Self-Organized Shuttling: Generating Sharp Dorsoventral Polarity in the Early Drosophila Embryo

Morphogen gradients pattern tissues and organs during development. When morphogen production is spatially restricted, diffusion and degradation are sufficient to generate sharp concentration gradients. It is less clear how sharp gradients can arise within the source of a broadly expressed morphogen. A recent solution relies on localized production of an inhibitor outside the domain of morphogen production, which effectively redistributes (shuttles) and concentrates the morphogen within its expression domain. Here, we study how a sharp gradient is established without a localized inhibitor, focusing on early dorsoventral patterning of the Drosophila embryo, where an active ligand and its inhibitor are concomitantly generated in a broad ventral domain. Using theory and experiments, we show that a sharp Toll activation gradient is produced through “self-organized shuttling,” which dynamically relocalizes inhibitor production to lateral regions, followed by inhibitor-dependent ventral shuttling of the activating ligand Spätzle. Shuttling may represent a general paradigm for patterning early embryos. [Display omitted] [Display omitted] ► Pipe expression at oogenesis defines ventral Spätzle processing domain ► The two Spätzle proteolytic products remain associated and can diffuse dorsally ► Toll binding dissociates Spätzle parts, allowing reformation into an inactive complex ► Ventral cleavage of N-terminal region creates ventral flux of active, C-terminal ligand An inhibitor that is produced concomitantly with the active Spätzle ligand helps convert a broad domain of Spätzle processing into a sharp gradient of Toll receptor activation by promoting shuttling and accumulation of active Spätzle ligand to a narrow ventral region.