Monday, August 18, 2008

A Blueprint to Regenerate Limbs

Probing the salamander genome reveals clues to its remarkable ability to regrow damaged limbs and organs.

By Emily Singer

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Growing limbs: The axolotl salamander is one of the only vertebrates that can regrow entire limbs as an adult. Scientists are now sequencing parts of its unusually large genome in order to understand the genetic basis for this capability.
Credit: Jeramiah Smith

In its own way, the axolotl salamander is a mighty beast. Chop off its leg, and the gilled creature will grow a new one. Freeze part of its heart, and the organ will form anew. Carve out half of its brain, and six months later, another half will have sprouted in its place. "You can do anything to it except kill it, and it will regenerate," says Gerald Pao, a postdoctoral researcher at the Salk Institute for Biological Studies, in La Jolla, CA.

That extraordinary power of regeneration inspired Pao and his collaborator Wei Zhu, also at the Salk Institute, to probe the axolotl salamander's DNA. Despite decades of research on the salamander, little is known about its genome. That began to change last year, when Pao and his collaborators won one billion bases' worth of free sequencing from Roche Applied Science, based in Penzberg, Germany. Now that the data is in, scientists can finally begin the hunt for the genetic program that endows the animal with its unique capabilities.

While all animals can regenerate tissue to a certain extent--we can grow muscle, bone, and nerves, for example--salamanders and newts are the only vertebrates that can grow entire organs and replacement limbs as adults. When a leg is lost to injury, cells near the wound begin to dedifferentiate, losing the specialized characteristics that made them a muscle cell or bone cell. These cells then replicate and form a limb bud, or blastema, which goes on to grow a limb the same way that it forms during normal development.

Scientists have identified some of the molecular signals that play a key role in the process, but the genetic blueprint that underlies regeneration remains unknown. Researchers hope that by uncovering these molecular tricks, they can ultimately apply them to humans to regrow damaged heart or brain tissue, and maybe even grow new limbs.

In order to quickly identify sections of the salamander's genome involved in regeneration, the scientists sequenced genes that were most highly expressed during limb-bud formation and growth. They found that at least 10,000 genes were transcribed during regeneration. Approximately 9,000 of those seem to have related human versions, but there appear to be a few thousand more that don't resemble known genes. "We think many of them are genes that evolved uniquely in salamanders to help with this process," says Randal Voss, a biologist at the University of Kentucky, who is working on the project.

A Blueprint to Regenerate Limbs

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