p63 Antagonizes p53 to Promote the Survival of Embryonic Neural Precursor Cells

The molecular mechanisms that regulate survival of embryonic neural precursors are still relatively ill-defined. Here, we have asked whether the p53 family member p63 plays any role during this developmental window, focusing on the embryonic cerebral cortex. We show that genetic knockdown of p63 either in culture or in the embryonic telencephalon causes apoptosis of cortical precursors and newly born cortical neurons, and that this can be rescued by expression of Delta Np63, but not TAp63 isoforms. This cortical precursor apoptosis is the consequence of deregulated p53 activity, since both basal precursor apoptosis and that induced by loss of p63 are rescued by coincident genetic silencing of p53. Finally, we demonstrate that the third p53 family member, Delta Np73, does not regulate survival of cortical precursor cells, but that it collaborates with Delta Np63 to ensure the survival of newly born cortical neurons. Thus, the balance of Delta Np63 versus p53 determines the life versus death of embryonic cortical precursors, a role that these p53 family members may well play in other populations of developing and/or adult neural precursors.