Whole-Embryo Modeling of Early Segmentation in Drosophila Identifies Robust and Fragile Expression Domains
Whole-Embryo Modeling of Early Segmentation in Drosophila Identifies Robust and Fragile Expression Domains
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DOI：
10.1016/j.bpj.2011.05.060
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发表时间：
2011-07-20
影响因子：
3.4
通讯作者：
Naef, Felix
中科院分区：
文献类型：
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作者：
Bieler, Jonathan;Pozzorini, Christian;Naef, Felix
果蝇胚胎的分割是由mRNA和蛋白质空间模式的动态建立引起的。在这里，我们利用最近的时间mRNA和蛋白质的表达测量胚盘的整个表面校准的动态模型的差距基因网络在整个胚胎皮层。我们建立了差距基因hunchback、Kruppel、giant和knirps的早期mRNA和蛋白质动态模型，将母体Bicoid和Caudal梯度以及合子Tailless和Huckebein蛋白作为调控输入。该模型忠实地捕捉表达模式，其预测从间隙基因突变体进行评估。推断的网络显示了一种基于间隙基因之间的相互抑制的架构，该间隙基因可以在现实的几何形状上稳定地图案化胚胎，但需要复杂的调控，例如涉及Hunchback单体和二聚体的调控。敏感性分析确定了巨人的后域是一个强大的网络中最脆弱的特征之一，并暗示了Bicoid和Hunchback的冗余规则，这可能反映了昆虫间隙基因网络最近的进化变化。
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.