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In vivo contribution of nestin‐ and GLAST‐lineage cells to adult hippocampal neurogenesis
Author(s) -
DeCarolis Nathan A.,
Mechanic Maxwell,
Petrik David,
Carlton Adam,
Ables Jessica L.,
Malhotra Shveta,
Bachoo Robert,
Götz Magdalena,
Lagace Diane C.,
Eisch Amelia J.
Publication year - 2013
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.22130
Subject(s) - neurogenesis , nestin , hippocampal formation , dentate gyrus , neuroscience , biology , neural stem cell , subgranular zone , progenitor cell , genetically modified mouse , stem cell , transgene , microbiology and biotechnology , subventricular zone , genetics , gene
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‐CreER T2 and GLAST::CreER T2 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::CreER T2 mice appear to contribute to neurogenesis, whereas RGCs in Nestin‐CreER T2 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. © 2013 Wiley Periodicals, Inc.