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

Jovica Ninkovic, Luisa Pinto, Stefania Petricca, Alexandra Lepier, Jian Sun, Michael A. Rieger, Timm Schroeder, Ales Cvekl, Jack Favor, Magdalena Götz

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)682-694
Number of pages13
JournalNeuron
Volume68
Issue number4
DOIs
StatePublished - Nov 18 2010

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Crystallins
Olfactory Bulb
Transcription Factors
Interneurons
Neurons
Brain
Dopaminergic Neurons
Caspase 3
Small Interfering RNA
Apoptosis
DNA

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ninkovic, J., Pinto, L., Petricca, S., Lepier, A., Sun, J., Rieger, M. A., ... Götz, M. (2010). The transcription factor Pax6 regulates survival of dopaminergic olfactory bulb neurons via crystallin αA. Neuron, 68(4), 682-694. https://doi.org/10.1016/j.neuron.2010.09.030

The transcription factor Pax6 regulates survival of dopaminergic olfactory bulb neurons via crystallin αA. / Ninkovic, Jovica; Pinto, Luisa; Petricca, Stefania; Lepier, Alexandra; Sun, Jian; Rieger, Michael A.; Schroeder, Timm; Cvekl, Ales; Favor, Jack; Götz, Magdalena.

In: Neuron, Vol. 68, No. 4, 18.11.2010, p. 682-694.

Research output: Contribution to journalArticle

Ninkovic, J, Pinto, L, Petricca, S, Lepier, A, Sun, J, Rieger, MA, Schroeder, T, Cvekl, A, Favor, J & Götz, M 2010, 'The transcription factor Pax6 regulates survival of dopaminergic olfactory bulb neurons via crystallin αA', Neuron, vol. 68, no. 4, pp. 682-694. https://doi.org/10.1016/j.neuron.2010.09.030
Ninkovic, Jovica ; Pinto, Luisa ; Petricca, Stefania ; Lepier, Alexandra ; Sun, Jian ; Rieger, Michael A. ; Schroeder, Timm ; Cvekl, Ales ; Favor, Jack ; Götz, Magdalena. / The transcription factor Pax6 regulates survival of dopaminergic olfactory bulb neurons via crystallin αA. In: Neuron. 2010 ; Vol. 68, No. 4. pp. 682-694.
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