The colors of the Brainbow: when science looks like art

In a previous post I wrote that science was not art. Well, it’s true, science is not art but sometimes it looks a lot like art. Sometimes it produces images that wouldn’t be out of place among the displays of an art gallery. Like the images of the Brainbow mice.

Image of the Brainbow mouse from the Cell Picture Show

Beautiful, isn’t it? But what is it, you’re asking. Mouse neurons. Not from any mouse though. Sorry to disappoint you, mouse neurons don’t naturally look like that. These neurons are from a Brainbow mouse, a type of mouse engineered by scientists so its neurons are labeled with different colors.

Genes have promoters, DNA sequences that tell cells if they should express the genes or not. Some genes are expressed by most cells while others are only expressed by a specific type of cell, and this information is given by the promoter. By expressing a green fluorescent protein from a jellyfish under the control of other genes promoters, researchers have been able to study where these genes are expressed in an organism. Fused to another protein, the green fluorescent protein gives insight into where this protein is localized in the cell. Scientists have enlarged the color palette with mutant proteins engineered to fluoresce other colors than green so they could analyze the localization of one protein compared to another. Or, as in the Brainbow mouse, to distinguish one cell from another.

Except there’s an extra trick in the Brainbow mouse. For the Brainbow mouse two DNA sequences are inserted in the mouse genome: one is made up of a promoter that drives expression in neurons and four genes of differently colored fluorescent proteins, the other contains a promoter and the gene of the Cre recombinase protein. Between the genes of the colored proteins are specific DNA sequences called loxP sites. The Cre recombinase recognizes loxP sites and triggers the breaking and joining of two identical sites with the result that the piece of DNA in between is cut. Pairs of identical loxP sites are placed between the genes so that there are three possible arrangements (see picture Basic Genetic Construct). Each arrangement has a different gene following the promoter and, as only the gene directly after the promoter is expressed, each arrangement produces a protein of a different color. Which arrangement the Cre recombinase produces is random so it can be different from one neuron to the next.

The four genes of differently colored fluorescent proteins separated by different loxP sites and their three possible arrangements. Image credit: Lawson Kurtz et al./Duke University via Wikipedia

What’s more is that several copies of the DNA sequence with the genes of the colored proteins are inserted in the mouse genome. As the Cre recombinase acts at random on any of the pair of loxP sites, the arrangement from one copy can be different from another. So one neuron can not only express different colored proteins from its neighbor but also in different quantities (see picture Building Brainbow). And that’s how the neurons of the Brainbow mouse can be of about 90 different colors. A bit like the pixels of a screen which are of different colors through the combination of different intensities of red, green and blue.

The combination of different quantities of different colors produces the colors of the Brainbow. Image credit: Lawson Kurtz et al./Duke University via Wikipedia

The Brainbow mouse wasn’t created simply for the beauty of the images it produces. It was thought as a tool to better understand the brain. With about 75 million neurons the architecture of the mouse brain is complex and twisted. If you can paint neurons about 90 different colors, you can get a better picture of their connections and study how they change during development or after an injury. And if it looks like art, it’s a plus.

Livet et al. Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. (2007) Nature 450(7166): pp. 56-62

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3 comments

  1. BL

    Amazing neuroscience is amazing 🙂

  2. Pingback: Playing God: GloFish® fluorescent fish FAQ « turcanin. cu ţ.

  3. Pingback: iLabs: The Answer to Brainbows and Their Colors | NC Museum of Natural Sciences Education Blog

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