Neural precursor cells self-renew and differentiate throughout development and in response to neural injury in the adult brain. The DNA damage response in NPCs has yet to be characterized.
Patients with defective nucleotide excision repair (NER) demonstrate neurodegeneration
dismyelination, and microcephaly, suggesting a potential link to defective NPC function with accumulating DNA damage. We observed reduced self-renewal in Csbm/m and Xpam/m NPCs in response to UV damage. Serial passaging resulted in exhaustion of Csbm/m NPCs in the absence of exogenous DNA damage. In vitro neuronal differentiation resulted in abnormal neuritigenesis after UV DNA damage in Csbm/m NPCs, suggesting defects in the terminal differentiation process. Taken together, the results indicate that DNA damage can modulate the apoptotic, self-renewal and differentiation fates of NPCs.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/25785 |
| Date | 10 January 2011 |
| Creators | Sacco, Raffaele |
| Contributors | Laposa, Rebecca |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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