Modeling Dorsal Feedback Interactions in the Developing Embryo. Michael D. O'Connell, Gregory T. Reeves. Department of Chemical & Biomolecular Engineering, NC State University, Raleigh, NC.

   Dorsoventral axis polarity in the developing embryo is largely determined by the transcription factor Dorsal prior to gastrulation. Dorsal acts as a morphogen by promoting gene expression along the ventral half of the embryo causing cells to adopt certain fates, leading to patterning of the endoderm, mesoderm, and neurogenic ectoderm. The classical morphogen hypothesis suggests that Dorsal targets are regulated in a concentration-dependent fashion, and that changing the concentration of Dorsal by altering its dosage will disturb the spatial pattern of target gene expression. However, recent work has shown (1) that the Dorsal concentration gradient is not simply proportional to the number of Dorsal alleles and (2) that gene expression is robust with respect to changes in the Dorsal gradient. These results are not explainable under the current model. In light of the fact that feedback loops provide many gene regulatory networks with robustness, we are building a more comprehensive model that includes possible regulatory interactions between Dorsal and its target genes. Our first step was to illuminate the effects of Cactus, a suspected Dorsal target that is also a Dorsal inhibitor, in regulating the shape of the Dorsal gradient. This and other potential feedback mechanisms, such as a Dorsal-Dpp interaction, may further explain experimental results. Developing a more accurate model will allow us to predict the outcomes of future studies and lead us to a deeper understanding of this complex system.