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Starting over: Wnt reactivates dormant limb regeneration program

LA JOLLA, CA Chop off a salamander's leg and a brand new one will sprout in no time. But most animals have lost the ability to replace missing limbs. Now, a research team at the Salk Institute for Biological Studies has been able to regenerate a wing in a chick embryo a species not known to be able to regrow limbs - suggesting that the potential for such regeneration exists innately in all vertebrates, including humans.

Their study, published in the advance online edition of Genes and Development on Nov. 17, demonstrates that vertebrate regeneration is under the control of the powerful Wnt signaling system: Activating it overcomes the mysterious barrier to regeneration in animals like chicks that can't normally replace missing limbs while inactivating it in animals known to be able to regenerate their limbs (frogs, zebrafish, and salamanders) shuts down their ability to replace missing legs and tails.

"In this simple experiment, we removed part of the chick embryo's wing, activated Wnt signaling, and got the whole limb back - a beautiful and perfect wing," said the lead author, Juan Carlos Izpisa Belmonte, Ph.D., a professor in the Gene Expression Laboratory. "By changing the expression of a few genes, you can change the ability of a vertebrate to regenerate their limbs, rebuilding blood vessels, bone, muscles, and skin - everything that is needed."

This new discovery "opens up an entirely new area of research," Belmonte says. "Even though certain animals have lost their ability to regenerate limbs during evolution, conserved genetic machinery may still be present, and can be put to work again," he said. Previously, scientists believed that once stem cells turned into muscles, bone or any other type of cells, that was their fate for life and if those cells were injured, they didn't regenerate, but grew scar tissue.

Manipulating Wnt signaling in humans is, of course, not possible at this point, Belmonte says, but hopes that t
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Contact: Gina Kirchweger
kirchweger@salk.edu
858-453-4100 x1340
Salk Institute
17-Nov-2006


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