title: Pax6 is required for making specific subpopulations of granule and periglomerular neurons in the olfactory bulb.
abstract: The subventricular zone (SVZ) produces different subclasses of olfactory bulb (OB) interneurons throughout life. Little is known about the molecular mechanisms controlling the production of different types of interneurons. Here we show that most proliferating adult SVZ progenitors express the transcription factor Pax6, but only a small subpopulation of migrating neuroblasts and new OB interneurons derived from these progenitors retains Pax6 expression. To elucidate the cell-autonomous role of Pax6 in OB neurogenesis, we transplanted green fluorescent protein-expressing embryonic forebrain progenitors of the dorsal lateral ganglionic eminence from Pax6 mutant Small Eye (Pax6(Sey/Sey)) mice into the SVZ of adult wild-type mice. Pax6(Sey/Sey) progenitors produce neuroblasts capable of migrating into the OB but fail to generate dopaminergic periglomerular and superficial granule cells. Interestingly, superficial granule neurons also express mRNA for tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Our data show that SVZ neuroblasts are heterogeneous and that Pax6 is required in a cell-autonomous manner for the production of cells in the dopaminergic lineage.
authors.affiliation: Department of Neurological Surgery, Program in Developmental and Stem Cell Biology, University of California, San Francisco, California 94143, USA.
authors.forename: Minoree
authors.initials: M
authors.lastname: Kohwi
authors.forename: Noriko
authors.initials: N
authors.lastname: Osumi
authors.forename: John L R
authors.initials: JL
authors.lastname: Rubenstein
authors.forename: Arturo
authors.initials: A
authors.lastname: Alvarez-Buylla
mesh_terms: D000818:Animals; D016380:Brain Tissue Transplantation; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D016332:Fetal Tissue Transplantation; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D007395:Interneurons / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009830:Olfactory Bulb / Q000166:cytology* / Q000502:physiology*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine