Novel interactions between the NF-B and BMP signaling pathways in the Drosophila melanogaster embryo. Sophia Carrell, Gregory Reeves. Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC.

   Many diseases, most notably cancer, occur when cells misinterpret or ignore signals regarding proliferation, migration, and/or apoptosis, implying these signaling pathways must be tightly regulated. Since these same signals are highly conserved between species, we study the regulation of signaling pathways in the context of patterning the dorsal-ventral (DV) axis in the early Drosophila melanogaster embryo.
   The transcription factor Dorsal, homologous to NF-B, is responsible for expression of the genes that generate the DV pattern in the Drosophila embryo. Dorsal is present in the nuclei in a gradient, with the highest concentration at the ventral midline and a steady decay to about 40% of the embryos circumference. This gradient is established on the ventral side of the embryo by signaling through the Toll receptor, which phosphorylates the inhibitor protein Cactus (homologous to I-B), marking it for degradation. In the absence of Cactus, Dorsal is free to enter the nuclei and direct expression of target genes in a concentration-dependent manner. On the dorsal side of the embryo, the bone morphogenic protein (BMP) ligand Dpp is present in a graded fashion, establishing DV gene patterns beyond the spatial range of the Dorsal nuclear gradient.
   Because the Dorsal gradient is essential to correct patterning of the early embryo, there likely exist multiple sets of regulatory loops to ensure proper development in the face of perturbed conditions. Preliminary evidence indicates the existence of such feedback loops through the BMP signaling network. We have found that there is interplay between the gradient of Dorsal, expressed highly on the ventral side of the embryo, and that of BMP signaling, expressed in an opposing gradient with its peak at the dorsal side of the embryo. We believe that the interactions between these two gradients are essential for proper gene positioning along the DV axis of the developing Drosophila embryo.