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

Abstract

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

A gene regulatory program controlling early Xenopus mesendoderm formation: Network conservation and motifs

“…Of the eight different types of feedforward loops [148] (Figure 2C, Supplemental Table S4), the coherent feedfoward type I is the most abundant. The relative abundance of coherent feedforward type I loops compared to other types of feedforward loops is a feature found in a variety of transcriptional GRNs, including E. coli [148], P. aeruginosa [149], S. cerevisiae [148], and D. melanogaster embryogenesis [150,151]. In our network, approximately three-quarters of identified feedforward loops were coherent type I (Supplemental Table S4).…”

Dynamics and precision in retinoic acid morphogen gradients

“…where gene expression changes continuously in a reliable manner). In the network downstream of Bicoid, where the number of mutually interacting genes is fairly large, and where additional positional information is provided by maternally-derived gradients, there are many potential attractors, both stable and dynamic [47,48]. In the Shh system that patterns the dorsal-ventral (D-V) axis of the neural tube, a more modest (so far) network of inhibitory gene regulatory interactions involving the genes Nkx2.2 Olig2 and Pax6 , creates three stable states [13,46], which correspond to three distinct domains of gene expression that emerge at different distances from the ventral Shh source.…”

A TORC2–Akt Feed-Forward Topology Underlies HER3 Resiliency in HER2-Amplified Cancers

“…As such, TORC2 activates Akt through an incoherent feedforward loop (52, 53) in HER2-amplified cancers and thus the overall topology is best described as a nested or coupled feedforward positive feedback loop. Feedforward loops are widely seen in biologic systems and commonly seen nested within feedback loops, such as during the elaborate and committed programs involved in development (54). In particular, feedforward motifs are known for their stability and rapid signaling response times (53, 55).…”