title: Meis2 is a Pax6 co-factor in neurogenesis and dopaminergic periglomerular fate specification in the adult olfactory bulb.
abstract: Meis homeodomain transcription factors control cell proliferation, cell fate specification and differentiation in development and disease. Previous studies have largely focused on Meis contribution to the development of non-neuronal tissues. By contrast, Meis function in the brain is not well understood. Here, we provide evidence for a dual role of the Meis family protein Meis2 in adult olfactory bulb (OB) neurogenesis. Meis2 is strongly expressed in neuroblasts of the subventricular zone (SVZ) and rostral migratory stream (RMS) and in some of the OB interneurons that are continuously replaced during adult life. Targeted manipulations with retroviral vectors expressing function-blocking forms or with small interfering RNAs demonstrated that Meis activity is cell-autonomously required for the acquisition of a general neuronal fate by SVZ-derived progenitors in vivo and in vitro. Additionally, Meis2 activity in the RMS is important for the generation of dopaminergic periglomerular neurons in the OB. Chromatin immunoprecipitation identified doublecortin and tyrosine hydroxylase as direct Meis targets in newly generated neurons and the OB, respectively. Furthermore, biochemical analyses revealed a previously unrecognized complex of Meis2 with Pax6 and Dlx2, two transcription factors involved in OB neurogenesis. The full pro-neurogenic activity of Pax6 in SVZ derived neural stem and progenitor cells requires the presence of Meis. Collectively, these results show that Meis2 cooperates with Pax6 in generic neurogenesis and dopaminergic fate specification in the adult SVZ-OB system.
authors.affiliation: Institute of Neurology (Edinger Institute), J. W. Goethe University Medical School, D-60528 Frankfurt, Germany.
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Agoston
authors.forename: Peer
authors.initials: P
authors.lastname: Heine
authors.forename: Monika S
authors.initials: MS
authors.lastname: Brill
authors.forename: Britta Moyo
authors.initials: BM
authors.lastname: Grebbin
authors.forename: Ann-Christin
authors.initials: AC
authors.lastname: Hau
authors.forename: Wiebke
authors.initials: W
authors.lastname: Kallenborn-Gerhardt
authors.forename: Jasmine
authors.initials: J
authors.lastname: Schramm
authors.forename: Magdalena
authors.initials: M
authors.lastname: Götz
authors.forename: Dorothea
authors.initials: D
authors.lastname: Schulte
mesh_terms: D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D005136:Eye Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D058953:Neural Stem Cells / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: C088334:Distal-less homeobox proteins; D000089622:Doublecortin Domain Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D008869:Microtubule-Associated Proteins; C102641:Mrg1 protein, mouse; D009479:Neuropeptides; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase
keywords: Adult neurogenesis; Mouse; Pax6; Subventricular zone; TALE-homeodomain proteins