Crombach Anton, García-Solache Mónica A, Jaeger Johannes
EMBL/CRG Research Unit in Systems Biology, Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Laboratory for Development and Evolution, University Museum of Zoology and Department of Zoology, Downing Street, Cambridge CB2 3EJ, UK.
Biosystems. 2014 Sep;123:74-85. doi: 10.1016/j.biosystems.2014.06.003. Epub 2014 Jun 6.
Understanding the developmental and evolutionary dynamics of regulatory networks is essential if we are to explain the non-random distribution of phenotypes among the diversity of organismic forms. Here, we present a comparative analysis of one of the best understood developmental gene regulatory networks today: the gap gene network involved in early patterning of insect embryos. We use gene circuit models, which are fitted to quantitative spatio-temporal gene expression data for the four trunk gap genes hunchback (hb), Krüppel (Kr), giant (gt), and knirps (kni)/knirps-like (knl) in the moth midge Clogmia albipunctata, and compare them to equivalent reverse-engineered circuits from our reference species, the vinegar fly Drosophila melanogaster. In contrast to the single network structure we find for D. melanogaster, our models predict four alternative networks for C. albipunctata. These networks share a core structure, which includes the central regulatory feedback between hb and knl. Other interactions are only partially determined, as they differ between our four network structures. Nevertheless, our models make testable predictions and enable us to gain specific insights into gap gene regulation in C. albipunctata. They suggest a less central role for Kr in C. albipunctata than in D. melanogaster, and show that the mechanisms causing an anterior shift of gap domains over time are largely conserved between the two species, although shift dynamics differ. The set of C. albipunctata gene circuit models presented here will be used as the starting point for data-constrained in silico evolutionary simulations to study patterning transitions in the early development of dipteran species.
如果我们要解释表型在生物形态多样性中的非随机分布，那么了解调控网络的发育和进化动态至关重要。在此，我们对当今理解最深入的发育基因调控网络之一进行了比较分析：参与昆虫胚胎早期模式形成的间隙基因网络。我们使用基因电路模型，该模型拟合了摇蚊白纹伊蚊中四个躯干间隙基因驼背（hb）、克鲁佩尔（Kr）、巨人（gt）和克尼普斯（kni）/类克尼普斯（knl）的定量时空基因表达数据，并将它们与我们的参考物种黑腹果蝇的等效逆向工程电路进行比较。与我们在黑腹果蝇中发现的单一网络结构不同，我们的模型预测白纹伊蚊有四种替代网络。这些网络共享一个核心结构，其中包括hb和knl之间的中央调控反馈。其他相互作用仅部分确定，因为它们在我们的四种网络结构之间有所不同。尽管如此，我们的模型做出了可测试的预测，并使我们能够对白纹伊蚊中间隙基因的调控获得具体见解。它们表明，与黑腹果蝇相比，Kr在白纹伊蚊中的作用不那么核心，并且表明尽管转移动态不同，但随着时间的推移导致间隙域向前移动的机制在这两个物种之间基本保守。本文介绍的白纹伊蚊基因电路模型集将用作数据约束的计算机模拟进化的起点，以研究双翅目物种早期发育中的模式转变。
