The Drosophila Gap Gene Network Is Composed of Two Parallel Toggle Switches

Drosophila “gap” genes provide the first response to maternal gradients in the early fly embryo. Gap genes are expressed in a series of broad bands across the embryo during first hours of development. The gene network controlling the gap gene expression patterns includes inputs from maternal gradients and mutual repression between the gap genes themselves. In this study we propose a modular design for the gap gene network, involving two relatively independent network domains. The core of each network domain includes a toggle switch corresponding to a pair of mutually repressive gap genes, operated in space by maternal inputs. The toggle switches present in the gap network are evocative of the phage lambda switch, but they are operated positionally (in space) by the maternal gradients, so the synthesis rates for the competing components change along the embryo anterior-posterior axis. Dynamic model, constructed based on the proposed principle, with elements of fractional site occupancy, required 5–7 parameters to fit quantitative spatial expression data for gap gradients. The identified model solutions (parameter combinations) reproduced major dynamic features of the gap gradient system and explained gap expression in a variety of segmentation mutants.

果蝇缺口基因（Drosophila gap genes）是早期果蝇胚胎中对母源梯度（maternal gradients）信号作出响应的首批基因。在发育的最初数小时内，缺口基因会在胚胎中以一系列宽阔条带的形式进行表达。调控缺口基因表达模式的基因网络，既接收来自母源梯度的信号输入，也依赖缺口基因之间的相互抑制作用。本研究针对缺口基因网络提出了一种模块化设计方案，该方案包含两个相对独立的网络结构域。每个网络结构域的核心包含一个双稳态开关（toggle switch），对应一对相互抑制的缺口基因，由母源信号在空间维度上进行调控。缺口基因网络中的这类双稳态开关与λ噬菌体开关（phage lambda switch）具有相似性，但它们是通过母源梯度在空间位置上进行调控的，因此相互竞争的基因产物的合成速率会沿胚胎的前后轴发生变化。基于该设计原则构建的、包含分数位点占有率（fractional site occupancy）元素的动态模型，仅需5至7个参数即可拟合缺口基因梯度的定量空间表达数据。所得到的模型解（即参数组合）能够复现缺口基因梯度系统的主要动态特征，并可解释多种体节突变体（segmentation mutants）中的缺口基因表达模式。