The transcription factor Pax6 regulates survival of dopaminergic olfactory bulb neurons via crystallin αA

Neuron. 2010 Nov 18;68(4):682-94. doi: 10.1016/j.neuron.2010.09.030.


Most neurons in the adult mammalian brain survive for the entire life of an individual. However, it is not known which transcriptional pathways regulate this survival in a healthy brain. Here, we identify a pathway regulating neuronal survival in a highly subtype-specific manner. We show that the transcription factor Pax6 expressed in dopaminergic neurons of the olfactory bulb regulates the survival of these neurons by directly controlling the expression of crystallin αA (CryαA), which blocks apoptosis by inhibition of procaspase-3 activation. Re-expression of CryαA fully rescues survival of Pax6-deficient dopaminergic interneurons in vivo and knockdown of CryαA by shRNA in wild-type mice reduces the number of dopaminergic OB interneurons. Strikingly, Pax6 utilizes different DNA-binding domains for its well-known role in fate specification and this role of regulating the survival of specific neuronal subtypes in the mature, healthy brain.

Publication types

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

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Survival / genetics
  • Cell Survival / physiology
  • Crystallins / genetics
  • Crystallins / physiology*
  • Dopamine / physiology*
  • Eye Proteins / genetics
  • Eye Proteins / physiology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / physiology*
  • Olfactory Bulb / cytology
  • Olfactory Bulb / metabolism
  • Olfactory Bulb / physiology*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / physiology*
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*


  • CRYAA protein, human
  • Crystallins
  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Repressor Proteins
  • Dopamine