Salamanders and zebrafish can grow new limbs and fins, but chop off your own finger, and it’s not going to grow back. Now researchers in San Diego have been able to regenerate wings in chicken embryos, which can’t normally grow new limbs. The findings move scientists one step closer to understanding how to induce regenerative powers in humans.
“Regeneration likely involves a combination of factors,” says Stephen Badylak, a scientist at the McGowan Institute for Regenerative Medicine, in Pittsburgh, PA, who is not involved in the research. “If we can identify the key ones and put them together, we can probably induce regeneration.”
When a salamander loses a leg, specialized epithelial cells cover the wound, forming a multilayered structure. These cells then trigger the muscle, nerve, and connective-tissue cells below to dedifferentiate (essentially, lose the specialized characteristics that make them a neuron or muscle cell), divide, and form a ball of stem-cell-like cells. The ball of cells begins to develop the way a normal limb does, forming new muscle and bone to produce an entirely new limb.
While many animals have this capacity–within the animal kingdom, more species can regenerate limbs than cannot–mammals have largely lost it. For reasons not yet clear, they instead form scars when wounded. But many developmental biologists believe that if they can understand the regeneration process, they will be able to induce it in humans. The process could potentially repair damaged tissue, such as occurs in cardiac muscle after a heart attack, or even spur the growth of new limbs.
Researchers have now identified a genetic “on” switch that triggers regeneration at developmental stages when the animal normally lacks the capacity. Yasuhiko Kawakami and colleagues at the Salk Institute for Biological Studies, in La Jolla, CA, performed experiments in chickens and frogs in which they overactivated a set of genes, called the Wnt pathway, known to be involved in regular development and thought to be involved in regeneration. When the genes were turned on in chicken embryos that had had their developing wings removed, the action triggered the growth of a new limb. In frogs, which can regenerate limbs when they are tadpoles but not as adults, activating the genes extended the period of time that tadpoles could regenerate.
“We think that controlling activity of Wnt may have the potential for making tissue regenerate which normally does not regenerate,” says Kawakami, a developmental biologist who carried out the study with Juan Carlos Izpisua Belmonte, also at the Salk.