Data from: Analyzing negative feedback using a synthetic gene network expressed in the Drosophila melanogaster embryo

Background: A complex network of gene interactions controls gene regulation throughout development and the life of the organisms. Insights can be made into these processes by studying the functional interactions (or “motifs”) which make up these networks. Results: We sought to understand the functionality of one of these network motifs, negative feedback, in a multi-cellular system. This was accomplished using a synthetic network expressed in the Drosophila melanogaster embryo using the yeast proteins Gal4 (a transcriptional activator) and Gal80 (an inhibitor of Gal4 activity). This network is able to produce an attenuation or shuttling phenotype depending on the Gal80/Gal4 ratio. This shuttling behavior was validated by expressing Gal3, which inhibits Gal80, to produce a localized increase in free Gal4 and therefore signaling. Mathematical modeling was used to demonstrate the capacity for negative feedback to produce these varying outputs. Conclusions: The capacity of a network motif to exhibit different phenotypes due to minor changes to the network in multi-cellular systems was shown. This work demonstrates the importance of studying network motifs in multi-cellular systems.研究背景：基因互作构成的复杂网络，调控着生物体整个发育周期与生命进程中的基因表达。解析构成这类网络的功能互作单元（或称“基序（motifs）”），可为上述生命过程提供研究视角。 研究结果：本研究旨在解析多细胞系统中这类网络基序之一——负反馈的功能。我们通过在黑腹果蝇（Drosophila melanogaster）胚胎中表达合成网络完成该研究，该合成网络利用了酵母蛋白Gal4（转录激活因子）与Gal80（Gal4活性抑制剂）。该网络可根据Gal80与Gal4的比例，呈现衰减或穿梭表型。通过表达抑制Gal80的Gal3，使游离Gal4水平局部升高，进而增强信号转导，验证了该穿梭行为。此外，本研究通过数学建模证实了负反馈可产生上述多样化输出的能力。 研究结论：本研究证实，在多细胞系统中，网络基序可因网络的细微改变而呈现不同表型；同时证明了在多细胞系统中研究网络基序的重要性。