Mi-2/NuRD complex protects stem cell progeny from mitogenic Notch signalling
- University of Cambridge, United Kingdom
Abstract
To progress towards differentiation, progeny of stem cells need to extinguish expression of stem cell maintenance genes. Failures in such mechanisms can drive tumorigenesis. In Drosophila neural stem cell (NSC) lineages, excessive Notch signalling results in supernumerary NSCs causing hyperplasia. However, onset of hyperplasia is considerably delayed implying there are mechanisms that resist the mitogenic signal. Monitoring the live expression of a Notch target gene, E(spl)mγ, revealed that normal attenuation is still initiated in the presence of excess Notch activity so that re-emergence of NSC properties occurs only in older progeny. Screening for factors responsible, we found that depletion of Mi-2/NuRD ATP remodeling complex dramatically enhanced Notch-induced hyperplasia. Under these conditions, E(spl)mγ was no longer extinguished in NSC progeny. We propose that Mi-2 is required for decommissioning stem cell enhancers in their progeny, enabling the switch towards more differentiated fates and rendering them insensitive to mitogenic factors such as Notch.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Examples of movies have been provided for Figures 2 and 4
Article and author information
Author details
Julia Falo Sanjuan
Funding
Medical Research Council
- Evanthia Zacharioudaki
- Sarah Bray
Wellcome
- Julia Falo Sanjuan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Michael Buszczak, University of Texas Southwestern Medical Center, United States
Version history
- Received: September 4, 2018
- Accepted: January 15, 2019
- Accepted Manuscript published: January 29, 2019 (version 1)
- Version of Record published: February 18, 2019 (version 2)
Copyright
© 2019, Zacharioudaki et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Mi-2/NuRD complex protects stem cell progeny from mitogenic Notch signalling
eLife 8:e41637.
https://doi.org/10.7554/eLife.41637
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