TAp73 acts via the bHLH Hey2 to promote long-term maintenance of neural precursors

Curr Biol. 2010 Nov 23;20(22):2058-65. doi: 10.1016/j.cub.2010.10.029. Epub 2010 Nov 11.


Increasing evidence suggests that deficits in adult stem cell maintenance cause aberrant tissue repair and premature aging [1]. While the mechanisms regulating stem cell longevity are largely unknown, recent studies have implicated p53 and its family member p63. Both proteins regulate organismal aging [2-4] as well as survival and self-renewal of tissue stem cells [5-9]. Intriguingly, haploinsufficiency for a third family member, p73, causes age-related neurodegeneration [10]. While this phenotype is at least partially due to loss of the ΔNp73 isoform, a potent neuronal prosurvival protein [11-16], a recent study showed that mice lacking the other p73 isoform, TAp73, have perturbations in the hippocampal dentate gyrus [17], a major neurogenic site in the adult brain. These findings, and the link between the p53 family, stem cells, and aging, suggest that TAp73 might play a previously unanticipated role in maintenance of neural stem cells. Here, we have tested this hypothesis and show that TAp73 ensures normal adult neurogenesis by promoting the long-term maintenance of neural stem cells. Moreover, we show that TAp73 does this by transcriptionally regulating the bHLH Hey2, which itself promotes neural precursor maintenance by preventing premature differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Cell Survival / genetics
  • Cell Survival / physiology
  • Cellular Senescence / genetics
  • Cellular Senescence / physiology
  • Dentate Gyrus / cytology
  • Dentate Gyrus / metabolism
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / physiology
  • Gene Expression Regulation
  • Hippocampus / metabolism
  • Mice
  • Molecular Sequence Data
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neurogenesis / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Olfactory Bulb / cytology
  • Olfactory Bulb / metabolism
  • Phenotype
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Repressor Proteins / physiology*


  • Basic Helix-Loop-Helix Transcription Factors
  • Hey2 protein, mouse
  • Nuclear Proteins
  • Repressor Proteins
  • delta Np73, mouse
  • Fibroblast Growth Factor 2

Associated data

  • GENBANK/AY059384