Dynamics of the Dorsal morphogen gradient

The dorsoventral (DV) patterning of the Drosophila embryo depends on the nuclear localization gradient of Dorsal (DI), a protein related to the mammalian NF-[kappa]B transcription factors. Current understanding of how the DI gradient works has been derived from studies of its transcriptional interpretation, but the gradient itself has not been quantified. In particular, it is not known whether the DI gradient is stable or dynamic during the DV patterning of the embryo. To address this question, we developed a mathematical model of the DI gradient and constrained its parameters by experimental data. Based on our computational analysis, we predict that the DI gradient is dynamic and, to a first approximation, can be described as a concentration profile with increasing amplitude and constant shape. These time-dependent properties of the DI gradient are different from those of the Bicoid and MAPK phosphorylation gradients, which pattern the anterior and terminal regions of the embryo. Specifically, the gradient of the nuclear levels of Bicoid is stable, whereas the pattern of MAPK phosphorylation changes in both shape and amplitude. We attribute these striking differences in the dynamics of maternal morphogen gradients to the differences in the initial conditions and chemistries of the anterior, DV, and terminal systems. computational modeling | Drosophila | systems biology | parameter estimation doi/10.1073/pnas.0912395106