p53 regulates the self-renewal and differentiation of neural precursors.
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.
Armesilla-Diaz
A
A
Department of Cellular and Molecular Physiopathology, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu, 9, 28040 Madrid, Spain.
Bragado
P
P
Del Valle
I
I
Cuevas
E
E
Lazaro
I
I
Martin
C
C
Cigudosa
J C
JC
Silva
A
A
D000818:Animals; D017302:Annexins / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000528:radiation effects; D004622:Embryo, Mammalian; D004815:Epidermal Growth Factor / Q000172:deficiency; D016222:Fibroblast Growth Factor 2 / Q000172:deficiency; D005434:Flow Cytometry / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D019081:O Antigens / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology; D011485:Protein Binding; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000502:physiology*; D014965:X-Rays / Q000009:adverse effects
D017302:Annexins; D005904:Glial Fibrillary Acidic Protein; D019081:O Antigens; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; C462941:beta3 tubulin, mouse; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor