Document Detail


Unique requirement for Rb/E2F3 in neuronal migration: evidence for cell cycle-independent functions.
MedLine Citation:
PMID:  17452454     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cell cycle regulatory retinoblastoma (Rb) protein is a key regulator of neural precursor proliferation; however, its role has been expanded to include a novel cell-autonomous role in mediating neuronal migration. We sought to determine the Rb-interacting factors that mediate both the cell cycle and migration defects. E2F1 and E2F3 are likely Rb-interacting candidates that we have shown to be deregulated in the absence of Rb. Using mice with compound null mutations of Rb and E2F1 or E2F3, we asked to what extent either E2F1 or E2F3 interacts with Rb in neurogenesis. Here, we report that E2F1 and E2F3 are both functionally relevant targets in neural precursor proliferation, cell cycle exit, and laminar patterning. Each also partially mediates the Rb requirement for neuronal survival. Neuronal migration, however, is specifically mediated through E2F3, beyond its role in cell cycle regulation. This study not only outlines overlapping and distinct functions for E2Fs in neurogenesis but also is the first to establish a physiologically relevant role for the Rb/E2F pathway beyond cell cycle regulation in vivo.
Authors:
Kelly A McClellan; Vladimir A Ruzhynsky; David N Douda; Jacqueline L Vanderluit; Kerry L Ferguson; Danian Chen; Rod Bremner; David S Park; Gustavo Leone; Ruth S Slack
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-04-23
Journal Detail:
Title:  Molecular and cellular biology     Volume:  27     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-18     Completed Date:  2007-08-09     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4825-43     Citation Subset:  IM    
Affiliation:
Department of Cellular and Molecular Medicine, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle*
Cell Movement*
Cell Proliferation
Cell Survival
E2F1 Transcription Factor / metabolism
E2F3 Transcription Factor / metabolism*
Female
Gene Expression Regulation
Interneurons / cytology
Membrane Proteins / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Neurons / cytology*,  metabolism
Oligonucleotide Array Sequence Analysis
Protein Binding
Retinoblastoma Protein / metabolism*
Stem Cells / cytology,  metabolism
Telencephalon / embryology,  metabolism
Chemical
Reg. No./Substance:
0/E2F1 Transcription Factor; 0/E2F3 Transcription Factor; 0/Membrane Proteins; 0/Retinoblastoma Protein; 0/neogenin
Comments/Corrections

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