RTK signaling modulates the Dorsal gradient. Author Aharon Helman, Bomyi Lim, María Andreu, Yoosik Kim, Tatyana Shestkin, Hang Lu, Gerardo Jiménez, Stanislav Shvartsman, Ze'ev Paroush Publication Year 2012 Type Journal Article Abstract The dorsoventral (DV) axis of the Drosophila embryo is patterned by a nuclear gradient of the Rel family transcription factor, Dorsal (Dl), that activates or represses numerous target genes in a region-specific manner. Here, we demonstrate that signaling by receptor tyrosine kinases (RTK) reduces nuclear levels and transcriptional activity of Dl, both at the poles and in the mid-body of the embryo. These effects depend on wntD, which encodes a Dl antagonist belonging to the Wingless/Wnt family of secreted factors. Specifically, we show that, via relief of Groucho- and Capicua-mediated repression, the Torso and EGFR RTK pathways induce expression of WntD, which in turn limits Dl nuclear localization at the poles and along the DV axis. Furthermore, this RTK-dependent control of Dl is important for restricting expression of its targets in both contexts. Thus, our results reveal a new mechanism of crosstalk, whereby RTK signals modulate the spatial distribution and activity of a developmental morphogen in vivo. Keywords Animals, Drosophila Proteins, Gene Expression Regulation, Developmental, Mutation, Receptor Protein-Tyrosine Kinases, Signal Transduction, Models, Biological, Genes, Insect, Drosophila melanogaster, Transcription Factors, Body Patterning, Repressor Proteins, Nuclear Proteins, Phosphoproteins, Animals, Genetically Modified, Basic Helix-Loop-Helix Transcription Factors, Receptor, Epidermal Growth Factor, HMGB Proteins, Feedback, Physiological, Intracellular Signaling Peptides and Proteins, Receptors, Invertebrate Peptide Journal Development Volume 139 Issue 16 Pages 3032-9 Date Published 08/2012 Alternate Journal Development Google ScholarBibTeXEndNote X3 XML