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Timing can take the stripes off a zebrafish

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In the video clip, a 10-day-old zebrafish gets its stripes in this series of images taken one a day for 30 days. (Video Credit: D Parichy Lab/UW. Image credit: "zebrafish" via Shutterstock)

New research offers insights into how zebrafish get their stripes, as well as how to “erase” them.

The findings give new understanding about genes and cell behaviors that underlie pigment patterns in zebrafish that, in turn, could help unravel the workings of pigment cells in humans and other animals, skin disorders such as melanoma, and cell regeneration.

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“Using zebrafish as a model, we’re at the point where we have a lot of the basic mechanisms, the basic phenomenology of what’s going on, so we can start to look at some of these other species that have really different patterns and start to understand them,” says David Parichy, a professor of biology at University of Washington and corresponding author of both papers.

Zebrafish, a tropical freshwater fish about 1.5 inches long, belongs to the minnow family and is a popular addition to home aquariums. Adults have long horizontal blue stripes on their sides, hence the reference to “zebra.”

These patterns have roles in schooling, mate-selection, and avoiding predators. Given their importance, scientists have long wanted to know where these pigment cells come from and how they make stripes and other arrangements.

Unlike humans with a single pigment cell type—the amount of melanin that produces color being determined by everyone’s individual genetics—there are three pigment cells that make the zebrafish pattern.

Researchers have previously shown that all three types of pigment cells communicate with one another to organize zebrafish stripes and that two of the pigment cells—one that creates black and another silver—come from stem cells.

Stripes in the making

In Science, two papers report that the cells called xanthophores that produce the color orange don’t come from stem cells as had long been assumed. Instead, they come from pre-existing cells in the embryo.

The researchers also determined the surprising process by which this occurs: cells in the embryo first mature into xanthophores and then, when it’s time to make stripes, these same cells lose their color, increase in number, and then turn back into xanthophores with color.

“This is remarkable because cells do not normally lose their mature properties, let alone regain them later,” Parichy says. “Knowing how xanthophores achieve this feat could provide clues to regeneration of tissues and organs without the need for stem cells.”

Even more remarkably, the authors found that the re-development of orange-producing xanthophores requires thyroid hormone, the same hormone that turns tadpoles into frogs, suggesting that xanthophores undergo their own metamorphosis. At the same time thyroid hormone blocks development of the black cells, setting the proper shade overall.

“In the last 10 to 15 years people trying to understand these patterns have concentrated on how the three pigment cell types interact with each other. We showed the tremendous dependence on thyroid hormone for the pattern that develops,” Parichy says.

Timing takes stripes away

In the Nature Communications paper, Parichy’s group reports on a gene that drives the unusually early appearance of xanthophores—independent of thyroid hormone—in another species, the pearl danio. Unlike zebrafish this species lacks stripes: its pigment cells are intermingled and arranged uniformly on the body, giving it a pearly orange color.

By expressing this gene the same way in zebrafish, the researchers caused the fish to make extra-early xanthophores and the fish produced a uniform pattern like the pearl danio instead of their usual stripes.

“Really simple changes in timing make totally different patterns,” Parichy says.

This unexpected result shows that a core network of interacting cells can generate very different patterns in response to changes in timing, a discovery that could explain color pattern evolution across a variety of species.

“If you’d asked me five years ago if we’re in a position to have some useful hypotheses about where patterns come from in other species, I’d have said, ‘no,'” Parichy says.

“But I think now we’re really at the point where we understand a lot of the basics and we can start to frame testable hypotheses. We can see how much of this is just a simple difference in timing, a difference in thyroid hormone responsiveness, or a difference in cellular communication itself.”

Additional researchers contributed from University of Washington, Iowa State University, and University of Oregon. The NIH funded both studies.

Source: University of Washington

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