Boston, MA--March 8, 1999--The structural differences between an arm and a leg are crucial to their proper function: digits that flex and curl are needed in a hand for grasping while strong muscles in the legs allow for walking and running. Now researchers at Harvard Medical School have unveiled the molecular instructions that command these differences, and have identified a gene that can partially transform the upper limb of a vertebrate into a structure that resembles its lower limb. Their findings, published in the March 12 Science, open new doors to understanding how vertebrate limbs acquire their identity. Postdoctoral fellow Malcolm Logan and Clifford Tabin, professor of genetics at Harvard Medical School, took a gene that is normally only active in legs and transferred it to the forming wings of chick embryos. The resulting structures lost many of their wing characteristics and gained those of a leg: feathers were gone, claws appeared at the end on the digits, and leg-specific muscles were clearly identifiable.
"This is the first time that a gene has been shown to direct a transformation of forelimb (arm or wing) to hindlimb (leg) structures," said Logan, principal author of the study.
The gene, called Pitx1, is one of three genes thought to play a role in giving
upper and lower extremities their identity, and the first one whose function has
been confirmed. The other two, Tbx4 and Tbx5, are members of the same gene
family and are active only in the leg or in the wing, respectively.
Scientists had long speculated that genes like these would be needed to set up
forelimb and hindlimb structural differences. However, as researchers began to
isolate genes involved in guiding the growth and development of limbs, it became
obvious that the crucial signals for limb patterning were present in all four
"limb buds"--the outgrowths on the sides of an embryo's trunk that represent the
beginnings of the future limbs. If the same signals supervise the dev
Contact: Peta Gillyatt
Harvard Medical School