Journal
JOURNAL OF NEUROSCIENCE
Volume 27, Issue 46, Pages 12555-12564Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3681-07.2007
Keywords
cyclin A; PCNA; tumor suppressor; FISH; neuronal differentiation; neuronal death; DNA replication
Categories
Funding
- NIA NIH HHS [P50-AG08012, R01-AG24494, P50 AG008012, R01 AG024494] Funding Source: Medline
- NINDS NIH HHS [R01-NS20591, R01 NS020591] Funding Source: Medline
Ask authors/readers for more resources
Neurons are highly differentiated cells that normally never enter a cell cycle; if they do, the result is usually death, not division. For example, cerebellar granule neurons in staggerer and lurcher mutant mice initiate a cell cycle-like process just before they die. E2F1 is a transcription factor that promotes cell cycle progression. Because E2F1 is also involved in apoptosis, we bred double mutants (E2f1(-/-); staggerer and E2f1(-/-); lurcher) to assess its role in the cell cycle-related death of cerebellar granule cells in vivo. We found neither granule cell cycle initiation nor cell death was significantly altered in either double mutant. However, after postnatal day 10, neurons throughout the CNS of E2f1(-/-) and E2f1(+/-) animals were found to express cell cycle proteins and replicate their DNA. Whereas Map2 and synapsin1 staining are little altered, there is a reduction of calbindin in Purkinje cell dendrites at 1 year of age, suggesting that the mutant cells also undergo a slow, subtle atrophy. These events are cell autonomous, because cultured E2f1(-/-) cortical neurons cycle in vitro, whereas wild-type neurons do not. Our results suggest that, in mature CNS neurons, E2F1 functions as a cell cycle suppressor.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available