Temporal control of retroviral transgene expression in newborn cells in the adult brain.
Neural stem/progenitor cells (NSPCs) generate new neurons throughout life in distinct areas of the adult mammalian brain. Besides classical transgenesis-based approaches, retrovirus-mediated genetic manipulation is frequently used to study mechanisms that regulate neurogenesis in the nervous system. Here, we show that fusion of a tamoxifen-regulatable estrogen receptor (ER(T2)) motif to transcription factors (i.e., ASCL1 and NEUROD1) enables temporal control of transgene expression in adult mouse NSPCs in vitro and in vivo. Thus, the approach described here represents a versatile strategy for regulating gene expression to study gene function in dividing cells and their progeny.
Brain Research Institute, Faculty of Medicine, University of Zurich, 8057 Zurich, Switzerland ; Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland ; Neuroscience Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland.
Simon M G
SM
Braun
Raquel A C
RA
Machado
Sebastian
S
Jessberger
D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000166:cytology*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000821:virology; D055495:Neurogenesis; D011960:Receptors, Estrogen / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics*; D019076:Transgenes
D051792:Basic Helix-Loop-Helix Proteins; D011960:Receptors, Estrogen; C065500:ASCL1 protein, human; C093970:NEUROD1 protein, human