Neuronal fate determinants of adult olfactory bulb neurogenesis.
Adult neurogenesis in mammals is restricted to two small regions, including the olfactory bulb, where GABAergic and dopaminergic interneurons are newly generated throughout the entire lifespan. However, the mechanisms directing them towards a specific neuronal phenotype are not yet understood. Here, we demonstrate the dual role of the transcription factor Pax6 in generating neuronal progenitors and also in directing them towards a dopaminergic periglomerular phenotype in adult mice. We present further evidence that dopaminergic periglomerular neurons originate in a distinct niche, the rostral migratory stream, and are fewer derived from precursors in the zone lining the ventricle. This regionalization of the adult precursor cells is further supported by the restricted expression of the transcription factor Olig2, which specifies transit-amplifying precursor fate and opposes the neurogenic role of Pax6. Together, these data explain both extrinsic and intrinsic mechanisms controlling neuronal identity in adult neurogenesis.
Hack
Michael A
MA
GSF-National Research Center for Environment and Health, Institute for Stem Cell Research, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany.
Saghatelyan
Armen
A
de Chevigny
Antoine
A
Pfeifer
Alexander
A
Ashery-Padan
Ruth
R
Lledo
Pierre-Marie
PM
Götz
Magdalena
M
D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins; D002455:Cell Division / Q000502:physiology; D002460:Cell Line / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D004805:Ependyma / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000166:cytology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010641:Phenotype; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology; D013234:Stem Cells / Q000166:cytology; D014018:Tissue Distribution
D051792:Basic Helix-Loop-Helix Proteins; D004298:Dopamine; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; C512773:Olig2 protein, mouse; C000605732:Pax6 protein, mouse