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The Journal of Neuroscience, November 15, 2002, 22(22):9800-9809
p73 Is Required for Survival and Maintenance of CNS Neurons
Christine D.
Pozniak1,
Fanie
Barnabé-Heider1, 3, *,
Vladimir V.
Rymar2, *,
Anna
F.
Lee1, 3,
Abbas F.
Sadikot2, and
Freda D.
Miller1, 3
1 Centre for Neuronal Survival and
2 Division of Neurosurgery, Montreal Neurological
Institute, McGill University, Montreal, Quebec, Canada H3A 2B4,
and 3 Hospital for Sick Children Research Institute,
Toronto, Ontario, Canada M5G 1X8
Here, we show that the p53 family member, p73, is necessary for
survival and long-term maintenance of CNS neurons, including postnatal
cortical neurons. In p73 / animals, cortical neuron number is normal
at birth but decreases significantly by postnatal day 14 (P14)-P16
because of enhanced apoptosis. This decrease continues into
adulthood, when p73/ animals have approximately one-half as many
cortical cells as their wild-type littermates. Cortical neurons express
the  Np73 protein, and overexpression of Np73 isoforms rescues
cortical neurons from diverse apoptotic stimuli. Thus, Np73 isoforms
are survival proteins in cortical neurons, and their deletion causes a
gradual loss of cortical neurons in the weeks and months after birth.
This decrease in CNS neuron number in p73/ animals is not limited
to the cortex; facial motor neuron number is decreased, and postnatal
development of the olfactory bulb is greatly perturbed. These findings,
together with our previous work showing that Np73 is essential for
survival of peripheral sympathetic neurons (Pozniak et al., 2000),
indicate that p73 isoforms are essential survival proteins in CNS as
well as PNS neurons, and that they likely play a role not only during developmental cell death but also in the long-term maintenance of at
least some adult neurons.
Key words:
p73; p53; cortical neurons; facial motor neurons; olfactory bulb; neuronal survival; neuronal development; neuronal
apoptosis; neuronal degeneration; camptothecin; PI3-kinase
*
F.B.-H. and V.V.R. contributed equally to this paper.
Copyright © 2002 Society for Neuroscience 0270-6474/02/22229800-10$05.00/0
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