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Ninkovic, J. ; Pinto, L. ; Petricca, S. ; Lepier, A.* ; Sun, J.* ; Rieger, M. ; Schroeder, T. ; Cvekl, A.* ; Favor, J. ; Götz, M.

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

Neuron 68, 682-694 (2010)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter B-CRYSTALLIN; ADULT NEUROGENESIS; MAMMALIAN TELENCEPHALON; PARKINSONS-DISEASE; CEREBRAL-CORTEX; GENETIC-CONTROL; KNOCKOUT MICE; PAIRED DOMAIN; MUS-MUSCULUS; STEM-CELLS
ISSN (print) / ISBN 0896-6273
e-ISSN 1097-4199
Zeitschrift Neuron
Quellenangaben Band: 68, Heft: 4, Seiten: 682-694 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed