Refined Spatial Manipulation of Neuronal Function by Combinatorial Restriction of Transgene Expression

Selective genetic manipulation of neuronal function in vivo requires techniques for targeting gene expression to specific cells. Existing systems accomplish this using the promoters of endogenous genes to drive expression of transgenes directly in cells of interest or, in “binary” systems, to drive...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2006-11, Vol.52 (3), p.425-436
Main Authors: Luan, Haojiang, Peabody, Nathan C., Vinson, Charles R., White, Benjamin H.
Format: Article
Language:English
Subjects:
Animals
Animals, Genetically Modified
beta-Galactosidase - genetics
beta-Galactosidase - metabolism
Cells, Cultured
DNA-Binding Proteins - physiology
Drosophila
Drosophila Proteins - metabolism
Gene expression
Gene Expression - physiology
Gene Expression Regulation
Genetic Vectors - genetics
Green Fluorescent Proteins - metabolism
Immunohistochemistry - methods
Insects
MOLNEURO
Neural networks
Neurons
Neurons - classification
Neurons - physiology
Rodents
Transcription factors
Transcription Factors - physiology
Transfection - methods
Transgenes
Values
Yeast
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Summary:Selective genetic manipulation of neuronal function in vivo requires techniques for targeting gene expression to specific cells. Existing systems accomplish this using the promoters of endogenous genes to drive expression of transgenes directly in cells of interest or, in “binary” systems, to drive expression of a transcription factor or recombinase that subsequently activates the expression of other transgenes. All such techniques are constrained by the limited specificity of the available promoters. We introduce here a combinatorial system in which the DNA-binding (DBD) and transcription-activation (AD) domains of a transcription factor are independently targeted using two different promoters. The domains heterodimerize to become transcriptionally competent and thus drive transgene expression only at the intersection of the expression patterns of the two promoters. We use this system to dissect a neuronal network in Drosophila by selectively targeting expression of the cell death gene reaper to subsets of neurons within the network.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2006.08.028