Journal Article

Amputation-induced reactive oxygen species are required for successful Xenopus tadpole tail regeneration

Gallop, Jennifer L., Lea, Robert, Love, Nick R., Dorey, Karel, Kritsiligkou, Paraskevi, Amaya, Enrique, Koh, Yvette, Chen, Yaoyao, Ishibashi, Shoko

2013

Overview

Xenopus laevis and tropicalis tadpoles display incredible regenerative capacity of their tail. Amaya and colleagues find that tadpole tail amputation induces the production of reactive oxygen species (ROS) to induce cell proliferation and regeneration, through activation of the Wnt/β-catenin and Fgf20 signalling pathways. Understanding the molecular mechanisms that promote successful tissue regeneration is critical for continued advancements in regenerative medicine. Vertebrate amphibian tadpoles of the species Xenopus laevis and Xenopus tropicalis have remarkable abilities to regenerate their tails following amputation 1 , 2 , through the coordinated activity of numerous growth factor signalling pathways, including the Wnt, Fgf, Bmp, Notch and TGF-β pathways 3 , 4 , 5 , 6 . Little is known, however, about the events that act upstream of these signalling pathways following injury. Here, we show that Xenopus tadpole tail amputation induces a sustained production of reactive oxygen species (ROS) during tail regeneration. Lowering ROS levels, using pharmacological or genetic approaches, reduces the level of cell proliferation and impairs tail regeneration. Genetic rescue experiments restored both ROS production and the initiation of the regenerative response. Sustained increased ROS levels are required for Wnt/β-catenin signalling and the activation of one of its main downstream targets, fgf20 (ref.  7 ), which, in turn, is essential for proper tail regeneration. These findings demonstrate that injury-induced ROS production is an important regulator of tissue regeneration.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/136/2091 / 631/136/532/489 / 631/80/86 / Amphibians / Amputation / Amputation, Surgical / Animals / Animals, Genetically Modified / Antioxidants - pharmacology / beta Catenin - metabolism / Cancer Research / Cell Biology / Cell Proliferation - drug effects / Developmental Biology / Enzyme Inhibitors - pharmacology / Fibroblast Growth Factors - metabolism / Gene Expression Regulation / Genetic aspects / Hydrogen Peroxide - metabolism / Larva - metabolism / letter / Life Sciences / Medical research / NADPH Oxidases - antagonists & inhibitors / NADPH Oxidases - genetics / NADPH Oxidases - metabolism / Oligonucleotides, Antisense - metabolism / Oxygen / Physiological aspects / Reactive oxygen species / Reactive Oxygen Species - metabolism / Regeneration (Biology) / Regeneration - drug effects / Stem Cells / Tail - drug effects / Tail - embryology / Tail - metabolism / Tail - surgery / Tennis / Time Factors / Tissue engineering / Upstream / Vertebrates / Wnt Proteins - metabolism / Wnt Signaling Pathway / Xenopus laevis / Xenopus laevis - embryology / Xenopus laevis - genetics / Xenopus laevis - metabolism / Xenopus laevis - surgery / Xenopus Proteins - metabolism / Xenopus tropicalis