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PMID:23232763

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Citation

Djiane, A, Krejci, A, Bernard, F, Fexova, S, Millen, K and Bray, SJ (2013) Dissecting the mechanisms of Notch induced hyperplasia. EMBO J. 32:60-71

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.

Links

PubMed PMC3545308 Online version:10.1038/emboj.2012.326

Keywords

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; Wing/embryology; Wing/growth & development; Wing/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:SUH

enables

GO:0000977: RNA polymerase II transcription regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:FRU

involved_in

GO:0044719: regulation of imaginal disc-derived wing size

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:BIB

involved_in

GO:0044719: regulation of imaginal disc-derived wing size

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:CCNE

involved_in

GO:0044719: regulation of imaginal disc-derived wing size

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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