title: Genetic regulation and function of epidermal growth factor receptor signalling in patterning of the embryonic Drosophila brain.
abstract: The specification of distinct neural cell types in central nervous system development crucially depends on positional cues conferred to neural stem cells in the neuroectoderm. Here, we investigate the regulation and function of the epidermal growth factor receptor (EGFR) signalling pathway in early development of the Drosophila brain. We find that localized EGFR signalling in the brain neuroectoderm relies on a neuromere-specific deployment of activating (Spitz, Vein) and inhibiting (Argos) ligands. Activated EGFR controls the spatially restricted expression of all dorsoventral (DV) patterning genes in a gene- and neuromere-specific manner. Further, we reveal a novel role of DV genes-ventral nervous system defective (vnd), intermediate neuroblast defective (ind), Nkx6-in regulating the expression of vein and argos, which feed back on EGFR, indicating that EGFR signalling stands not strictly atop the DV patterning genes. Within this network of genetic interactions, Vnd acts as a positive EGFR feedback regulator. Further, we show that EGFR signalling becomes dependent on single-minded-expressing midline cells in the posterior brain (tritocerebrum), but remains midline-independent in the anterior brain (deuto- and protocerebrum). Finally, we demonstrate that activated EGFR controls the proper formation of brain neuroblasts by regulating the number, survival and proneural gene expression of neuroectodermal progenitor cells. These data demonstrate that EGFR signalling is crucially important for patterning and early neurogenesis of the brain.
authors.affiliation: Institute of Genetics, University of Mainz, 55099 Mainz, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Jussen
authors.affiliation: Institute of Genetics, University of Mainz, 55099 Mainz, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: von Hilchen
authors.affiliation: Institute of Genetics, University of Mainz, 55099 Mainz, Germany urbach@uni-mainz.de.
authors.forename: Rolf
authors.identifier: 0000-0003-1374-4028
authors.initials: R
authors.lastname: Urbach
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D019521:Body Patterning; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D054258:Neural Plate / Q000378:metabolism; D020880:Neuregulins / Q000378:metabolism; D055495:Neurogenesis; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D018010:Receptors, Invertebrate Peptide / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D005136:Eye Proteins; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020880:Neuregulins; D009687:Nuclear Proteins; D018010:Receptors, Invertebrate Peptide; D014157:Transcription Factors; C089449:sim protein, Drosophila; C094797:vnd protein, Drosophila; C075638:aos protein, Drosophila; C076026:spi protein, Drosophila; C102104:vn protein, Drosophila; C066532:Egfr protein, Drosophila
keywords: argos; brain neuroblasts; dorsoventral patterning genes; epidermal growth factor receptor; rhomboid; vein