Document Detail


E2F1 works as a cell cycle suppressor in mature neurons.
MedLine Citation:
PMID:  18003834     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Li Wang; Rong Wang; Karl Herrup
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  27     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-16     Completed Date:  2007-12-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12555-64     Citation Subset:  IM    
Affiliation:
Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44120, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / genetics*
Calcium-Binding Protein, Vitamin D-Dependent / metabolism
Cell Aging / genetics
Cell Cycle / genetics
Cell Cycle Proteins / genetics,  physiology*
Cell Differentiation / genetics
Cerebellum / growth & development*,  metabolism*,  physiopathology
Cyclin A / genetics,  metabolism
DNA Replication / genetics
E2F1 Transcription Factor / genetics,  physiology*
Female
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutation / genetics
Neurons / metabolism*,  pathology
Proliferating Cell Nuclear Antigen / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
P50-AG08012/AG/NIA NIH HHS; R01-AG24494/AG/NIA NIH HHS; R01-NS20591/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Calcium-Binding Protein, Vitamin D-Dependent; 0/Cell Cycle Proteins; 0/Cyclin A; 0/E2F1 Transcription Factor; 0/E2f1 protein, mouse; 0/Proliferating Cell Nuclear Antigen; 0/calbindin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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