p53 REGULATES THE SELF-RENEWAL AND DIFFERENTIATION OF NEURAL PRECURSORS

被引:73
作者
Armesilla-Diaz, A. [1 ]
Bragado, P. [1 ]
del Valle, I. [1 ]
Cuevas, E. [1 ]
Lazaro, I. [2 ]
Martin, C. [3 ]
Cigudosa, J. C. [3 ]
Silva, A. [1 ]
机构
[1] CSIC, Dept Cellular & Mol Physiopathol, CIB, Madrid 28040, Spain
[2] CSIC, CNB, E-28049 Madrid, Spain
[3] CNIO, Mol Cytogenet Grp, Madrid 28029, Spain
关键词
neurospheres; self-renewal; apoptosis; neural differentiation; STEM-CELL TRANSFORMATION; CENTRAL-NERVOUS-SYSTEM; OLFACTORY-BULB; DNA-DAMAGE; GENOMIC INSTABILITY; PROGENITOR CELLS; APOPTOSIS; CANCER; PROLIFERATION; NEUROGENESIS;
D O I
10.1016/j.neuroscience.2008.10.052
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
During embryo neurogenesis, neurons that originate from stem cells located in the forebrain subventricular zone (SVZ) continuously migrate to the olfactory bulb (OB). However, other authors describe the occurrence of resident stem cells in the OB. In the present work we report that the absence of tumor suppressor protein p53 increases the number of neurosphere-forming cells and the proliferation of stem cells derived from 13.5-day embryo OB. Interestingly, differentiation of p53 knockout-derived neurospheres was biased toward neuronal precursors, suggesting a role for p53 in the differentiation process. Moreover, we demonstrate the relevance of p53 in maintaining chromosomal stability in response to genotoxic insult. Finally, our data show that neurosphere stem cells are highly resistant to long-term epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) deprivation in a p53-independent fashion, and they preserve their differentiation potential. Thus, these data demonstrate that p53 controls the proliferation, chromosomal stability and differentiation pattern of embryonic mouse olfactory bulb stem cells. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:1378 / 1389
页数:12
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