质慢得多。此外，Hb对第三蛋白质的作用与第三蛋白质对hb的作用相反（即，如果Hb激活第三蛋白质，则第三蛋白质抑制hb表达。反之亦然）。大多数发现的系统满足已知的生物学特性，即Bcd激活Hb，Hb激活其自身的表达。我们发现，所有的网络拓扑结构满足这些约束出现在网络表现出所需的精度。研究这些网络的动力学，我们发现，在一般类的非均匀初始条件下，Bcd可以从系统中消除，这两种蛋白质的时空演化本身就足以重新捕获动力学。我们假设Bcd只需要在空间上干扰第三种蛋白质的梯度，然后在Hb边界的进一步进化中变得不必要。这提供了一个可能的解释，为什么血红蛋白动力学是强大的扰动下的Bcd梯度。在这个假设下，其他蛋白质将能够在我们的模拟中承担Bcd的作用（可能是在进化分歧或过程中的冗余的情况下），唯一的限制是它们积极调节hb。(C)2008爱思唯尔有限公司保留所有权利。
During anterior-posterior axis specification in the Drosophila embryo, the Hunchback (Hb) protein forms a sharp boundary at the mid-point of the embryo with great positional precision. While Bicoid (Bcd) is a known upstream regulator for hb expression, there is evidence to suggest that Hb effectively filters out "noisy" data received from varied Bcd gradients. We use mathematical models to explore simple regulatory networks which filter out such noise to produce a precise Hb boundary. We find that in addition to Bcd and Hb, at least one freely evolving protein is necessary. An automated search yields a number of examples of three-protein networks exhibiting the desired precision. In all such networks, Hb diffuses much slower than the third protein. In addition, the action of Hb on the third protein is the opposite of the action of the third protein on hb (i.e. if Hb activates the third protein, then the third protein inhibits hb expression. and vice versa). Most of the discovered systems satisfy the known biological properties, that Bcd activates hb, and that Hb activates its own expression. We find that all network topologies satisfying these constraints arise among the networks exhibiting the desired precision. investigating the dynamics of these networks, we find that under a general class of non-uniform initial conditions, Bcd can be eliminated from the system and the spatiotemporal evolution of these two proteins alone is sufficient to recapture the dynamics. We hypothesize that Bcd is needed only to spatially disturb the gradient of the third protein, and then becomes unnecessary in the further evolution of the Hb border. This provides a possible explanation as to why the Hb dynamics are robust under perturbations of the Bcd gradient. Under this hypothesis, other proteins would be able to assume the role of Bcd in our simulations (possibly in the case of evolutionary divergences or a redundancy in the process), with the only constraint that they act to positively regulate hb. (C) 2008 Elsevier Ltd. All rights reserved.