RRC ID 32497
Author Djiane A, Krejci A, Bernard F, Fexova S, Millen K, Bray SJ.
Title Dissecting the mechanisms of Notch induced hyperplasia.
Journal EMBO J.
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.
Volume 32(1)
Pages 60-71
Published 2013-1-9
DOI 10.1038/emboj.2012.326
PII emboj2012326
PMID 23232763
PMC PMC3545308
MeSH Animals Animals, Genetically Modified Cell Division Cell Proliferation Chromatin Immunoprecipitation Drosophila / embryology Drosophila / genetics* Drosophila / growth & development Drosophila / physiology Drosophila Proteins / genetics* Drosophila Proteins / metabolism Female Gene Expression Profiling Gene Expression Regulation, Developmental Genomics Hyperplasia / genetics* Male Oligonucleotide Array Sequence Analysis Phenotype Receptors, Notch / genetics* Receptors, Notch / metabolism Signal Transduction / physiology* Wings, Animal / embryology* Wings, Animal / growth & development Wings, Animal / physiology
IF 10.557
Times Cited 22