In vivo contribution of nestin- and GLAST-lineage cells to adult hippocampal neurogenesis

Nathan A. Decarolis, Maxwell Mechanic, David Petrik, Adam Carlton, Jessica L. Ables, Shveta Malhotra, Robert Bachoo, Magdalena Götz, Diane C. Lagace, Amelia J. Eisch

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Radial glia-like cells (RGCs) are the hypothesized source of adult hippocampal neurogenesis. However, the current model of hippocampal neurogenesis does not fully incorporate the in vivo heterogeneity of RGCs. In order to better understand the contribution of different RGC subtypes to adult hippocampal neurogenesis, we employed widely used transgenic lines (Nestin-CreERT2 and GLAST::CreERT2 mice) to explore how RGCs contribute to neurogenesis under basal conditions and after stimulation and depletion of neural progenitor cells. We first used these inducible fate-tracking transgenic lines to define the similarities and differences in the contribution of nestin- and GLAST-lineage cells to basal long-term hippocampal neurogenesis. We then explored the ability of nestin- and GLAST-lineage RGCs to contribute to neurogenesis after experimental manipulations that either ablate neurogenesis (i.c.v. application of the anti-mitotic AraC, cytosine-β-D-arabinofuranoside) or stimulate neurogenesis (wheel running). Interestingly, in both ablation and stimulation experiments, labeled RGCs in GLAST::CreERT2 mice appear to contribute to neurogenesis, whereas RGCs in Nestin-CreERT2 mice do not. Finally, using NestinGFP reporter mice, we expanded on previous research by showing that not all RGCs in the adult dentate gyrus subgranular zone express nestin, and therefore RGCs are antigenically heterogeneous. These findings are important for the field, as they allow appropriately conservative interpretation of existing and future data that emerge from these inducible transgenic lines. These findings also raise important questions about the differences between transgenic driver lines, the heterogeneity of RGCs, and the potential differences in progenitor cell behavior between transgenic lines. As these findings highlight the possible differences in the contribution of cells to long-term neurogenesis in vivo, they indicate that the current models of hippocampal neurogenesis should be modified to include RGC lineage heterogeneity.

Original languageEnglish (US)
Pages (from-to)708-719
Number of pages12
JournalHippocampus
Volume23
Issue number8
DOIs
StatePublished - Aug 1 2013

Keywords

  • Cre recombinase
  • Dentate gyrus
  • Genetic fate tracking
  • Radial glial cell
  • Subgranular zone

ASJC Scopus subject areas

  • Cognitive Neuroscience

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    Decarolis, N. A., Mechanic, M., Petrik, D., Carlton, A., Ables, J. L., Malhotra, S., Bachoo, R., Götz, M., Lagace, D. C., & Eisch, A. J. (2013). In vivo contribution of nestin- and GLAST-lineage cells to adult hippocampal neurogenesis. Hippocampus, 23(8), 708-719. https://doi.org/10.1002/hipo.22130