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Open Access Research article

Spatiotemporal network motif reveals the biological traits of developmental gene regulatory networks in Drosophila melanogaster

Man-Sun Kim1, Jeong-Rae Kim12, Dongsan Kim1, Arthur D Lander3 and Kwang-Hyun Cho1*

Author affiliations

1 Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Republic of Korea

2 Department of Mathematics, University of Seoul, Seoul, 130-743, Republic of Korea

3 Department of Developmental and Cell Biology and Department of Biomedical Engineering, Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, 92697-2300, USA

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Citation and License

BMC Systems Biology 2012, 6:31  doi:10.1186/1752-0509-6-31

Published: 1 May 2012

Abstract

Background

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.

Results

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.

Conclusions

Taken together, the proposed concept and the simulations can be used to unravel the design principle of developmental gene regulatory networks.