How Cats Got Their Stripes: The Mystery Of Mammalian Color Patterns

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Iin the years 1902 Just stories, Rudyard Kipling explained how the leopard got its spots in what would today be considered an extremely racist fable. Now Christopher Kaelin, Kelly McGowan and Gregory Barsh, of the HudsonAlpha Institute of Biotechnology, discovered how the tabby cat got its stripes: from a signal in the fetus. Their findings appear in Nature Communication.

“The genes that control simple color variation, like albinism or melanism, are mostly the same in all mammals. However, the biology underlying the mammalian color model has long been a mystery, a mystery we have now gained new insight from using domestic cats, ”said Barsh, editor-in-chief of PLoS Genetics.

To trace the origins of the common striped coat pattern, the team analyzed gene expression in single skin cells of fetuses taken from feral cats as part of trap sterilization programs – half of those females are pregnant. The work revealed a new mechanism behind the origin of the scratches, like that of Jackie in the photograph.

Alan Turing’s idea

Color is easier to study in fish, where individual pigment cells designate a specific color and the organization of cells forms patterns. It’s a bit like following the instructions on a paint-by-number kit and watching an image emerge as small areas of color come together.

In mammals, the situation is more complex. Local-acting hormones determine the production of pigments from cells called melanocytes, but the number of melanocytes tends to be the same in all individuals of a species. Humans with different skin colors have roughly the same number of melanocytes, but cells produce different amounts of the two variations of melanin pigment. The overall color reflects the proportions of brown-black eumelanin and red-yellow pheomelanin.

The colors of cats are more complex than the hues of humanity, with light and dark streaks and spots creating the distinctive coat patterns of ocelots, jaguars, cheetahs and, of course, the legendary leopard spots. These are called periodic color patterns. A hypothesis explaining how this complex coloring can occur dates from the early 1950s from a seemingly unlikely source – Alain turing of computer fame.

Alain Turing. Credit history

Also a theoretical biologist, Turing argued that patterns such as the coat colors of big cats could come from molecules that turn on and off as they move through the tissues of a developing body at different speeds. . Its “reaction-diffusion mechanism” envisioned activating and inhibiting molecules supervising the deposition of pigments before birth by creating patterns of coat colors. An activator staining a cell triggers an inhibitor which diffuses and suppresses the deposition of pigment in neighboring cells. Jackie’s stripes were born from this molecular tango.

How a signal sets the stage for scratches

A hair follicle is born from the stem cells, which divide and are pushed upward as they specialize, accumulating keratin proteins and melanin pigments. In a fetal cat, a follicle is developed to give rise to a light or dark coat, called a “pattern element identity”. Then a bath of local hormonal signals fixes the color hair by hair.

The color stamp persists even if the constituent cells split, and that way the stripe pattern on a kitten remains in the cat it becomes. An adult cheetah has the same number of spots as a young one. Just like that, a dark hair falls out and is replaced by a new dark hair. If I could replicate this process, I wouldn’t need to have my hair dyed periodically as some strands are bleached more blonde than others to create an overall effect. Cats don’t need to go to the vet for a touch-up of highlights to maintain their scratches.

Credit: Laura Alonso / Elaine Fuchs

The researchers looked for the molecules behind the cat scratches.

“Even before melanocytes enter the epidermis, cells are predestined to signal a specific fur color. By understanding the window of development and the cell type in which the establishment of the color patterns occurs, we were able to delve deeper and discover the molecules involved in the development of the patterns, ”said McGowan.

The details

The researchers analyzed the messenger RNAs produced in the individual follicle cells of fetal cats. This commonly used technique, called single-cell RNA-seq, identifies the collection of mRNA in an isolated cell at a selected anatomical location and physiological time, which indicates, protein by protein, what is happening. (I described RNA-seq in a COVID context recently here)

The RNA is isolated (1), purified (2), sequenced (3), then analyzed (4). Credit: AllGenetics

In the “gene expression pre-model” that the experiments revealed, the team discovered a strong signal from a well-studied gene in many vertebrates called Dickkopf 4 (“Thick head” in German). In humans, the protein encoded by the gene inhibits liver cancer.

The first idea of ​​the upcoming feline phenotype is a pattern of raised stripes along the single cell layer which is the epidermis as a cat embryo hovers on the verge of becoming a fetus, roughly the equivalent of a human embryo at the end of 7 weeks. The two types of melanin will be deposited in the furrows, the first rough forms of stripes. It’s a bit like adding lines of chocolate to the vanilla batter of a developing marble cake before swirling.

Experiments have shown that the expression of 277 genes differs between fetal epidermal cells intended to be dark and light, but the most influential is Dickkopf 4. Over the days, Dickkopf 4 stimulates the deposition of dark pigment in some cells of the developing hair shaft. The gene encodes a protein that inhibits the signaling of another protein called Wnt, which helps define the fate of cells during prenatal growth and development.

A clue in Abyssinian cats

Geneticists like to create mutants to reveal and describe the normal function of a gene. This is why I worked with flies whose legs came out of the head and out of the mouth.

When Dickkopf 4 is mutant, the result is a cat with a ‘ticked off’ pattern – a uniform color of sand or dull brown which, on a closer look, consists of hairs that are neither dark nor light, but which have colored bands. This phenomenon is common in mammals and is called agouti. Torn from a feline, an agouti hair would be white at the ends and grayish in the middle. A little yellow on the hair gives it a shine, so a cat preening in the spotty sun may appear to have a different pattern if viewed from a different angle. It’s like the oily glop I put on my hair.

Two ticked cats are the familiar Abyssinian (aka an agouti tabby) and the exotic and domesticated wild cat the servaline (savannah motif), which sells for around $ 20,000.

Abyssinian cat. Credit: ASPCA

Barsh explains. “In Abyssinian cats with the ticked phenotype, the consensus was that there are no dark tabby markings. Based on our new findings, we propose that instead, typical tabby marks have increased in number and decreased in size to the extent that they are simply not evident.

Mutations that mask tabby stripes in Abyssinians abolish the function of the gene. “Loss of function” has been a standard term in genetics for decades; it was not invented to describe the nefarious research on COVID.

To summarize Kaelin, “Our analysis identifies a network of molecules involved in pattern formation. Several of the molecules work in a coordinated fashion as activators and inhibitors, just as Alan Turing predicted 70 years ago.

Ricki Lewis has a doctorate in genetics and is a science writer and author of several books on human genetics. She is an Assistant Professor at the Alden March Bioethics Institute at Albany Medical College. Follow her to her website or Twitter @rickilewis

A version of this article originally appeared on PLOS and has been republished here with permission. PLOS can be found on Twitter @PLOS

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