Technicolor zebrafish reveal how skin heals

March 21, 2016, Duke University
To the naked eye, a Skinbow zebrafish has a magenta tone. Credit: Chen-Hui Chen, Duke University

Scientists can now watch how hundreds of individual cells work together to maintain and regenerate skin tissue, thanks to a genetically engineered line of technicolor zebrafish.

Every cell on the surface of the fish, from the center of the eye to the tip of each scale, is genetically programmed to glow with a slightly different hue. But these zebrafish weren't bred to brighten up an aquarium; the colors effectively stamp each cell with a permanent barcode, letting scientists track its movements in a live animal for days or even weeks at a time.

"Before we can fully understand , we need to be able to monitor what are doing," said Kenneth D. Poss, James B. Duke Professor of Cell Biology at Duke University and lead scientist on the team that designed the color-coding system. "This is a cutting-edge way to visualize hundreds or thousands of cells at once in a regenerating tissue."

The system, which the researchers call Skinbow, is described March 21 in the journal Developmental Cell.

Skinbow's cells derive their technicolor hues from a technology called Brainbow, originally created to label individual neurons in the brain with distinct colors. Skin cells in the Skinbow zebrafish randomly express different combinations of red, green and blue fluorescent proteins, resulting in over 70 hues that can be reliably distinguished under a microscope. These colors are only expressed in the outermost layer of , and remain permanent throughout each cell's lifetime.

Every cell on the surface of this genetically engineered zebrafish expresses a unique combination of green, red and blue fluorescent proteins, resulting in over 70 different hues that can be distinguished under a microscope. Credit: Chen-Hui Chen, Duke University
"It is like you have given each cell an individual barcode," said Chen-Hui Chen, a postdoctoral fellow in Poss's lab and lead author on the study. "You can precisely see how individual cells collectively behave during regeneration."

The team also designed software to track individual cells in a series of images collected over time, allowing them to compile full "biographies" of many different cells at once.

This video shows a three-dimensional view of Skinbow-labeled fin epithelium, four days after fin amputation. The surface epithelial cells are labeled in multi-color using Skinbow. Dividing basal cells under the surface are shown in green. Credit: Chen et al./Developmental Cell 2016

Using this system, the researchers followed movements and changes in shape and size of hundreds of individual skin cells over three weeks of normal skin turnover. They also monitored the behaviors of skin cells after different types of injury, from minor exfoliation to complete amputation of a fin.

The experiments revealed a surprising diversity in cellular responses to injury. For example, following fin amputation, pre-existing cells were initially recruited from below the amputation plane to cover the wound. Then, new cells were generated at a rapid pace, and finally some cells at the tip of the regrown tissue temporarily grew in size to provide surface coverage.

Technicolor zebrafish reveal how skin heals
A color-coding technique called Skinbow affects the outermost layer of skin cells throughout this fish's body. Here, the multicolor cells are evident on the exposed portion of a dissected scale. Credit: Chen-Hui Chen, Duke University
"These are quite different cellular mechanisms, and one would not be able to detect the sequence or the appearance of these mechanisms without being able to track all or most of the on the surface of the fin," Poss said.

In the future, the researchers hope to combine 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.

"This is a very powerful system to see how regeneration happens," Poss said.

Explore further: Just a few cell clones can make heart muscle

More information: "Multicolor Cell Barcoding for Long-Term Surveillance of Epithelial Regeneration in Zebrafish," Chen-Hui Chen, Alberto Puliafito, Ben D. Cox, Luca Primo, Yi Fang, Stefano Di Talia and Kenneth D. Poss. Developmental Cell, online March 21, 2016. DOI: 10.1016/j.devcel.2016.02.017

Related Stories

Just a few cell clones can make heart muscle

April 25, 2012
Just a handful of cells in the embryo are all that's needed to form the outer layer of pumping heart muscle in an adult zebrafish.

Study uncovers foundations of heart regeneration

May 4, 2015
While the human heart can't heal itself, the zebrafish heart can easily replace cells lost by damage or disease. Now, researchers have discovered properties of a mysterious outer layer of the heart known as the epicardium ...

To grow or not to grow: A step forward in adult vertebrate tissue regeneration

March 27, 2014
The reason why some animals can regenerate tissues after severe organ loss or amputation while others, such as humans, cannot renew some structures has always intrigued scientists.

Scientist identifies mechanism to regenerate heart tissue

March 9, 2016
The MDI Biological Laboratory has announced new discoveries about the mechanisms underlying the regeneration of heart tissue by Assistant Professor Voot P. Yin, Ph.D., which raise hope that drugs can be identified to help ...

Recommended for you

Female biology – two X chromosomes and ovaries – extends life and protects mice from aging

December 18, 2018
Around the world, women outlive men. This is true in sickness and in health, in war and in peace, even during severe epidemics and famine. In most animal species, females live longer than males.

Get a warrant: Researchers demand better DNA protections

December 18, 2018
New laws are required to control access to medical genetic data by law enforcement agencies, an analysis by University of Queensland researchers has found.

Wound care revolution: Put away your rulers and reach for your phone

December 18, 2018
Monitoring a wound is critical, especially in diabetic patients, whose lack of sensation due to nerve damage can lead to infection of a lesion and, ultimately, amputation. Clinicians and healthcare professionals at the McGill ...

Using light to stop itch

December 17, 2018
Itch is easily one of the most annoying sensations. For chronic skin diseases like eczema, it's a major symptom. Although it gives temporary relief, scratching only makes things worse because it can cause skin damage, additional ...

Law professor suggests a way to validate and integrate deep learning medical systems

December 13, 2018
University of Michigan professor W. Nicholson Price, who also has affiliations with Harvard Law School and the University of Copenhagen Faculty of Law, suggests in a Focus piece published in Science Translational Medicine, ...

Exercise-induced hormone irisin triggers bone remodeling in mice

December 13, 2018
Exercise has been touted to build bone mass, but exactly how it actually accomplishes this is a matter of debate. Now, researchers show that an exercise-induced hormone activates cells that are critical for bone remodeling ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.