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The transcription factor Pax6 regulates survival of dopaminergic olfactory bulb neurons via crystallin αA.
Neuron 68, 682-694 (2010)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
B-CRYSTALLIN; ADULT NEUROGENESIS; MAMMALIAN TELENCEPHALON; PARKINSONS-DISEASE; CEREBRAL-CORTEX; GENETIC-CONTROL; KNOCKOUT MICE; PAIRED DOMAIN; MUS-MUSCULUS; STEM-CELLS
Language
english
Publication Year
2010
HGF-reported in Year
2010
ISSN (print) / ISBN
0896-6273
e-ISSN
1097-4199
Journal
Neuron
Quellenangaben
Volume: 68,
Issue: 4,
Pages: 682-694
Publisher
Cell Press
Publishing Place
Cambridge, Mass.
Reviewing status
Peer reviewed
POF-Topic(s)
30204 - Cell Programming and Repair
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s)
Stem Cell and Neuroscience
Genetics and Epidemiology
Genetics and Epidemiology
PSP Element(s)
G-500800-001
G-500700-002
G-550900-001
G-500700-002
G-550900-001
PubMed ID
21092858
Scopus ID
78449311026
Erfassungsdatum
2010-11-30