The Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Biophys J. 2011 Jul 20;101(2):287-96. doi: 10.1016/j.bpj.2011.05.060.
Segmentation of the Drosophila melanogaster embryo results from the dynamic establishment of spatial mRNA and protein patterns. Here, we exploit recent temporal mRNA and protein expression measurements on the full surface of the blastoderm to calibrate a dynamical model of the gap gene network on the entire embryo cortex. We model the early mRNA and protein dynamics of the gap genes hunchback, Kruppel, giant, and knirps, taking as regulatory inputs the maternal Bicoid and Caudal gradients, plus the zygotic Tailless and Huckebein proteins. The model captures the expression patterns faithfully, and its predictions are assessed from gap gene mutants. The inferred network shows an architecture based on reciprocal repression between gap genes that can stably pattern the embryo on a realistic geometry but requires complex regulations such as those involving the Hunchback monomer and dimers. Sensitivity analysis identifies the posterior domain of giant as among the most fragile features of an otherwise robust network, and hints at redundant regulations by Bicoid and Hunchback, possibly reflecting recent evolutionary changes in the gap-gene network in insects.
果蝇胚胎的分割是由空间 mRNA 和蛋白质模式的动态建立所导致的。在这里，我们利用最近在整个胚胎皮层上对全面胚层进行的时间 mRNA 和蛋白质表达测量，来校准缺口基因网络的动力学模型。我们对缺口基因 hunchback、Kruppel、giant 和 knirps 的早期 mRNA 和蛋白质动力学进行建模，将母体 Bicoid 和 Caudal 梯度以及合子 Tailless 和 Huckebein 蛋白作为调控输入。该模型忠实地捕捉到了表达模式，并且从缺口基因突变体中评估了其预测。推断出的网络显示出一种基于缺口基因之间的相互抑制的架构，这种架构可以在现实的几何形状上稳定地给胚胎进行模式化，但需要复杂的调节，例如涉及 Hunchback 单体和二聚体的调节。敏感性分析确定 giant 的后域是一个稳健网络中最脆弱的特征之一，并暗示了 Bicoid 和 Hunchback 的冗余调节，这可能反映了昆虫中缺口基因网络的最近进化变化。
