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In 2007, the labs of Professors Jeff Lichtman and Josh Sanes introduced a multicolor labeling strategy called “Brainbow.”

It involves use of transgenic mice in which various combinations of fluorescent proteins are expressed in neurons, with each neuron making its own choice from a palette of some 100 colors. It thus results in the indelible marking of mouse neurons with multiple, distinct colors. This method simplifies the arduous job of following neuronal axons and dendrites through a complicated neuropil.  It has also been adapted for use in flies and fish, and applied to analysis of lineage in many non-neuronal tissues of mice.

As experience accumulated, however, it became apparent that the initial lines, called Brainbow 1 and 2, were not as useful as the investigators had hoped for its intended purpose.

Accordingly, Dawen Cai, a postdoctoral fellow in the Lichtman and Sanes labs, took on the challenging task of improving the method. Aided by two research assistants. Kim Cohen and Tuan Luo, he generated new lines of mice that overcome limitations of the initial lines, such as insufficient brightness and poor color balance.  He also extended the method adapting it for use with viral vectors, which can be delivered at particular times or in particular regions of the brain.

Their new paper, published in Nature Methods, describes the improvements and, equally important, makes the new transgenic lines, plasmids, and viruses freely available to investigators who can now use them – and perhaps come up with ideas for further improvements and applications.

Read more in nature methods

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