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Updated: Mar 27, 2026
09:51
Assessing Cell Cycle Progression of Neural Stem and Progenitor Cells in the Mouse Developing Brain after Genotoxic Stress
Published on: May 7, 2014
15.9K
The REST remodeling complex protects genomic integrity during embryonic neurogenesis
Tamilla Nechiporuk1, James McGann1, Karin Mullendorff1
1Vollum Institute, Howard Hughes Medical Institute, Oregon Health and Science University, Portland, United States.
Elife
|January 9, 2016
Summary
Premature loss of the REST repressor in neural progenitors causes DNA damage and brain abnormalities. This highlights REST
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- The transition from neural progenitor to neuron requires down-regulation of the REST transcriptional repressor.
- REST plays a crucial role in repressing neuronal genes during development.
Purpose of the Study:
- To investigate the consequences of premature REST removal from neural progenitors.
- To understand the role of REST in DNA replication and cell cycle regulation.
Main Methods:
- Utilized gene trap mice to eliminate REST expression in neural progenitors.
- Analyzed DNA damage, cell cycle progression, apoptosis, and brain development.
- Examined tumor formation in mice with additional p53 deletion.
Main Results:
- Premature REST loss induced catastrophic DNA damage during S-phase.
- Observed abnormal chromosome separation, apoptosis, and reduced brain size.
- Adult mice lacking REST and p53 developed proneural glioblastomas.
Conclusions:
- REST is essential for proper S-phase dynamics in neural progenitors.
- REST-mediated chromatin remodeling is critical for preventing DNA damage and maintaining genomic stability.
- Complete REST ablation, unlike partial deletion, leads to severe developmental defects and tumorigenesis.
Keywords:
REST complexdevelopmental biologygenomic instabilityknockout animalsmouseneurogenesisrepressionstem cellstranscription factorsMore Related Videos
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