p73 is required for survival and maintenance of CNS neurons.
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 DeltaNp73alpha protein, and overexpression of DeltaNp73 isoforms rescues cortical neurons from diverse apoptotic stimuli. Thus, DeltaNp73 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 DeltaNp73 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.
Pozniak
Christine D
CD
Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4.
Barnabé-Heider
Fanie
F
Rymar
Vladimir V
VV
Lee
Anna F
AF
Sadikot
Abbas F
AF
Miller
Freda D
FD
D000818:Animals; D017209:Apoptosis; D001933:Brain Stem / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000235:genetics; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D016147:Genes, Tumor Suppressor; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases