Genes Determine Limb, Spine Development
Excerpt By Serena Gordon, Reuters Health

In a study appearing in the July 18 issue of Science, researchers from Utah report the discovery of specific genes that direct the development of the spine and limbs, and how slight variations in those genes tell the body how many ribs and other bones to create.

These genes, the researchers explain, are present in all creatures, but variations in them are the reason why some creatures have ribs that go from their neck to their tail, while humans have 12 pairs of ribs and lumbar and sacral vertebrae that form the lower spine.

"If you look at the mass amount of life around the world, we're all different. We have different bodies, but we're all using the same program, just slightly changed," says study author Mario Capecchi, who is co-chair of human genetics at the University of Utah Health Sciences Center and an investigator at the Howard Hughes Medical Institute in Salt Lake City.

"This is really a major piece of biology," says Gary Litman, director of molecular genetics at All Children's Hospital in St. Petersburg, Fla. "It explains why people aren't like snakes." Yet, he adds, this research emphasizes the remarkable genetic similarities between species.

For this study, the researchers studied the function of Hox genes, specifically Hox 10 and Hox 11. "Hox" is short for homeobox. Both vertebrate and invertebrate (spineless) creatures have Hox genes.

There are 13 different sets of Hox genes. Scientists already knew that Hox genes turn other genes on and off during the development from embryo to adult. During evolution, many Hox genes were duplicated, so some have redundant functions. That means if one gene is mutated, another that serves a redundant function can take over for the damaged gene and normal development can still take place.

Capecchi and his colleagues studied Hox genes in mice for the current research, though the results presumably apply to humans and other mammals.

When they "knocked out" all three of the Hox 10 genes in mice, the animals developed ribs all the way down to their tails. They also developed a very short thighbone and didn't develop kneecaps.

When they disabled all of the Hox 11 genes in the mice, the animals no longer formed sacral vertebrae. Sacral vertebrae are important because the pelvis attaches to them. The missing Hox 11 genes also caused malformation of the lower leg, with both the shin and calf bone developing improperly.

Capecchi says variations in these genes that give mammals shorter rib cages and a more flexible lower spine developed during evolution to give the animals more speed and agility on land.

He says by understanding the basic process of how mice and other life forms develop, future research can better target medications. He adds that by knowing which genes are responsible for limb development, doctors may be able to help children who are born with limb defects in the future.

He points out that humans, up until they are 2 years old, are already capable of very limited regeneration in the small bones of the finger. If an infant loses the top of a finger and the wound is not cauterized, according to Capecchi, the bone can regrow. And, he points out, other animals are capable of regeneration.

"The question is, can we ever do these kinds of things in humans?" he says, though he expects it will be many years before any clinical applications will come from this work.

"The direct applications of this type of research are enormous," Litman says. "It can set off whole new areas of research into skeletal defects."

More information

Visit the National Library of Medicine to learn more about genes. To learn more about genetics and genetic disorders, go to the National Human Genome Research Institute.

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