The proposed study aims to determine how the Toll-Dorsal (D1) signaling pathway forms molecular gradients that act to control dorsoventral body axis patterning of the early Drosophila embryo. A dorsoventral gradient of nuclear localized D1, a member of the Rel family of transcription factors, results from activation of the Toll receptors on the ventral surfaces of the early Drosophila embryo. Though it is clear that the D1 gradient mediates differentiation of the mesoderm, neuroectoderm, and dorsal ectoderm through differential transcriptional regulation, it remains unclear how this gradient is established. For example, it is not known whether the D1 gradient results from the absolute number of fully activated To11 receptors (""""""""integrating"""""""" model). Furthermore, diffusion of Toll-D1 signaling components may also contribute to gradient formation. This research proposal describes three specific aims: (i) to determine whether partially activated To11 receptors can specify a peak threshold and thus whether cells can integrate the partially activated To11 receptors can specify a peak threshold and thus whether cells can integrate the number of both fully and partially activated receptors to generate differential signaling responses: (ii) to determine whether diffusion of the Toll receptor and/or intracellular signaling components contribute to the formation of the D1 nuclear gradient; and (iii) to identify other components of the To11-D1 signaling pathway which may also contribute to the establishment of this gradient.
