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  3. Medizin - Open Access LMU - Teil 17/22 Podcast
  4. A powerful transgenic tool for fate mapping and functional analysis of newly generated neurons
Background: Lack of appropriate tools and techniques to study fate
and functional integration of newly generated neurons has so far
hindered understanding of neurogenesis' relevance under
physiological and pathological conditions. Current analyses are
either dependent on mitotic labeling, for example
BrdU-incorporation or retroviral infection, or on the detection of
transient immature neuronal markers. Here, we report a transgenic
mouse model (DCX CreERT2) for time-resolved fate analysis of newly
generated neurons. This model is based on the expression of a
tamoxifen-inducible Cre recombinase under the control of a
doublecortin (DCX) promoter, which is specific for immature
neuronal cells in the CNS. Results: In the DCX-CreERT2 transgenic
mice, expression of CreERT2 was restricted to DCX+ cells. In the
CNS of transgenic embryos and adult DCX-CreERT2 mice, tamoxifen
administration caused the transient translocation of CreERT2 to the
nucleus, allowing for the recombination of loxP-flanked sequences.
In our system, tamoxifen administration at E14.5 resulted in
reporter gene activation throughout the developing CNS of
transgenic embryos. In the adult CNS, neurogenic regions were the
primary sites of tamoxifen-induced reporter gene activation. In
addition, reporter expression could also be detected outside of
neurogenic regions in cells physiologically expressing DCX (e. g.
piriform cortex, corpus callosum, hypothalamus). Four weeks after
recombination, the vast majority of reporter-expressing cells were
found to co-express NeuN, revealing the neuronal fate of DCX+ cells
upon maturation. Conclusions: This first validation demonstrates
that our new DCX-CreERT2 transgenic mouse model constitutes a
powerful tool to investigate neurogenesis, migration and their
long-term fate of neuronal precursors. Moreover, it allows for a
targeted activation or deletion of specific genes in neuronal
precursors and will thereby contribute to unravel the molecular
mechanisms controlling neurogenesis.

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„A powerful transgenic tool for fate mapping and functional analysis of newly generated neurons“

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