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PMID: 17088209 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Intramural

Refined spatial manipulation of neuronal function by combinatorial restriction of transgene expression.

Neuron ·Vol. 52 ·No. 3 ·2006-11-09 ·Pages 425-36

Luan H, Peabody NC, Vinson CR, White BH

Abstract

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.

MeSH Terms
Animals Animals, Genetically Modified Cells, Cultured DNA-Binding Proteins/physiology Drosophila Drosophila Proteins/metabolism Gene Expression/physiology Gene Expression Regulation Genetic Vectors/genetics Green Fluorescent Proteins/metabolism Immunohistochemistry/methods Neurons/classification,physiology Transcription Factors/physiology Transfection/methods Transgenes beta-Galactosidase/genetics,metabolism
Chemicals
DNA-Binding Proteins Drosophila Proteins Transcription Factors rpr protein, Drosophila Green Fluorescent Proteins beta-Galactosidase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Luan Haojiang
Laboratory of Molecular Biology, National Institute of Mental Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA.
Peabody Nathan C
Vinson Charles R
White Benjamin H
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Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
0896-6273
DOI
10.1016/j.neuron.2006.08.028
Published
2006-11-09
Pages
425-36
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC1713190
Subset
IM
Grants
NIMH NIH HHS · Z01 MH002800-03 · United States
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1016/j.neuron.2006.08.028 PMC Full Text View journal details
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