RTK signaling modulates the Dorsal gradient

• Published in: Development (Cambridge) Vol. 139; no. 16; pp. 3032 - 3039
• Main Authors: Helman, Aharon, Lim, Bomyi, Andreu, María José, Kim, Yoosik, Shestkin, Tatyana, Lu, Hang, Jiménez, Gerardo, Shvartsman, Stanislav Y, Paroush, Ze'ev
• Format: Journal Article
• Language: English
• Published: England Company of Biologists 15.08.2012
• Subjects: Animals; Animals, Genetically Modified; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Body Patterning - genetics; Body Patterning - physiology; Drosophila; Drosophila melanogaster - embryology; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; ErbB Receptors - genetics; ErbB Receptors - metabolism; Feedback, Physiological; Gene Expression Regulation, Developmental; Genes, Insect; HMGB Proteins - genetics; HMGB Proteins - metabolism; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Models, Biological; Mutation; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Phosphoproteins - genetics; Phosphoproteins - metabolism; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Receptors, Invertebrate Peptide - genetics; Receptors, Invertebrate Peptide - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; Signal Transduction; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.075812

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.