Analysis on gene modular network reveals morphogen-directed development robustness in Drosophila
Analysis on gene modular network reveals morphogen-directed development robustness in Drosophila
复制标题
基因模块网络分析揭示了果蝇形态发生素导向的发育稳健性
DOI：
10.1038/s41421-020-0173-z
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发表时间：
2020-06
期刊：
影响因子：
33.5
通讯作者：
Yun Zhao
中科院分区：
文献类型：
--
作者：
Shuo Zhang;Juan Zhao;Xiangdong Lv;Jialin Fan;Yi Lu;Tao Zeng;Hailong Wu;Luonan Chen;Yun Zhao
遗传鲁棒性是耐受遗传或非遗传干扰并确保表型稳定的重要特征。形态发生素是一类进化上保守的可扩散分子，通过差异调节下游基因表达，以方向依赖或浓度依赖的方式控制组织模式。然而，形态发生导向的基因调控网络是否具有遗传鲁棒性仍然是难以捉摸的。本研究从RNA-seq数据库中收集了果蝇翅盘沿着A-P轴的4217个形态发生应答基因，并将其聚类为12个模块。通过对测量数据应用数学模型，我们构建了一个基因模块网络（GMN），以破译模块的调控相互作用和鲁棒性在形态发生导向的发展。对该GMN的渐近动力学的计算分析表明，这种形态发生导向的GMN是鲁棒的，可以容忍大多数遗传扰动，这已被生物实验进一步验证。此外，除了遗传改变，我们进一步证明，这种形态发生导向的GMN可以很好地容忍非遗传扰动（Hh生产的变化），通过计算分析和实验验证。因此，这些研究结果清楚地表明，形态发生导向的GMN是强大的扰动响应，是重要的果蝇，以确保正确的组织图案在翅盘。
Genetic robustness is an important characteristic to tolerate genetic or nongenetic perturbations and ensure phenotypic stability. Morphogens, a type of evolutionarily conserved diffusible molecules, govern tissue patterns in a direction-dependent or concentration-dependent manner by differentially regulating downstream gene expression. However, whether the morphogen-directed gene regulatory network possesses genetic robustness remains elusive. In the present study, we collected 4217 morphogen-responsive genes along A-P axis of Drosophila wing discs from the RNA-seq data, and clustered them into 12 modules. By applying mathematical model to the measured data, we constructed a gene modular network (GMN) to decipher the module regulatory interactions and robustness in morphogen-directed development. The computational analyses on asymptotical dynamics of this GMN demonstrated that this morphogen-directed GMN is robust to tolerate a majority of genetic perturbations, which has been further validated by biological experiments. Furthermore, besides the genetic alterations, we further demonstrated that this morphogen-directed GMN can well tolerate nongenetic perturbations (Hh production changes) via computational analyses and experimental validation. Therefore, these findings clearly indicate that the morphogen-directed GMN is robust in response to perturbations and is important for Drosophila to ensure the proper tissue patterning in wing disc.
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