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

First Author  Ninkovic J Year  2010
Journal  Neuron Volume  68
Issue  4 Pages  682-94
PubMed ID  21092858 Mgi Jnum  J:167747
Mgi Id  MGI:4879070 Doi  10.1016/j.neuron.2010.09.030
Citation  Ninkovic J, et al. (2010) The transcription factor Pax6 regulates survival of dopaminergic olfactory bulb neurons via crystallin alphaA. Neuron 68(4):682-94
abstractText  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 alphaA (CryalphaA), which blocks apoptosis by inhibition of procaspase-3 activation. Re-expression of CryalphaA fully rescues survival of Pax6-deficient dopaminergic interneurons in vivo and knockdown of CryalphaA 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.
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