Dynamic patterning by the Drosophila pair-rule network reconciles long-germ and short-germ segmentation

Abstract

Drosophila segmentation is a well-established paradigm for developmental pattern formation. However, the later stages of segment patterning, regulated by the “pair-rule” genes, are still not well understood at the system level. Building on established genetic interactions, I construct a logical model of the Drosophila pair-rule system that takes into account the demonstrated stage-specific architecture of the pair-rule gene network. Simulation of this model can accurately recapitulate the observed spatiotemporal expression of the pair-rule genes, but only when the system is provided with dynamic “gap” inputs. This result suggests that dynamic shifts of pair-rule stripes are essential for segment patterning in the trunk and provides a functional role for observed posterior-to-anterior gap domain shifts that occur during cellularisation. The model also suggests revised patterning mechanisms for the parasegment boundaries and explains the aetiology of the even-skipped null mutant phenotype. Strikingly, a slightly modified version of the model is able to pattern segments in either simultaneous or sequential modes, depending only on initial conditions. This suggests that fundamentally similar mechanisms may underlie segmentation in short-germ and long-germ arthropods.

Author summary

Segmentation in insects involves the division of the body into several repetitive units. In Drosophila embryos, all segments are patterned rapidly and simultaneously during early development, in a process known as “long-germ” embryogenesis. In contrast, many insect embryos retain an ancestral or “short-germ” mode of development, in which segments are patterned sequentially, from head to tail, over a period of time. In both types of embryo, the patterning of segment boundaries is regulated by a network of so-called “pair-rule” genes. These networks are thought to be quite divergent due to the different expression patterns observed for the pair-rule genes in each case: regularly spaced arrays of transient stripes in Drosophila, and dynamic expression within a posterior “segment addition zone” in short-germ insects. However, even in Drosophila, a clear understanding of pair-rule patterning has been lacking. Here, I make a computational model of the Drosophila pair-rule network and use simulations to explore how segmentation works. Surprisingly, I find that Drosophila segment patterning relies on pair-rule gene expression moving across cells over time. This conclusion differs from older models of pair-rule patterning but is consistent with the subtly dynamic nature of pair-rule stripes in real embryos, previously described in quantitative studies. I conclude that long-germ and short-germ segmentation involve similar expression dynamics at the level of individual cells, even though they look very different at the level of whole tissues. This suggests that the gene networks involved may be much more conserved than previously thought.