Mi-2/NuRD complex protects stem cell progeny from mitogenic Notch signaling.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30694174.
- Also identified by DOI 10.7554/eLife.41637 and PMC identifier 6379090.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>Drosophila</i> 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, <i>E(spl)mγ</i>, 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, <i>E(spl)mγ</i> 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.
Medical subject headings
- Adenosine Triphosphatases
- Autoantigens
- Basic Helix-Loop-Helix Proteins
- Drosophila Proteins
- Drosophila melanogaster
- Hyperplasia
- Neural Stem Cells
- Receptors, Notch
- Repressor Proteins