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The Journal of Neuroscience, May 20, 2009, 29(20):6710-6721; doi:10.1523/JNEUROSCI.5878-08.2009

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Development/Plasticity/Repair
p63 Antagonizes p53 to Promote the Survival of Embryonic Neural Precursor Cells

Chandrasagar B. Dugani,1,2,3 Annie Paquin,1,3 Masashi Fujitani,1,2 David R. Kaplan,2,3,4 and Freda D. Miller1,3,4,5

1Developmental and Stem Cell Biology and 2Cell Biology Programs, Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada, and 3Institute of Medical Science and 4Departments of Molecular Genetics and 5Physiology, University of Toronto, Toronto, Ontario M5G 1L7, Canada

Correspondence should be addressed to Dr. Freda D. Miller, Developmental Biology, Hospital for Sick Children, MaRS Centre, 12-313 TMDT East Tower, 101 College Street, Toronto, ON M5G 1L7, Canada. Email: fredam{at}sickkids.ca

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.

Received Dec. 11, 2008; revised Jan. 23, 2009; accepted March 30, 2009.

Correspondence should be addressed to Dr. Freda D. Miller, Developmental Biology, Hospital for Sick Children, MaRS Centre, 12-313 TMDT East Tower, 101 College Street, Toronto, ON M5G 1L7, Canada. Email: fredam{at}sickkids.ca






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