British scientists have made a surprising discovery after studying how tadpoles of the African clawed frog (Xenopus laevis) and the Western clawed frog (Xenopus tropicalis) re-grow their tails. The discovery could have big implications for research into human healing and regeneration.
Top: tadpole and adult of Xenopus tropicalis. Bottom: tadpole and adult of Xenopus laevis. Scalebar – 1 mm (Uffe Hellsten et al., 2010)
It is generally appreciated that frogs and salamanders have remarkable regenerative capacities, in contrast to mammals. If a tadpole loses its tail a new one will regenerate within a week.
For several years, a team led by Prof Enrique Amaya of the University of Manchester has been trying to better understand the regeneration process in the hope of eventually using this information to find new therapies that will improve the ability of humans to heal and regenerate better.
In an earlier study, the team identified which genes were activated during tail regeneration. That research showed that several genes that are involved in metabolism are activated, in particular those that are linked to the production of reactive oxygen species – chemically reactive molecules containing oxygen. What was unusually about those findings is that the reactive oxygen species are commonly believed to be harmful to cells.
The team then decided to follow up on this unexpected result. To examine the reactive oxygen species during tail regeneration, the scientists measured the level of hydrogen peroxide, a common reactive oxygen species in cells, using a fluorescent molecule that changes light emission properties in the presence of hydrogen peroxide.
The scientists were able to show that a marked increase in hydrogen peroxide occurs following tail amputation and interestingly, they showed that the hydrogen peroxide levels remained elevated during the entire tail regeneration process, which lasts several days.
“We were very surprised to find these high levels of the reactive oxygen species during tail regeneration. Traditionally, the reactive oxygen species have been thought to have a negative impact on cells. But in this case they seemed to be having a positive impact on tail re-growth,” Prof Amaya said.
To assess how vital the presence of the reactive oxygen species are in the regeneration process, the team limited production of reactive oxygen species using two methods. The first was by using chemicals, including an antioxidant, and the second was by removing a gene responsible for the production of reactive oxygen species. In both cases the regeneration process was inhibited and the tadpole tail did not grow back.
“When we decreased levels of reactive oxygen species, tissue growth and regeneration failed to occur. Our research suggests that reactive oxygen species are essential to initiate and sustain the regeneration response.”
“We also found that production of reactive oxygen species is essential to activate Wnt signalling, which has been implicated in essentially every studied regeneration system, including those found in humans. It was also striking that our study showed that antioxidants had such a negative impact on tissue re-growth, as we are often told that antioxidants should be beneficial to health,” said Prof Amaya, who reported the discovery in a paper published in the journal Nature Cell Biology.
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Bibliographic information: Love NR et al. Amputation-induced reactive oxygen species are required for successful Xenopus tadpole tail regeneration. Nature Cell Biology, published online 13 January, 2013; doi: 10.1038/ncb2659
