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The study explains how the cat got their stripes

Cats come in a variety of sizes with a range of varying fur colors and patterns. Understanding the basis of a cat’s color pattern is a longstanding interest for developmental and evolutionary biology.

It is well known that hair follicle cells are the source of the black, brown, yellow, and red pigments that color hair or fur. Although, where this process of establishing the color pattern takes place remains unclear.

Genes controlling simple color variation, like albinism or melanism, are the same in all mammals for the most part. However, the biology underlying mammalian color patterns have long been a mystery.

Now, scientists at the HudsonAlpha Institute for Biotechnology identified molecules that regulate the establishment of coat color patterns in tabby cats.

For the study, scientists collected fetal tissue that would have otherwise been discarded during spay procedures. After studying the fetal cat skin tissue, they found stripe-like alterations in epidermal (skin) thickness early in fetal development.

The patterns of epidermal thickness resembled tabby fur patterns in adult animals.

Kelly McGowan, MD, Ph.D., said, “Our findings from the morphological studies suggest that even before melanocytes enter the epidermis, the cells are predestined to signal for specific fur color. By understanding the developmental window and cell type in which color pattern establishment occurs, we were able to dive deeper and discover the molecules involved in pattern development.”

Scientists performed single-cell gene expression analysis on fetal cat skin cells before the thick and thin patches became apparent. This analysis determined that epidermal expression of a gene called Dickkopf 4 (Dkk4) marks areas of fetal skin that give rise to hair follicles that later produce dark pigment. Dkk4 is an inhibitor of Wnt signaling, which helps determine cell fates and spurs cell growth during development in many animals.

A Dkk4 mutation
(a) A Dkk4 mutation in the kitten without the necklace causes dark tabby markings to become smaller and more numerous. (b) An Abyssinian cat with a Dkk4 mutation that is associated with an apparent absence of tabby markings. (c) A close-up view of the Abyssinian coat suggests that microscopic dark markings may be present (Photo credit for c, Martin Bahmann CC BY-SA 3.0)

Further experiments also showed that Dkk4 is linked to other color patterns in cats. In the Abyssinian cat, the apparent absence of dark tabby markings, a trait referred to as “Ticked,” accentuates the alternating color bands present on individual hairs. The team discovered that all Ticked cats carry loss-of-function mutations in Dkk4.

HudsonAlpha senior scientist Chris Kaelin, Ph.D., said, “Our analysis identifies a network of molecules involved in pattern formation. Several of the molecules, including Dkk4, are known to function coordinately as activators and inhibitors, exactly as Alan Turing predicted 70 years ago.”

Greg Barsh, MD, Ph.D., HudsonAlpha Faculty Investigator, Faculty Chair, and Smith Family Chair in Genomics said, “In Abyssinian cats with the Ticked phenotype, the consensus has been that there is an absence of the dark tabby markings. Based on our new findings, we propose that instead, the typical tabby markings have increased in number and decreased in size to the extent that they are just not readily apparent.”

Journal Reference:
  1. Kaelin, C.B., McGowan, K.A. & Barsh, G.S. Developmental genetics of color pattern establishment in cats. Nat Commun 12, 5127 (2021). DOI: 10.1038/s41467-021-25348-2

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