title: Dissecting the mechanisms of Notch induced hyperplasia.
abstract: The outcome of the Notch pathway on proliferation depends on cellular context, being growth promotion in some, including several cancers, and growth inhibition in others. Such disparate outcomes are evident in Drosophila wing discs, where Notch overactivation causes hyperplasia despite having localized inhibitory effects on proliferation. To understand the underlying mechanisms, we have used genomic strategies to identify the Notch-CSL target genes directly activated during wing disc hyperplasia. Among them were genes involved in both autonomous and non-autonomous regulation of proliferation, growth and cell death, providing molecular explanations for many characteristics of Notch induced wing disc hyperplasia previously reported. The Notch targets exhibit different response patterns, which are shaped by both positive and negative feed-forward regulation between the Notch targets themselves. We propose, therefore, that both the characteristics of the direct Notch targets and their cross-regulatory relationships are important in coordinating the pattern of hyperplasia.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Djiane
authors.forename: Alena
authors.initials: A
authors.lastname: Krejci
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bernard
authors.forename: Silvie
authors.initials: S
authors.lastname: Fexova
authors.forename: Katherine
authors.initials: K
authors.lastname: Millen
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Bray
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002455:Cell Division; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D004330:Drosophila / Q000196:embryology / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D023281:Genomics; D006965:Hyperplasia / Q000235:genetics*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014921:Wings, Animal / Q000196:embryology* / Q000254:growth & development / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch