"Use it or lose it" might seem a fitting phrase for cave animals, who often lose their eyesight after many generations in perpetual darkness. But new research suggests that for some cave-dwelling fishes, blindness results from the careful coordination of gene expression, not simply from lack of use.
The teleost fish, Astyanax mexicanus, inhabits streams, lakes, and rivers of the southern United States, Mexico, and Central America. Most live a normal life in surface waters, but during the last 10,000 years, at least four populations of the fishes took up residence in limestone caves, and with their new digs, they acquired a new look. They lost their skin pigment and eyes, trading up for more taste buds and bigger jaws and teeth.
Scientists led by William Jeffery of the University of Maryland, College Park, had already uncovered clues about the genes involved. They had discovered that eyes begin to form in embryonic cave fish, but are killed later in development when the brakes are put on a gene known as pax6. Transplanting a lens from a surface-dwelling fish into a cave fish restored the eye, suggesting that eye development was regulated by gene activity in eye cells (Science, 28 July 2000, p. 631). But the scientists noticed that pax6 wasn't just turned down in the primordial eyes, it also was less active in the midline, the imaginary line dividing the left and right sides of a developing body. This hinted that genes that guide development might control blindness in the cave-dwelling fish.
To investigate, Jeffery and his colleagues Yoshiyuki Yamamoto and David Stock compared gene activity in cave-dwelling and surface fish. They found that while pax6 was turned down in the cave-dwellers' developing eyes, other genes were turned up, ones controlled by a management-level gene known as sonic hedgehog that's active in the midline. When they injected extra sonic hedgehog into surface-dwelling embryos, the fish ended up with smaller retinas and almost no lens. And when they injected a chemical that inhibits hedgehog's activity into cave fish embryos, the fish had 30% more lens than normal, the researchers report in the 13 October issue of Nature. The finding suggests that sonic hedgehog prevents eye formation by dialing down pax6 and perhaps revving up other genes.
When a body part is no longer needed, scientists usually assume that mutations accumulate in the genes controlling the structure, eventually preventing it from working or being made. "That was the dogma," says Stephen Ekker of the University of Minnesota, Twin Cities. But because the cave fish eyes are actively killed, natural selection is probably doing its thing, says Jeffery. And that, he adds, might come as a surprise even to Darwin, who thought the cave fishes' loss of sight might be an exception to the rules of natural selection. The next step, of course, will be to figure out what the fish gain by losing their sight.