The Fly Eyes Have It: A Second Master Gene?

In a startling experiment reported 2 years ago, Swiss biologists caused surplus eyes to sprout on fruit flies' wings, legs, and antennae--all by manipulating a single gene. Now researchers have found a second fruit fly gene that can duplicate this grotesque feat. The finding, reported in this month's issue of Development, suggests that two or more genes may act as a committee of "master controllers" that can order up complex organs by turning on other genes.

Developmental geneticist Graeme Mardon of Baylor College of Medicine in Houston discovered the eye-popping powers of the second gene, called dachshund (dac), by accident. Mardon found that the protein dac encodes resides in the cell nucleus, suggesting that the gene helps regulate the expression of other genes. But he couldn't find which genes those might be. Then in 1995, a team led by geneticist Walter Gehring of the University of Basel in Switzerland made the original dramatic discovery of the eyeless gene (ey). To trick the gene into becoming active where it should be dormant, Gehring's group had used genetically engineered fly larvae that produced a gene-activating protein called GAL4 in many different body parts, such as wings, legs, and antennae. Then they mated these flies to others in which ey was connected to a control switch activated by GAL4. The result was a brood of flies with eyes in unorthodox places.

Mardon, eager "to see what dac might be doing," borrowed the technique, linking not ey but dac to the GAL4-activated control switch. He and technician Weiping Shen found that 20% of the resulting flies developed clusters of fully formed fly eyes in odd locations. That's a much lower fraction than the Gehring team's 100%. But when Gehring's experiment was repeated in flies lacking dac, no weird eyes formed. This suggests to Mardon that the two genes evolved as partners, reinforcing each other's eye-building signals in a positive feedback loop. It's "a very interesting discovery," says Nancy Bonini, a Drosophila geneticist at the University of Pennsylvania.

So which is the true master-control gene for the fly eye? According to Mardon, neither. Gehring, however, maintains that ey is still the master. The bottom line, Mardon says, is that "it's really an oversimplification to say that any one gene is the master-control gene for eye development."

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