A reaction-diffusion network model predicts a dual role of Cactus/IκB to regulate Dorsal/NFκB nuclear translocation in Drosophila

Dorsal-ventral patterning of the Drosophila embryo depends on NFκB superfamily transcription factor Dorsal (Dl). Toll receptor activation signals for degradation IκB inhibitor Cactus (Cact), leading to a ventral-to-dorsal nuclear Dl gradient. Cact is critical import, as it binds and prevents from entering nuclei. Quantitative analysis cact mutants revealed an additional function promote translocation in ventral regions embryo. To investigate this dual role, we developed predictive model based reaction-diffusion regulatory network. This network distinguishes non-uniform Toll-dependent import degradation, Toll-independent processes reversible nuclear-cytoplasmic flow. In addition, incorporates translational control levels by Dl. Our successfully reproduces wild-type data emulates gradient mutant dl allelic combinations. results indicate that role dynamics Dl-Cact trimers along dorsal-ventral axis: absence activation, free retain cytoplasm, limiting flow into nucleus; ventral-lateral regions, are recruited predominant signaling complexes translocation. Simulations suggest balance between key reproduce full assortment effects. Considering high evolutionary conservation these pathways, our should contribute understanding NFκB/c-Rel other contexts such vertebrate immune system disease.