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

Nat Cell Biol. 2013 Feb;15(2):222-8. doi: 10.1038/ncb2659. Epub 2013 Jan 13.

Abstract

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, through the coordinated activity of numerous growth factor signalling pathways, including the Wnt, Fgf, Bmp, Notch and TGF-β pathways. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Amputation
  • Animals
  • Animals, Genetically Modified
  • Antioxidants / pharmacology
  • Cell Proliferation* / drug effects
  • Enzyme Inhibitors / pharmacology
  • Fibroblast Growth Factors / metabolism
  • Gene Expression Regulation
  • Hydrogen Peroxide / metabolism
  • Larva / metabolism
  • NADPH Oxidases / antagonists & inhibitors
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism
  • Oligonucleotides, Antisense / metabolism
  • Reactive Oxygen Species / metabolism*
  • Regeneration* / drug effects
  • Tail / drug effects
  • Tail / embryology
  • Tail / metabolism*
  • Tail / surgery
  • Time Factors
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway
  • Xenopus Proteins / metabolism
  • Xenopus laevis / embryology
  • Xenopus laevis / genetics
  • Xenopus laevis / metabolism*
  • Xenopus laevis / surgery
  • beta Catenin / metabolism

Substances

  • Antioxidants
  • CTNNB1 protein, Xenopus
  • Enzyme Inhibitors
  • Oligonucleotides, Antisense
  • Reactive Oxygen Species
  • Wnt Proteins
  • Xenopus Proteins
  • beta Catenin
  • fibroblast growth factor 20, Xenopus
  • Fibroblast Growth Factors
  • Hydrogen Peroxide
  • NADPH Oxidases