Cited by 1,876Neuroscience and Neuropharmacology ResearchAdvanced Fluorescence Microscopy TechniquesNeurogenesis and neuroplasticity mechanisms

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Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system

Livet, Jean, Weissman, Tamily A., Kang, Hyuno, Draft, Ryan W., Lu, Ju, Bennis, Robyn A., Sanes, Joshua R., Lichtman, Jeff W.·2007·Nature

DOI 10.1038/nature06293

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Abstract

Detailed analysis of neuronal network architecture requires the development of new methods. Here we present strategies to visualize synaptic circuits by genetically labelling neurons with multiple, distinct colours. In Brainbow transgenes, Cre/lox recombination is used to create a stochastic choice of expression between three or more fluorescent proteins (XFPs). Integration of tandem Brainbow copies in transgenic mice yielded combinatorial XFP expression, and thus many colours, thereby providing a way to distinguish adjacent neurons and visualize other cellular interactions. As a demonstration, we reconstructed hundreds of neighbouring axons and multiple synaptic contacts in one small volume of a cerebellar lobe exhibiting approximately 90 colours. The expression in some lines also allowed us to map glial territories and follow glial cells and neurons over time in vivo. The ability of the Brainbow system to label uniquely many individual cells within a population may facilitate the analysis of neuronal circuitry on a large scale.

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Authors: Livet, J., Weissman, T. A., Kang, H., Draft, R. W., Lu, J., Bennis, R. A., Sanes, J. R., & Lichtman, J. W.
Affiliations: Harvard University (US)
Corresponding author: Lichtman, Jeff W.
ORCID: Livet, Jean
Weissman, Tamily A.
Kang, Hyuno
Draft, Ryan W.
Lu, Ju
Sanes, Joshua R.
Lichtman, Jeff W.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2007-11
Volume: 450
Issue: 7166
Pages: 56-62
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature06293
OpenAlex: W2110232607
Cited by: 1,876
References: 42
Citations by year: 2026: 52 · 2025: 76 · 2024: 68 · 2023: 90 · 2022: 88 · 2021: 88 · 2020: 115 · 2019: 104 · 2018: 124 · 2017: 101 · 2016: 117 · 2015: 101 · 2014: 124 · 2013: 161 · 2012: 110
FWCI: 30.01
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords: Brainbow, transgenic mice, fluorescent proteins, Cre-loxP recombination, stochastic gene expression, neuronal circuit mapping, axon reconstruction, synaptic circuits, cerebellum, hippocampus
MeSH terms: Animals, Attachment Sites, Microbiological, Axons, Cell Communication, Cell Line, Cerebellum, Color, Genetic Engineering, Humans, Luminescent Proteins, Mice, Transgenic, Nervous System, Neural Pathways, Neuroglia, Recombination, Genetic, Stochastic Processes, Synapses, Time Factors, Gene Expression, Transgenes, Integrases, Mice

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Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system

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