Open Access Highly Accessed Research article

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

Jingzhong Zhang1, Florian Giesert1, Karina Kloos1, Daniela M Vogt Weisenhorn125, Ludwig Aigner3, Wolfgang Wurst1245* and Sebastien Couillard-Despres3*

Author Affiliations

1 Institute of Developmental Genetics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Ingolstaedter Landstrasse 1, D-85764 Neuherberg, Germany

2 Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, D-80804 Munich, Germany

3 Institute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, Strubergasse 21, 5020 Salzburg, Austria

4 TUM, Technical University Munich, Chair of Developmental Genetics, c/o Ingolstaedter Landstrasse 1, D-85764 Neuherberg, Germany

5 DZNE, Deutsches Zentrum für Neurodegenerative Erkrankungen, Ludwig Maximilian University, c/o Adolf Butenandt-Institut für Biochemie, Schillerstraße 44, 80336 Munich, Germany

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BMC Neuroscience 2010, 11:158  doi:10.1186/1471-2202-11-158

Published: 31 December 2010

Abstract

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.