New System Depicts Skin Regeneration in Technicolor

Thanks to a genetically engineered line of technicolor zebrafish, researchers can now visualize skin regeneration at high resolution in real time.

Many available methods rely on samples that are "snapshots" of cell growth and movement, but the new system, called Skinbow, can illustrate how hundreds of individual cells work together to maintain and regenerate skin tissue.

In the future, the Skinbow system with other imaging techniques to paint a more complete picture of skin tissue regeneration. It could also be applied to study how other biological stressors, such as drugs, infection or cancer, impact the cellular mechanisms underlying tissue healing. 

The research team genetically engineered a line of zebrafish that expressed red, green, and blue fluorescent proteins in different combinations on the uppermost layer of skin cells--even in the epithelium covering the eye. This skinbow line results in hundreds of potential colors for any given cell to display. At least 70 to 80 of these colors can be reliably distinguished from one another, the researchers report.

The cellular color-coding shows up when the zebrafish are imaged with a microscope under red, green, and blue channels and the images are combined, though the animals have a reddish tint to the naked eye.

The researchers examined the zebrafish under normal conditions, then subjected the study animals to a variety of injuries--ranging from mild alterations like skin exfoliation with a dry tissue to more severe injuries such as fin amputation--to watch how the cells responded. For example, after a zebrafish's fin was amputated, the team observed the following sequence during fin regeneration: first, skin cells rapidly migrated from nearby areas to cover the injury site; second, new epithelial cells were produced to supplement the recruited cells; and third, the cells expanded in size to cover more space at the wound.

The findings appear in the March 21, 2016 issue of Developmental Cell.

PHOTO CAPTION: This image shows a dissected zebrafish scale. Surface epithelial cells tagged with Skinbow cover the top half of the scale.

Credit: Chen et al./Developmental Cell