New gene clearly resolves an eye debate.

In Greek myth, the Cyclopes were a race of fierce giants equipped with a single eye in the middle of their foreheads. It's a sad reality that a similar affliction, a single eye or the fusion of two eyes, strikes human fetuses and that this rare condition is invariably accompanied by fatal developmental abnormalities.

Both legend and fact pose a provocative question for developmental biologists: Does a normal pair of eyes originate from two independent regions in an embryo, or must a single precursor area split in two? In the Feb. 1 Development, researchers reporting on the embryonic activity of a new gene called ET choose the latter answer.

Yi Rao and his research group at Washington University School of Medicine in St. Louis found ET during a search for the transcription factors involved in the embryogenesis of the frog Xenopus laevis. Transcription factors are DNA-binding proteins that control gene activity.

Rao's group discovered that ET is active in two regions of the embryo, one a stretch of tissue that develops into a secretory gland and another that forms the retinas of the eyes. More important, the biologists noticed that the ET-active retinal area emerges early in frog development as a single band of tissue and later splits into two distinct regions.

Further experiments in chick embryos and with another eye development gene called Pax-6 buttressed the argument that vertebrate eyes start as a single patch. Finally, the scientists determined that a nearby piece of the embryo, the prechordal mesoderm, induces the single region to split.

"The middle of this region gets turned off, or suppressed, from eye formation," says Rao, noting that when the prechordal mesoderm is removed from a developing chick or frog embryo, a single eye forms.

Although early embryologists did not have the powerful tools of genetics, they often deduced the same answers that today's scientists can obtain more definitively, observes Robert M. Grainger, who studies eye development at the University of Virginia in Charlottesville. By the 1930s, embryologists had already put together a strong case that the eyes stem from a single embryonic area, he argues.

"A lot of biologists have used new techniques to revisit old problems. What Rao has done is to bring to [this problem] some technology that makes the answer much clearer. There's no doubt about that," says Grainger.