Shake a leg



				Drumsticks delite! 25 MARCH 1999. Harvard Medical School researchers have finally taken sides in the struggle between lovers of chicken wings and drumsticks. In the process, they have opened a new career for birds that don't fly very well. Are you ready for the chicken as track star? That the discoveries now running through the field of limb development could also have practical significance is almost lost in the effort to imagine chickens with three legs and one lonely wing. This off-balance creature was designed and manufactured in the laboratory of Harvard geneticist Clifford Tabin. The research, published in the recent issue of Science, follows up on recent identifications at several labs of three genes that code for the differences between vertebrate forelimbs and hindlimbs. Two of these genes -- Pitx1 and Tbx4 -- were uniquely expressed, or operative, in legs. But which comes first, the chicken or the leg? More exactly, is Pitx1 or Tbx4 the driving force in leg development? Which gene starts the process by which a limb bud becomes a leg rather than a wing? To address this question, Tabin stuck Pitx1 into a virus, then squirted the virus into the region of a chick embryo where a wing would normally develop. The virus then inserted the gene into the embryonic cells. Doing the legwork And no, we are not making this up. The chickens developed with three legs and one wing. No, the third leg was not a perfect drumstick, probably because wing genes continued operating. Still, the "wrist" joint, which normally bends down on a chicken wing, was straight, as in a chicken leg. The feathers normally seen on a wing were absent, and the limb had rudimentary claws -- a sure sign of "legness." In a result sure to egg-cite the broiler industry, the musculature was characteristic of a leg rather than a wing. (A bird with quad drumsticks would carry significantly more meat than the traditional two-and-two layout.) Tabin couldn't take the time to talk with us, but we suspect the research did have purpose slightly more lofty than creating terrestrial chickens -- helping unravel the genetic sequence of limb development. The research showed that Pitx1 directed Tbx4, another "drumstick" gene, to operate. Where Pitx1 was absent, Tbx4 sat idle. Curiosity-lovers will be glad to learn that the story continues. A group of Japanese researchers is expected to publish shortly an even more effective transformation. They transported the control genes with electrical stimulation rather than a virus. The genes became active sooner, and the result apparently was chickens with wings at the bottom, and the legs up front. The Why Files is having a hard time envisioning that one. Would these birds fly upside down and run backwards? If so, they sound suspiciously like the military's long-sought all-terrain chicken. (If they can only add stealth capability, we might really have something...) On a slightly more serious note, researchers note that a rare human genetic condition, Holt-Oram syndrome, is associated with defects in the Tbx5 gene, which governs the shaping of fore-limbs -- what we call arms. Eventually, this highly impractical transformation could have a practical benefit. -- David Tenenbaum

				. Role of Pitx1 Upstream of Tbx4 in Specification of Hindlimb Identity, Malcolm Logan and Clifford Tabin, Science, March 12, 1999, pp. 1736-9. See also news article on pp. 1615-6.
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