Kim Man-Sun, Kim Jeong-Rae, Kim Dongsan, Lander Arthur D, Cho Kwang-Hyun
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
BMC Syst Biol. 2012 May 1;6:31. doi: 10.1186/1752-0509-6-31.
Network motifs provided a "conceptual tool" for understanding the functional principles of biological networks, but such motifs have primarily been used to consider static network structures. Static networks, however, cannot be used to reveal time- and region-specific traits of biological systems. To overcome this limitation, we proposed the concept of a "spatiotemporal network motif," a spatiotemporal sequence of network motifs of sub-networks which are active only at specific time points and body parts.
On the basis of this concept, we analyzed the developmental gene regulatory network of the Drosophila melanogaster embryo. We identified spatiotemporal network motifs and investigated their distribution pattern in time and space. As a result, we found how key developmental processes are temporally and spatially regulated by the gene network. In particular, we found that nested feedback loops appeared frequently throughout the entire developmental process. From mathematical simulations, we found that mutual inhibition in the nested feedback loops contributes to the formation of spatial expression patterns.
Taken together, the proposed concept and the simulations can be used to unravel the design principle of developmental gene regulatory networks.
网络基序为理解生物网络的功能原理提供了一种“概念工具”，但此类基序主要用于研究静态网络结构。然而，静态网络无法揭示生物系统的时间和区域特异性特征。为克服这一局限性，我们提出了“时空网络基序”的概念，即仅在特定时间点和身体部位活跃的子网络的网络基序的时空序列。
基于这一概念，我们分析了黑腹果蝇胚胎的发育基因调控网络。我们识别出时空网络基序，并研究了它们在时间和空间上的分布模式。结果，我们发现了基因网络如何在时间和空间上调控关键发育过程。特别是，我们发现嵌套反馈环在整个发育过程中频繁出现。通过数学模拟，我们发现嵌套反馈环中的相互抑制有助于形成空间表达模式。
综上所述，所提出的概念和模拟可用于揭示发育基因调控网络的设计原理。
