RT Journal Article
SR Electronic
T1 The Tumor Suppressor p53 Fine-Tunes Reactive Oxygen Species Levels and Neurogenesis via PI3 Kinase Signaling
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 14318
OP 14330
DO 10.1523/JNEUROSCI.1056-13.2013
VO 33
IS 36
A1 Forsberg, Kirsi
A1 Wuttke, Anja
A1 Quadrato, Giorgia
A1 Chumakov, Peter M.
A1 Wizenmann, Andrea
A1 Di Giovanni, Simone
YR 2013
UL http://www.jneurosci.org/content/33/36/14318.abstract
AB Mounting evidence points to a role for endogenous reactive oxygen species (ROS) in cell signaling, including in the control of cell proliferation, differentiation, and fate. However, the function of ROS and their molecular regulation in embryonic mouse neural progenitor cells (eNPCs) has not yet been clarified. Here, we describe that physiological ROS are required for appropriate timing of neurogenesis in the developing telencephalon in vivo and in cultured NPCs, and that the tumor suppressor p53 plays a key role in the regulation of ROS-dependent neurogenesis. p53 loss of function leads to elevated ROS and early neurogenesis, while restoration of p53 and antioxidant treatment partially reverse the phenotype associated with premature neurogenesis. Furthermore, we describe that the expression of a number of neurogenic and oxidative stress genes relies on p53 and that both p53 and ROS-dependent induction of neurogenesis depend on PI3 kinase/phospho-Akt signaling. Our results suggest that p53 fine-tunes endogenous ROS levels to ensure the appropriate timing of neurogenesis in eNPCs. This may also have implications for the generation of tumors of neurodevelopmental origin.