Identifying the progeny of single neural stem cells in the adult murine forebrain

The process of the production of new neurons is called adult
neurogenesis. It occurs in specific regions in the adult mammalian
brain. The new neurons are being produced by so called adult neural
stem cells (aNSCs). Two niches that harbour these cells are the
subgranular zone (SGZ) of the dentate gyrus of the hippocampus and
the subependymal zone (SEZ) of the lateral ventricle. aNSCs in the
SEZ produce transit-amplifying progenitors (TAPs) which give rise
to neuroblasts (NBs) that migrate via the rostral migratory stream
(RMS) to the olfactory bulb (OB) where they mature to different
interneuron subtypes. The properties of the aNSCs in these regions
have been extensively investigated either by in vitro or in vivo
population studies. However, little is known about the behaviour of
an individual aNSC in the SEZ. In order to overcome this missing
knowledge, an analysis method was established in this thesis by
using double heterozygous mice for GLASTCreERT2 and R26R-Confetti.
This method allows the lineage tracing of aNSCs in the murine
brain. By titration of the dose of Tamoxifen that was injected
intraperitoneally into these mice, sparse labelling of individual
GLAST+ aNSCs was achieved. This method was then used to analyse the
behaviour of single aNSCs of the SEZ, as well as their progeny
(TAPs, NBs and neurons) over the course of time. These aNSCs are
able to produce a large progeny already within 3 and 7 days after
induction and show a drive towards neuronal maturation in between 3
and 8 weeks. The amplification step occurs at the level of the
progeny. This analysis at the single cell level showed insights
into the temporal and spatial profile of aNSCs. Compared to other
analyses performed at the population level, the progeny of aNSCs in
the SEZ reduces with time. It seems that the continuous
neurogenesis is maintained at the population level and therefore
reflects a population property. Furthermore, it was found that a
single aNSC is capable of producing multiple interneuron subtypes,
however the majority of cells produced are the deep granule
interneuron subtype.