Meis2 is a Pax6 co-factor in neurogenesis and dopaminergic periglomerular fate specification in the adult olfactory bulb

Zsuzsa Agoston, Peer Heine, Monika S. Brill, Britta Moyo Grebbin, Ann Christin Hau, Wiebke Kallenborn-Gerhardt, Jasmine Schramm, Magdalena Götz, Dorothea Schulte*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

68 Citations (Scopus)

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 proneurogenic 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 SVZOB system.

Original languageEnglish
Pages (from-to)28-38
Number of pages11
JournalDevelopment (Cambridge)
Volume141
Issue number1
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

Keywords

  • Adult neurogenesis
  • Mouse
  • Pax6
  • Subventricular zone
  • TALE-homeodomain proteins

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