A genetically engineered fish with skin cells in all the colors of the rainbow has provided researchers with a unique opportunity to track how individual cells move as skin regrows.
Every cell on the surface of the fish is genetically programmed to glow with a slightly different hue. The idea is that the colors give each cell what researchers refer to as a permanent barcode, allowing them to effectively see how individual cells collectively behave during regeneration - a task normally made difficult by the fact that individual skin cells look so similar to each other.
This technicolor zebrafish, aptly named "Skinbow," was created using a gene that randomly codes for red, blue and green fluorescent proteins, resulting in more than 70 hues that can accurately be distinguished under a microscope. This gene was then injected into single-cell fish embryos.
"Before we can fully understand tissue regeneration, we need to be able to monitor what individual cells are doing," explained Kenneth D. Poss, a professor of cell biology at Duke University. "This is a cutting-edge way to visualize hundreds or thousands of cells at once in a regenerating tissue."
Researchers led by Chen-Hui Chen, a postdoctoral fellow in Poss's lab, designed software that allows them to monitor individual cells in a series of images collected over time. Using this, researchers tracked the movements and changes in shape and size of hundreds of individual skin cells over three weeks of normal skin regeneration. They also monitored the behaviors of skin cells after experiencing different types of injury, ranging from minor exfoliation to complete amputation of a fin.
Overall, researchers found a surprising amount of diversity in cellular responses to injury. After fin amputation, for example, skin cells in the surrounding area raced to the injury site and doubled in size to cover the wound. Deeper down, a sheet of new skin cells was generated at a rapid pace to provide surface coverage.
"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 cells on the surface of the fin," Poss said.
In future studies researchers hope to paint a more complete picture of skin tissue regeneration by combining the Skinbow technology with other imaging techniques. Their findings, in turn, 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 concluded.
Their findings were recently published in the journal Developmental Cell.
