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New gene helps understanding of limbs and digits
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by Rachel Patzer
Friday, September 13, 2002
Researchers could be one step closer to preventing mutations in human development.
Scientists at the University of Wisconsin-Madison, in collaboration with Vanderbilt University, have discovered that two genes, rather than one, are instrumental in the development of limbs and digits in mice.
Previously, the Sonic the Hedgehog gene (Shh) was thought to be the main gene responsible for forming fingers, toes and limbs.
This new research, published in Nature magazine, found that another gene, known as Gli3, is also fundamental in forming limbs and digits in mice. Professor of anatomy John Fallon and graduate student Randy Dahn conducted the research on the UW campus.
“All indications are that studies in mice and chicken are directly related to understanding these malformations in humans,” Fallon said.
A new understanding of the significance of the Gli3 gene could take scientists a step closer to identifying the causes of human limb and digit mutations, such as the development of more than five fingers.
In the experiment, Fallon and Dahn genetically altered mice in several different ways. One group had only the Shh gene and another only the Gli3 gene. The researchers studied how the limbs and digits developed in each group and found that both Shh and Gli3 need to be present for the formation of normal limbs and digits.
One of the most common human mutations, polydactyly — the formation of more than five digits — is caused by an absence of one of these genes.
Fallon and Dahn state that the Shh and Gli3 genes also play important roles in normal development of human tissues of the brain, spinal cord, eyes, gut, genitalia, lungs, and even hair.
“While it is simply not possible or responsible to currently consider genetic manipulation of human embryos, our findings may be applicable to understanding how regeneration of human digits might be accomplished,” Dahn said.
Shh and Gli3 may also tie into the evolutionary shift that took place 340 million years ago. When one of these two genes is removed from mice, scientists can recreate an animal that closely resembles one from that time period. Somewhere along the evolutionary path, the combination of these genes must have evolved into present-day mice. Armed with this information, the researchers are currently looking at other genes that may work with Shh and Gli3 in hopes that future discoveries in limb and digit development will continue. “I hope that scientists’ better understanding of the causes of common birth defects will lead to future discoveries,” said Beth Theusch, a UW-Madison sophomore majoring in genetics.
