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suppressor p53 as a gatekeeper between cellular quiescence, proliferation,
differentiation, and apoptosis. A schematic diagram is provided to summa-
rize this model ( Fig. 4.1 ).
Cell cycle exit has been shown to be crucial for triggering the molecular
machinery and the novel genetic program that drives neuronal differentia-
tion. Therefore, in this scenario, cell cycle regulators including p53 might
play a crucial role in the acquisition of a committed phenotype such as neu-
ronal identity. The differentiation process that neural stem cells undergo
from undifferentiated progenitors into postmitotic neurons or glia occurs
by a progressive loss of multipotentiality and plasticity, and it is closely
p21
GADD-45
PTEN
KLF-4
M
Ac
p53
G 1
G 2
G 0
GAP-43
Coronin 1b
Rab 13
KLF-4?
S
Morphogens
Neurotrophins
Self-renewal/proliferation
Development
Cytokines
Figure 4.1 Diagram shows a hypothetical model of p53 as a gatekeeper between cel-
lular quiescence and differentiation in both neurogenesis (above the dotted line) and
axonal outgrowth (below the dotted line). p53 may regulate cell cycle progression and
reentry (at the center). The activation of a p53-dependent transcriptional program leads
to the regulation of genes involved in stemness and cell cycle regulation (above the
dotted line) and of genes involved in cytoskeleton remodeling (below the dotted line).
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