How does a cat get its stripes? A biological puzzle is solved

Folklore is full of stories about the coat patterns of cats: How the tiger got its stripes. How the leopard got its spots. And scientists ask the same questions, although not necessarily about large predators. The research may focus instead on something like the mackerel tabby pattern in domestic shorthairs.

The question of how cat stripes and splotches are made touches on some of the deepest theoretical puzzles of biology. How does a blob of cells organise itself into a fruit fly, or a panda? What tells the bones in a limb to become a hand, or paw, or the ribbing of a leathery wing? What tells some skin cells to grow dark hair and others lighter hair?

A team of geneticists reported in the journal Nature Communications that it had identified a gene in domestic cats that plays a key role in creating the traditional tabby stripe pattern, and that the pattern is evident in embryonic tissue even before hair follicles start to grow.

The inheritance of cat coats - how to breed for this or that pattern - is well known. But how patterns emerge in a growing embryo "really has been an unsolved mystery," said Gregory Barsh, an author of the new report. "We think this is really the first glimpse into what the molecules might be" that are involved in the process, he added. The research team included Barsh, Christopher Kaelin and Kelly McGowan, all affiliated with the HudsonAlpha Institute for Biotechnology in Alabama and the Stanford University School of Medicine.

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"It's a very beautiful study," said Hopi Hoekstra, an evolutionary biologist at Harvard University, who has collaborated with Barsh but was not part of this research. "It advances our understanding of one of the most fundamental questions in developmental biology: How do patterns form?" Hoekstra said.

Barsh said the theoretical basis of the team's work dated back to a groundbreaking paper by Alan Turing, famous for his work in computer science and code breaking. Turing's genius was not limited to computers, however. He wrote a paper called "The Chemical Basis of Morphogenesis" in 1952 that "really laid the groundwork for the entire field of mathematical biology," Barsh said.

The paper describes what is called a reaction diffusion process in which two chemicals, one that stimulates gene activity and one that inhibits it, can result in regular, alternating patterns. Researchers who study the development of coat patterns have thought this process could produce stripes in cat coats; Barsh said the team’s research had confirmed this hypothesis.

Further, he said, the study shows for the first time that the gene Dkk4 and the protein it produces are central to the process. Dkk4 is the inhibitor in the process. The research depended on a collaboration with programmes that trap feral cats, spay or castrate them, and release them in order to reduce overpopulation and improve the health of feral cats. Many female cats that are spayed in these programs are pregnant. The embryos, at too early a growth stage to be viable, are usually discarded. For this study, the researchers collected the embryonic tissue and brought it to the lab.

From more than 200 prenatal litters, McGowan looked for patterns in the tissue at the different stages of growth in the embryos. She found a pattern of what she described as thick and thin areas of tissue in the top layer of the embryonic skin, never before reported. The regions, she said, “mimic what’s going on in the adult cat pigmentation patterns.” The same patterns that will appear in an adult cat’s coat as stripes or blotches appear first in the embryo before there is any hair or even hair follicles.

Cats are a fantastic model - easier to study than zebras or leopards - that have developed a dazzling array of spots, stripes and everything in between.

The team then looked for genes that might be active at that period in early embryonic growth. When Kaelin looked at the tissue that showed the thick and thin tissue pattern that was the precursor of stripes, he said, “the one molecule that stood out from the rest was this Dkk4.” The full name of the protein and the gene is Dickkopf 4: The name is German for “thick head,” a characteristic the gene produced in frogs.

There were different amounts of Dkk4 in the thick and the thin tissue areas. The Dkk4 protein was inhibiting the genes that produce other signalling molecules known as Wnt proteins, Barsh said. Even more telling, when there was a mutation in the Dkk4 gene, the stripes became thinner, to the point that a plain pattern called Ticked emerged.

The authors emphasise that the patterns they investigated are only a “fraction of the pattern diversity that exists among domestic cat breeds.” In the future, Barsh said, one target for the team will be to uncover how the tissue pattern translates to colour when hair follicles grow. Hoekstra said the work highlighted the value of domestic animals to science. “Cats are a fantastic model - easier to study than zebras or leopards - that have developed a dazzling array of spots, stripes and everything in between.” – New York Times