Document Detail


Cell-autonomous and non-cell-autonomous functions of the Rb tumor suppressor in developing central nervous system.
MedLine Citation:
PMID:  11432828     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The retinoblastoma tumor suppressor (RB) plays an important role in the regulation of cell cycle progression and terminal differentiation of many cell types. Rb(-/-) mouse embryos die at midgestation with defects in cell cycle regulation, control of apoptosis and terminal differentiation. However, chimeric mice composed of wild-type and Rb-deficient cells are viable and show minor abnormalities. To determine the role of Rb in development more precisely, we analyzed chimeric embryos and adults made with marked Rb(-/-) cells. Like their germline Rb(-/-) counterparts, brains of midgestation chimeric embryos exhibited extensive ectopic S-phase entry. In Rb-mutants, this is accompanied by widespread apoptosis. However, in chimeras, the majority of Rb-deficient cells survived and differentiated into neuronal fates. Rescue of Rb(-/-) neurons in the presence of wild-type cells occurred after induction of the p53 pathway and led to accumulation of cells with 4n DNA content. Therefore, the role of Rb during development can be divided into a cell-autonomous function in exit from the cell cycle and a non-cell-autonomous role in the suppression of apoptosis and induction of differentiation.
Authors:
M M Lipinski; K F Macleod; B O Williams; T L Mullaney; D Crowley; T Jacks
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The EMBO journal     Volume:  20     ISSN:  0261-4189     ISO Abbreviation:  EMBO J.     Publication Date:  2001 Jul 
Date Detail:
Created Date:  2001-07-02     Completed Date:  2001-08-09     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  3402-13     Citation Subset:  IM    
Affiliation:
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Apoptosis
Brain / embryology,  physiology*
Cell Cycle / physiology*
Cell Death
Cell Differentiation
Chimera
Embryo, Mammalian / cytology,  physiology*
Embryonic and Fetal Development*
Female
Fetal Death
Genes, Retinoblastoma*
Gestational Age
In Situ Nick-End Labeling
Mice
Mice, Knockout
Mice, Transgenic
Pregnancy
Retinoblastoma Protein / deficiency,  genetics,  metabolism*
S Phase
beta-Galactosidase / analysis,  genetics
Chemical
Reg. No./Substance:
0/Retinoblastoma Protein; EC 3.2.1.23/beta-Galactosidase
Comments/Corrections

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


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