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

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2010 Nov 25

PMID 21092858

Citations 55

Authors

Jovica Ninkovic

Luisa Pinto

Stefania Petricca

Alexandra Lepier

Jian Sun

Michael A Rieger

Timm Schroeder

Ales Cvekl

Jack Favor

Magdalena Gotz

Affiliations

Soon will be listed here.

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.

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