Different requirements of functional telomeres in neural stem cells and terminally differentiated neurons
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Authors
Lobanova, Anastasia
She, Robert
Pieraut, Simon
Clapp, Charlie
Maximov, Anton
Denchi, Eros L.
Issue Date
2017
Type
Article
Language
Keywords
telomeres , neurons , dentate gyrus
Alternative Title
Abstract
Telomeres have been studied extensively in peripheral tissues, but their relevance in the nervous system remains poorly understood. Here, we examine the roles of telomeres at distinct stages of murine brain development by using lineage-specific genetic ablation of TRF2, an essential component of the shelterin complex that protects chromosome ends from the DNA damage response machinery. We found that functional telomeres are required for embryonic and adult neurogenesis, but their uncapping has surprisingly no detectable consequences on terminally differentiated neurons. Conditional knockout of TRF2 in post-mitotic immature neurons had virtually no detectable effect on circuit assembly, neuronal gene expression, and the behavior of adult animals despite triggering massive end-to-end chromosome fusions across the brain. These results suggest that telomeres are dispensable in terminally differentiated neurons and provide mechanistic insight into cognitive abnormalities associated with aberrant telomere length in humans.
Description
Citation
Lobanova, A., She, R., Pieraut, S., Clapp, C., Maximov, A., & Denchi, E. L. (2017). Different requirements of functional telomeres in neural stem cells and terminally differentiated neurons. Genes & Development, 31(7), 639�"647. doi:10.1101/gad.295402.116
Publisher
License
Creative Commons Attribution-NonCommercial 4.0 International
Journal
Volume
Issue
PubMed ID
ISSN
0890-9369