Scientists regenerate a wing in chick embryo

Washington, Nov. 18 : Researchers at the Salk Institute for Biological Studies have successfully regenerated a wing in a chick embryo, a species not known to be able to regrow limbs.

Their experiment suggests that the potential for such regeneration exists innately in all vertebrates, including humans.

The study published in the online edition of Genes and Development demonstrates that vertebrate regeneration is under the control of the powerful Wnt signalling system.

Lead author Dr. Juan Carlos Izpisza Belmonte, a professor in the Gene Expression Laboratory, says that once activated, Wnt signalling system overcomes the mysterious barrier to regeneration in animals like chicks that cannot normally replace missing limbs. But when inactivated, it can shut the ability to regenrate limbs even in the animals known for this quality of theirs.

"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," he said.

"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," he added.

Belmonte believes that many animals that had lost their ability to regenerate limbs during evolution might have conserved the genetic machinery, exploiting which this quality can be restored in them.

"This new discovery opens up an entirely new area of research. 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.

Belmonte admits that manipulation of Wnt signalling in humans is not possible at this point, but hopes that the new findings may eventually offer insights into current research examining the ability of stem cells to build new human body tissues and parts.

"This is the reverse of how we currently are thinking of using stem cells therapeutically, so understanding this process could be very illuminating. It could be that we could use the Wnt signaling pathway to dedifferentiate cells inside a body at the site of a limb injury, and have them carry out the job of building a new structure," he says.

The researchers used inhibitory and excitatory factors for Wnt signalling in three groups of vertebrates, zebrafish and salamanders, frogs, and chicks, after they cut a limb from the experimental embryos.

In adult zebrafish and salamanders, they found that blocking Wnt signaling with the inhibitory factors, prevented normal regeneration. But when they treated mutant adult zebrafish that cannot regenerate with the excitatory agent, the ability to regenerate their fins was rescued.

In frogs, they observed that treatment with the excitatory agent after they had lost their regenerative capacity induced new limb growth.

They also found the excitatory factor successful in producing limb regeneration in embryos of chick, which are not known to be able to regrow limbs.

"The signal restarted the process, and genes that were involved in the initial development of the limb were turned back on. It is simply amazing," Belmonte said.

However, Belmonte noted that Wnt signaling might lead to cancer if activated for too long a period in these animals.

"This has to be done in a controlled way, with just a few cells for a specific amount of time. The fact is that this pathway is involved in cell proliferation, whether it is to generate or regenerate limbs, control stem cells, or produce cancer," he said.