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DeCarolis, N.A.* ; Mechanic, M.* ; Petrik, D.* ; Carlton, A.* ; Ables, J.L.* ; Malhotra, S.* ; Bachoo, R.* ; Götz, M. ; Lagacen, D.C.* ; Eisch, A.J.*

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

Hippocampus 23, 708-719 (2013)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter subgranular zone; dentate gyrus; genetic fate tracking; radial glial cell; Cre recombinase; Neural Stem-cells ; Central-nervous-system ; Dentate Gyrus ; Progenitor Cells ; Analysis Reveals ; Radial Glia ; Precursor Cells ; Mouse ; Fate ; Astrocytes
ISSN (print) / ISBN 1050-9631
e-ISSN 1098-1063
Zeitschrift Hippocampus
Quellenangaben Band: 23, Heft: 8, Seiten: 708-719 Artikelnummer: , Supplement: ,
Verlag Wiley
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Stem Cell Research (ISF)