title: Generation of GABAergic and dopaminergic interneurons from endogenous embryonic olfactory bulb precursor cells.
abstract: During the embryonic period, many olfactory bulb (OB) interneurons arise in the lateral ganglionic eminence (LGE) from precursor cells expressing Dlx2, Gsh2 and Er81 transcription factors. Whether GABAergic and dopaminergic interneurons are also generated within the embryonic OB has not been studied thoroughly. In contrast to abundant Dlx2 and Gsh2 expression in ganglionic eminences (GE), Dlx2 and Gsh2 proteins are not expressed in the E12.5-13.5 mouse OB, whereas the telencephalic pallial domain marker Pax6 is abundant. We found GABAergic and dopaminergic neurons originating from dividing precursor cells in E13.5 OB and in short-term dissociated cultures prepared from the rostral half of E13.5 OB. In OB cultures, 22% of neurons were GAD+, of which 53% were Dlx2+, whereas none expressed Gsh2. By contrast, 70% of GAD+ cells in GE cultures were Dlx2+ and 16% expressed Gsh2. In E13.5 OB slices transplanted with EGFP-labeled E13.5 OB precursor cells, 31.7% of EGFP+ cells differentiated to GABAergic neurons. OB and LGE precursors transplanted into early postnatal OB migrated and differentiated in distinct patterns. Transplanted OB precursors gave rise to interneurons with dendritic spines in close proximity to synaptophysin-positive boutons. Interneurons were also abundant in differentiating OB neural stem cell cultures; the neurons responded to the neurotrophin Bdnf and expressed presynaptic proteins. In vivo, the Bdnf receptor TrkB colocalized with synaptic proteins at the glomeruli. These findings suggest that, in addition to receiving interneurons from the LGE, the embryonic OB contains molecularly distinct local precursor cells that generate mature GABAergic and dopaminergic neurons.
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Vergaño-Vera
authors.forename: María J
authors.initials: MJ
authors.lastname: Yusta-Boyo
authors.forename: Fernando
authors.initials: F
authors.lastname: de Castro
authors.forename: Antonio
authors.initials: A
authors.lastname: Bernad
authors.forename: Flora
authors.initials: F
authors.lastname: de Pablo
authors.forename: Carlos
authors.initials: C
authors.lastname: Vicario-Abejón
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002454:Cell Differentiation; D017690:Cell Transplantation; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D018398:Homeodomain Proteins / Q000378:metabolism; D007395:Interneurons / Q000166:cytology / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009830:Olfactory Bulb / Q000737:chemistry / Q000166:cytology / Q000196:embryology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D011247:Pregnancy; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; C088334:Distal-less homeobox proteins; D005136:Eye Proteins; C109498:Gsh2 protein, mouse; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D005680:gamma-Aminobutyric Acid; D004298:Dopamine