Gene helps put stripes and blotches on cats of all sizes

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Researchers have discovered a specific gene that controls much of the development of the stripes, spots, and spots that are patterned on cat fur.

“Color patterns are one of those unsolved biological mysteries; there is no suitable model organism to study it – mice have no stripes or spots, ”says Gregory Barsh, Professor Emeritus of Genetics at Stanford University School of Medicine.

“The color patterns and variability seen in animals like tigers, cheetahs and zebras have raised some key questions for us: What are the developmental and cellular mechanisms that lead to these patterns, and how were they changed during the mammalian evolution? to create the amazing variety of shapes and forms that we see today? “

Barsh and his team answered part of this question: They identified a gene, DKK4, that helps regulate the early development of different coat patterns in domestic cats. DKK4, the team suggests, is likely to be involved in color patterns in all cats and perhaps other mammals as well.

The researchers’ results appear in Nature Communications. Barsh is the lead author. Researchers Christopher Kaelin and Kelly McGowan are co-lead authors.

A clue in the skin tissue

The researchers previously identified another gene that controls the variation in coat color in tabby cats. It’s the same gene that sets the difference between cheetahs and king cheetahs, which have thicker, more distinctive coat patterns.

“We knew from studying domestic cats that there were other genes that contribute to the formation of color patterns; we just didn’t know what they were, ”says Barsh.

They found a clue in the fetal cat tissue that seemed to guess the color of the coat: a thickening of the skin tissue in certain areas. These thickened regions form a “preliminary pattern” that mimics the possible color patterns in the fur of an adult cat. The thick area marks the later darker fur areas; the thin area marks the spots that are becoming lighter.

“We call this ‘establishment’ and it happens long before color appears and long before the hair follicles are mature,” says Barsh.

The preliminary sample provided the researchers with a kind of map that showed the cells involved in the pattern formation and the time at which the pattern was formed. The researchers then examined the genetic makeup of individual cells in the thick and thin regions of the skin. DKK4 was particularly active in the thickened skin, but not in the skin that remained relatively thin.

Abyssinian cats

But to really capture the connection between DKK4 and early pattern formation, the team turned to the Abyssinian cat. Abyssinians are known for having a fuzzy color in their fur, with tiny, darker markings squeezed together as if someone had used a pencil to lightly shade a gray layer on their orange-brown fur. Barsh and his team identified disruptive mutations in the DKK4 gene that are responsible for the apparent lack of tabby markings in the Abyssinian cat, an appearance known as “ticked”.

“If you remove DKK4, the dark areas won’t go away completely, but they’ll get smaller and denser,” says Barsh.

You may be wondering what about all-white cats? Or all black cats? They, too, are patterned under their single-colored stripes of fur. There are two different processes that create a color pattern: one that forms the pattern during embryonic development and one that translates the pattern into pigments that are produced in hair follicles. For monochromatic cats, the pattern is essentially overridden by instructions to create dark pigments throughout. The pigment is absent in white cats.

Cat fur patterns remain mysterious

Scientists don’t know exactly how DKK4 represents the color patterns of domestic cats, but they do know that DKK4 interacts with a class of proteins called WNTs, which are essential for early development. WNTs and DKK4 help form a pre-pattern when embryos are only two or three millimeters long, weeks before pigment is produced in the hair. DKK4 is involved in marking areas that will eventually have dark pigmented hair, says Barsh, but how those areas of skin remember their fate to induce the target pigment is unclear.

“This is one of the big unanswered questions in our work – how to combine the process of prepattern formation with the process that implements the pattern later in development,” he says. “That’s something we’re actively trying to figure out.”

Furthermore, DKK4 is only part of the answer to the mysterious genetics that dictate coat patterns. “There are other genes that are responsible, for example, why some cats have spots and why some cats have stripes,” says Barsh. Investigating this is also on their list.

The work was funded by the HudsonAlpha Institute for Biotechnology and the National Institutes of Health. Stanford’s genetics department also supported the work.

Source: Stanford University