466998 A Facilitated Diffusion Mechanism Establishes the Drosophila Dorsal Gradient
After using a photoactivatable GFP to show that nucleus-to-nucleus diffusion of Dorsal occurs within the embryo, we extended a previous computational model of Dorsal/Cactus interactions. Our model generically predicts that shuttling occurs in the embryo, and that three experimental perturbations would reveal a shuttling-specific phenotype. First, embryos with a half dose of Dorsal develop gradients that are wider and flatter than normal. Second, slowing Dorsal or Cactus diffusion causes the gradient to widen. And third, expanding the spatial domain where Toll signaling causes Cactus degradation results in a widening or even splitting of the Dorsal gradient. We performed each of these model-guided experiments and observed the predicted phenotypes.
Our results suggest that Cactus plays multiple roles in dorsal-ventral axis specification. Besides its predominant role, which is to maintain Dorsal in the cytoplasm, a secondary, but important role is to shuttle Dorsal towards the ventral midline. Given that this mechanism has been found in other, independent systems, we suggest it may be more prevalent than previously thought.