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Neuron
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License: Elsevier Non-Commercial
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The Transcription Factor Pax6 Regulates Survival of Dopaminergic Olfactory Bulb Neurons via Crystallin αA

Authors: Ales Cvekl; Jian Sun; Stefania Petricca; Jack Favor; Michael A. Rieger; Alexandra Lepier; Jovica Ninkovic; +4 Authors

The Transcription Factor Pax6 Regulates Survival of Dopaminergic Olfactory Bulb Neurons via Crystallin αA

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.

Country
Germany
Keywords

Homeodomain Proteins, Male, Neurons, B-CRYSTALLIN; ADULT NEUROGENESIS; MAMMALIAN TELENCEPHALON; PARKINSONS-DISEASE; CEREBRAL-CORTEX; GENETIC-CONTROL; KNOCKOUT MICE; PAIRED DOMAIN; MUS-MUSCULUS; STEM-CELLS, PAX6 Transcription Factor, Cell Survival, Neuroscience(all), Dopamine, Mice, Transgenic, Crystallins, Olfactory Bulb, Mice, Inbred C57BL, Repressor Proteins, Mice, Cell Line, Tumor, Animals, Paired Box Transcription Factors, Eye Proteins

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Powered by OpenAIRE graph
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
100
Top 10%
Top 10%
Top 10%
hybrid