During the first three hours of Drosophila embryogenesis, two conserved signaling pathways act to pattern the dorsal‐ventral (DV) axis: the Dorsal pathway and the Dpp pathway. On the ventral side of the embryo, the transcription factor Dorsal, homologous to NF‐κB, triggers expression of the genes that initiate the DV pattern. Dorsal is present in a nuclear gradient, with the highest concentration at the ventral midline and a steady decay to about 40% of the embryo?s circumference. The Dorsal gradient is initialized via Toll signaling on the ventral side of the embryo; Toll signaling phosphorylates the inhibitor protein Cactus (homologous to I‐κB), marking it for degradation. In the absence of Cactus, Dorsal can enter the nuclei and activate expression of target genes in a concentration‐dependent manner. Dorsal also acts as a transcriptional repressor, limiting some genes to expression on the dorsal half of the embryo. One of those dorsally‐expressed genes is decapentaplegic (dpp), which encodes Dpp, a bone morphogenic protein (BMP) ligand. Dpp is present in a concentration gradient, establishing DV gene patterns beyond Dorsal?s reach. BMP signaling occurs when Dpp binds to the receptor Thickveins (Tkv), phosphorylating the receptor Smad protein MAD. Two phospho‐MAD molecules bind to the co‐Smad Medea; this heterotrimer then enters the nuclei to facilitate expression of target genes. See (A) for a schematic of BMP signaling. Together, the Dorsal gradient and BMP signaling pathway pattern the DV axis of developing Drosophila embryos.
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