Researchers at Harvard Medical School (HMS) have identified a gene that is responsible for determining upper and lower limb development.
Their work showed that the gene, designated Pitxl, can partially transform the upper limb of a vertebrate into a structure resembling the lower limb.
Malcolm P. Logan, a research fellow in genetics at HMS, and Clifford J. Tabin, professor of genetics, performed experiments in which chickens developed wings with the characteristics of legs, such as leg-specific muscles and claws.
Pitxl, which is normally only active in the legs, was transferred to the developing wings of chicken embryos and is believed to be responsible for the observed deformities.
"This is the first time that a gene has been shown to direct a transformation of forelimb to hindlimb structures," Logan said in a press release.
Scientists have long been puzzled over how the forelimb and hindlimb develop, as the same genes for development are active in all four limb buds in the embryo. Logan and Tabin determined that additional wing- and leg-specific genes are involved in limb development.
"Up until a few years ago, we didn't understand how a limb was created," Tabin said.
The same gene causes the differentiation between thumbs and the other fingers, and between big and little toes. From this, Tabin and Logan deduced that one gene causes the differentiation of limbs into arms or legs.
The scientists chose to work with Pitxl because it is present during the early stages of the chicken embryo's development. Logan and Tabin believe that Pitxl activates other genes responsible for limb-specific development.
Now that Pitxl has been identified as a key regulator of limb formation, Logan said he wants to further examine the effects of this gene on embryo development.
"Now, we want to understand how these genes are actually interacting with the common cues which lead to the characteristic skeletal structure which form in the wing and the leg," Logan said.
In the future, Tabin also said he is interested in looking at the large-scale effects of these genes.
"We're interested in understanding the morphogenesis of the entire embryo," Tabin said, referring to the embryo's developmental stages. "In terms of Pitxl, I want to understand more what it does in limb patterning."
Although the study does not have any direct implications for the treatment of humans, Logan said the experiments would help scientists gain a better understanding of developmental disorders in the human embryo.
"I think that we're a long way off from correcting genetic problems," Logan said. "But, studying these genes will give us an idea of what's gone wrong when a gene has been damaged and why it causes certain diseases."
The findings of the Pitxl study will be published in the March 12 edition of Science.
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