Nature | Editorial

Deciphering the genes that give mammals their stripes and patterns

Researchers spot genes in an African mouse to identify the genetics of developmental patterning. 

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The Argentine writer Jorge Luis Borges tells the story of an Aztec priest, Tzinacán, imprisoned by the conquistador Pedro de Alvarado. In the cell next door is a jaguar: Tzinacán becomes convinced that the jaguar’s spots are not random blotches, but contain a message from his God that, could he decipher it, would offer a key to his escape. Any reader of Borges learns to appreciate his playful mash-up of fact and fiction. Of the small cast of characters in La Escritura de Dios (The God’s Script), de Alvarado was a real person, and Tzinacán probably an invention, although with Borges one can never be sure. Jaguars, though, definitely exist, and — like many mammals — have a pattern of spots that fascinates and tantalizes.

Understanding the origins of variegated colour patterns in mammalian fur is an abiding problem in biology. Other animals adopt a range of pigments, and even use optical effects such as iridescence to lend a chromatic gloss, yet the mammalian palette is mainly monochrome. A patch of skin either contains melanocytes, or it doesn’t.

This week, researchers report in Nature some progress on the problem with the African striped mouse, Rhabdomys pumilio (R. Mallarino et al. Nature; 2016). This creature has a stripe on either side of its spine, each a sandwich of light-coloured hair between two outriders of pure black. The rest of the mouse is an intermediate shade, except for a pale belly. The pattern starts to emerge long before a mouse is born.

The difference is down to gene expression. The white stripes are enriched in transcripts of Alx3, a transcription factor, which curbs the activities of a gene called Mitf. If left unhindered, this gene would allow melanocytes to differentiate and produce dark pigment.

As model organisms go, R. pumilio is very different from the laboratory mouse. Even further removed is the Eastern chipmunk, Tamias striatus. Chipmunks are more closely related to squirrels than to mice: the last common ancestor of mouse and chipmunk lived when dinosaurs did. Yet the formation of chipmunk stripes is governed by essentially the same processes that create the patterning in mouse skin, even though the mechanisms might have evolved independently in each case.

Study of the chipmunk shows other genes involved. Expression of one called Asip in lighter areas, another called Edn3 in darker, show that patterning is not down to a single genetic interaction. The work of Edn3 and other genes, we know, writes the script of spots and stripes in cats, from tabbies to cheetahs (C. B. Kaelin et al. Science 337, 1536–1541; 2012) — and so, presumably, in the coat of the jaguar that Tzinacán longed to decipher.

Much remains to be learnt. The stripes of mice and chipmunks don’t occur in the same places on the animal, and scientists still do not understand why the grass mouse Lemniscomys rosalia has only one stripe, whereas the ground squirrel Ictidomys tridecemlineatus has thirteen. The God’s script comes in many dialects.

“Oddities of skin pigmentation sometimes betoken deeper ailments.”

Skin pigmentation is superficial — literally — but the genes that create these patterns often have other, more profound purposes. The skin and hair of vertebrates derives from the neural crest, an embryonic tissue unique to vertebrates, which, migrating from the edge of the neural plate as it rolls up to create the spinal cord, interacts with tissues all over the body to create structures seen nowhere else in the kingdom of life. The neural crest sculpts not just hair, teeth and skin, but a long list of attributes, from the bones of the face to the nerves that line the intestines, parts of the heart and adrenal glands, and many crucial components of our sense organs. This is why oddities of skin pigmentation sometimes betoken deeper ailments. It explains why cats that are white are more than usually likely to be deaf.

So much is clear for Alx3. Mice deficient in this gene show a range of neural-tube closure defects, the incidence of which is reduced by folic acid (S. Lakhwani et al. Dev. Biol. 344, 869–880; 2010). This may explain why human mothers deficient in this vitamin run the risk of giving birth to babies with spina bifida. Again in humans, recessive mutations in ALX3 produce a series of facial malformations called fronto­rhiny, also related to failure of the facial bones to knit properly (S. R. F. Twigg et al. Am. J. Hum. Genet. 84, 698–705; 2009). The script runs deep, with many layers of meaning.

Did Tzinacán finally decipher the God’s script? The answer is yes: the jaguar’s fur encoded a spell which, if recited out loud, would make the prison vanish. But Tzinacán chose not to use it because, in the act of decipherment, he became a god himself.

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