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Publication : Different requirements of functional telomeres in neural stem cells and terminally differentiated neurons.

First Author  Lobanova A Year  2017
Journal  Genes Dev Volume  31
Issue  7 Pages  639-647
PubMed ID  28428263 Mgi Jnum  J:242982
Mgi Id  MGI:5907390 Doi  10.1101/gad.295402.116
Citation  Lobanova A, et al. (2017) Different requirements of functional telomeres in neural stem cells and terminally differentiated neurons. Genes Dev 31(7):639-647
abstractText  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.
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