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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Animals, Genetically Modified
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Body Patterning / genetics
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Body Patterning / physiology
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / embryology*
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Drosophila melanogaster / genetics
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Drosophila melanogaster / metabolism*
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ErbB Receptors / genetics
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ErbB Receptors / metabolism
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Feedback, Physiological
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Gene Expression Regulation, Developmental
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Genes, Insect
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HMGB Proteins / genetics
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HMGB Proteins / metabolism
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Models, Biological
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Mutation
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / metabolism*
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Receptors, Invertebrate Peptide / genetics
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Receptors, Invertebrate Peptide / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Signal Transduction
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Drosophila Proteins
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HMGB Proteins
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Intracellular Signaling Peptides and Proteins
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Nuclear Proteins
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Phosphoproteins
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Receptors, Invertebrate Peptide
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Repressor Proteins
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Transcription Factors
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WntD protein, Drosophila
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cic protein, Drosophila
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dl protein, Drosophila
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gro protein, Drosophila
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Egfr protein, Drosophila
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ErbB Receptors
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Receptor Protein-Tyrosine Kinases
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tor protein, Drosophila