title: Long-Term Fate Mapping Using Conditional Lentiviral Vectors Reveals a Continuous Contribution of Radial Glia-Like Cells to Adult Hippocampal Neurogenesis in Mice.
abstract: Newborn neurons are generated throughout life in two neurogenic regions, the subventricular zone and the hippocampal dentate gyrus. Stimulation of adult neurogenesis is considered as an attractive endogenous repair mechanism to treat different neurological disorders. Although tremendous progress has been made in our understanding of adult hippocampal neurogenesis, important questions remain unanswered, regarding the identity and the behavior of neural stem cells in the dentate gyrus. We previously showed that conditional Cre-Flex lentiviral vectors can be used to label neural stem cells in the subventricular zone and to track the migration of their progeny with non-invasive bioluminescence imaging. Here, we applied these Cre-Flex lentiviral vectors to study neurogenesis in the dentate gyrus with bioluminescence imaging and histological techniques. Stereotactic injection of the Cre-Flex vectors into the dentate gyrus of transgenic Nestin-Cre mice resulted in specific labeling of the nestin-positive neural stem cells. The labeled cell population could be detected with bioluminescence imaging until 9 months post injection, but no significant increase in the number of labeled cells over time was observed with this imaging technique. Nevertheless, the specific labeling of the nestin-positive neural stem cells, combined with histological analysis at different time points, allowed detailed analysis of their neurogenic potential. This long-term fate mapping revealed that a stable pool of labeled nestin-positive neural stem cells continuously contributes to the generation of newborn neurons in the mouse brain until 9 months post injection. In conclusion, the Cre-Flex technology is a valuable tool to address remaining questions regarding neural stem cell identity and behavior in the dentate gyrus.
authors.affiliation: Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Flanders, Belgium.
authors.forename: Sarah-Ann
authors.initials: SA
authors.lastname: Aelvoet
authors.affiliation: Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Flanders, Belgium.
authors.forename: Jesus
authors.initials: J
authors.lastname: Pascual-Brazo
authors.affiliation: Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Flanders, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Libbrecht
authors.affiliation: Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Flanders, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Reumers
authors.affiliation: Leuven Viral Vector Core, KU Leuven, Leuven, Flanders, Belgium.
authors.forename: Rik
authors.initials: R
authors.lastname: Gijsbers
authors.affiliation: Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Flanders, Belgium.|Leuven Viral Vector Core, KU Leuven, Leuven, Flanders, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Van den Haute
authors.affiliation: Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Flanders, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Baekelandt
mesh_terms: D000818:Animals; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics*; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D064231:Nestin / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism
chemical_list: D064231:Nestin