p73 is an essential regulator of neural stem cell maintenance in embryonal and adult CNS neurogenesis

Cell Death Differ. 2010 Dec;17(12):1816-29. doi: 10.1038/cdd.2010.131.


The p53 family member p73 is essential for brain development, but its precise role and scope remain unclear. Global p73 deficiency determines an overt and highly penetrant brain phenotype marked by cortical hypoplasia with ensuing hydrocephalus and hippocampal dysgenesis. The ΔNp73 isoform is known to function as a prosurvival factor of mature postmitotic neurons. In this study, we define a novel essential role of p73 in the regulation of the neural stem cell compartment. In both embryonic and adult neurogenesis, p73 has a critical role in maintaining an adequate neurogenic pool by promoting self-renewal and proliferation and inhibiting premature senescence of neural stem and early progenitor cells. Thus, products of the p73 gene locus are essential maintenance factors in the central nervous system, whose broad action stretches across the entire differentiation arch from stem cells to mature postmitotic neurons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology
  • Adult Stem Cells / metabolism
  • Animals
  • Cell Differentiation
  • Cell Survival
  • Cellular Senescence
  • Central Nervous System / cytology*
  • Central Nervous System / embryology*
  • Central Nervous System / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Hydrocephalus / pathology
  • Mice
  • Mice, Knockout
  • Mitosis
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Neurogenesis*
  • Neurons / cytology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Receptors, Notch / metabolism
  • S Phase
  • SOXB1 Transcription Factors / metabolism
  • Signal Transduction
  • Tumor Protein p73
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Tumor Suppressor Proteins / physiology*


  • DNA-Binding Proteins
  • Nuclear Proteins
  • Receptors, Notch
  • SOXB1 Transcription Factors
  • Trp73 protein, mouse
  • Tumor Protein p73
  • Tumor Suppressor Proteins