Have you ever wondered how your palm became different from the back of your hand? Scientists now think they have a clue to the answer: They have found the genes in chickens that tell cells whether they lie on the front or on the back of a developing limb.
Researchers have known for several years that when fruit fly larvae metamorphose into adults, a gene called fringe produces a protein that tells certain cells to become the wing margin, the leading edge of a developing wing. In separate studies reported in today's issue of Nature, a team led by geneticist Juan Carlos Ispisúa Belmonte at the Salk Institute in La Jolla, California, and another led by geneticist Cliff Tabin at Harvard Medical School found a very similar gene in chicks, named Radical fringe (R-fng), that is active on one side of a budding chick wing. The gene isn't active on the other side of the wing, they found, because Engrailed-1, another gene first found in flies, suppresses it.
Both groups report that a strand of rapidly dividing cells on the tip of the growing vertebrate limb, called the apical ectodermal ridge (AER), arises exactly on the border between cells that switch on R-fng and those that don't. The researchers tested this observation by infecting chick embryos with viruses carrying R-fng, causing the gene to be expressed in many different places. They found that the chicks formed AERs and sprouted limbs wherever there was a boundary between cells that expressed the transplanted R-fng genes and cells that weren't infected. This jumbled pattern of development confirms that this boundary creates the AER. Another gene then steps in, the researchers found, to specify which side of the AER will become dorsal (the exterior of the wing). That gene, called Wnt-7a, is also suppressed by Engrailed-1, so it is active on only one side of the AER, and that side becomes the dorsal side, the researchers found.
"The wing margin in flies and the AER in chicks seem to be equivalent structures," says Belmonte. "But obviously, the fly wing and the vertebrate arm are so different that somewhere you have to start finding differences, and we have found the first: Engrailed controls Radical fringe in chicks, which it doesn't do in flies."
"Both of these studies are very exciting," says developmental geneticist Lee Niswander of Columbia University. "We're seeing more and more often now that [fruit flies] and vertebrates use the same signaling pathways over and over again in many stages of development. Somehow, these molecules have evolved to work together in many different situations."