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

Author

Listed:
  • Jean Livet

    (Harvard University, Cambridge, Massachusetts 02138, USA)

  • Tamily A. Weissman

    (Harvard University, Cambridge, Massachusetts 02138, USA)

  • Hyuno Kang

    (Harvard University, Cambridge, Massachusetts 02138, USA)

  • Ryan W. Draft

    (Harvard University, Cambridge, Massachusetts 02138, USA)

  • Ju Lu

    (Harvard University, Cambridge, Massachusetts 02138, USA)

  • Robyn A. Bennis

    (Harvard University, Cambridge, Massachusetts 02138, USA)

  • Joshua R. Sanes

    (Harvard University, Cambridge, Massachusetts 02138, USA)

  • Jeff W. Lichtman

    (Harvard University, Cambridge, Massachusetts 02138, USA)

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.

Suggested Citation

  • Jean Livet & Tamily A. Weissman & Hyuno Kang & Ryan W. Draft & Ju Lu & Robyn A. Bennis & Joshua R. Sanes & Jeff W. Lichtman, 2007. "Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system," Nature, Nature, vol. 450(7166), pages 56-62, November.
    • Handle: RePEc:nat:nature:v:450:y:2007:i:7166:d:10.1038_nature06293
    DOI: 10.1038/nature06293
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    Cited by:

    1. Marcus N. Leiwe & Satoshi Fujimoto & Toshikazu Baba & Daichi Moriyasu & Biswanath Saha & Richi Sakaguchi & Shigenori Inagaki & Takeshi Imai, 2024. "Automated neuronal reconstruction with super-multicolour Tetbow labelling and threshold-based clustering of colour hues," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Elle Koren & Alona Feldman & Marianna Yusupova & Avihay Kadosh & Egor Sedov & Roi Ankawa & Yahav Yosefzon & Waseem Nasser & Stefanie Gerstberger & Liam B. Kimel & Noa Priselac & Samara Brown & Sam Sha, 2022. "Thy1 marks a distinct population of slow-cycling stem cells in the mouse epidermis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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