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Updated: May 16, 2026

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Dissecting the mechanisms of Notch induced hyperplasia
Alexandre Djiane1, Alena Krejci, Frédéric Bernard
1Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
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.
Insights
The Notch pathway
Area of Science:
- Cellular biology
- Developmental biology
- Genetics
Background:
- The Notch pathway's effect on cell proliferation varies by cellular context.
- Notch overactivation in Drosophila wing discs leads to hyperplasia, despite localized inhibitory effects.
Purpose of the Study:
- To identify direct Notch-CSL target genes activated during wing disc hyperplasia.
- To elucidate the molecular mechanisms underlying Notch-induced hyperplasia.
Main Methods:
- Genomic strategies were employed to identify Notch-CSL target genes.
- Analysis of gene expression patterns and regulatory relationships.
Main Results:
- Identified Notch target genes involved in autonomous and non-autonomous regulation of proliferation, growth, and cell death.
- Notch targets display diverse response patterns influenced by feed-forward regulation.
- These targets provide molecular explanations for hyperplasia characteristics.
Conclusions:
- Both the nature of direct Notch targets and their cross-regulatory interactions are crucial for coordinating hyperplasia.
- Understanding these mechanisms offers insights into developmental processes and cancer biology.
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