title: 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.
authors.affiliation: Helmholtz Zentrum München, Institute of Stem Cell Research, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany.
authors.forename: Jovica
authors.initials: J
authors.lastname: Ninkovic
authors.forename: Luisa
authors.initials: L
authors.lastname: Pinto
authors.forename: Stefania
authors.initials: S
authors.lastname: Petricca
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lepier
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rieger
authors.forename: Timm
authors.initials: T
authors.lastname: Schroeder
authors.forename: Ales
authors.initials: A
authors.lastname: Cvekl
authors.forename: Jack
authors.initials: J
authors.lastname: Favor
authors.forename: Magdalena
authors.initials: M
authors.lastname: Götz
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D003459:Crystallins / Q000235:genetics / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C511246:CRYAA protein, human; D003459:Crystallins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D004298:Dopamine