title: Mapping signaling pathway cross-talk in Drosophila cells.
abstract: During development and homeostasis, cells integrate multiple signals originating either from neighboring cells or systemically. In turn, responding cells can produce signals that act in an autocrine, paracrine, or endocrine manner. Although the nature of the signals and pathways used in cell-cell communication are well characterized, we lack, in most cases, an integrative view of signaling describing the spatial and temporal interactions between pathways (e.g., whether the signals are processed sequentially or concomitantly when two pathways are required for a specific outcome). To address the extent of cross-talk between the major metazoan signaling pathways, we characterized immediate transcriptional responses to either single- or multiple pathway stimulations in homogeneous Drosophila cell lines. Our study, focusing on seven core pathways, epidermal growth factor receptor (EGFR), bone morphogenetic protein (BMP), Jun kinase (JNK), JAK/STAT, Notch, Insulin, and Wnt, revealed that many ligands and receptors are primary targets of signaling pathways, highlighting that transcriptional regulation of genes encoding pathway components is a major level of signaling cross-talk. In addition, we found that ligands and receptors can integrate multiple pathway activities and adjust their transcriptional responses accordingly.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115;
authors.forename: Noemie
authors.initials: N
authors.lastname: Ammeux
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115; bhousden@genetics.med.harvard.edu perrimon@receptor.med.harvard.edu.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Housden
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115;
authors.forename: Andrew
authors.initials: A
authors.lastname: Georgiadis
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115;
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115; Howard Hughes Medical Institute, Boston, MA 02115 bhousden@genetics.med.harvard.edu perrimon@receptor.med.harvard.edu.
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
mesh_terms: D000818:Animals; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D007328:Insulin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; D007328:Insulin; D008070:Lipopolysaccharides
keywords: Drosophila; signaling cross-talk; signaling networks; signaling pathways; transcriptional regulation