Early bioelectric activities mediate redox-modulated regeneration

Fernando Ferreira, Guillaume Luxardi, Brian Reid, Min Zhao

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Reactive oxygen species (ROS) and electric currents modulate regeneration; however, the interplay between biochemical and biophysical signals during regeneration remains poorly understood. We investigate the interactions between redox and bioelectric activities during tail regeneration in Xenopus laevis tadpoles. We show that inhibition of NADPH oxidase-mediated production of ROS, or scavenging or blocking their diffusion into cells, impairs regeneration and consistently regulates the dynamics of membrane potential, transepithelial potential (TEP) and electric current densities (JI) during regeneration. Depletion of ROS mimics the altered TEP and JI observed in the non-regenerative refractory period. Short-term application of hydrogen peroxide (H2O2) rescues (from depleted ROS) and induces (from the refractory period) regeneration, TEP increase and JI reversal. H2O2 is therefore necessary for and sufficient to induce regeneration and to regulate TEP and JI. Epistasis assays show that voltage-gated Na+ channels act downstream of H2O2 to modulate regeneration. Altogether, these results suggest a novel mechanism for regeneration via redoxbioelectric orchestration.

Original languageEnglish (US)
Pages (from-to)4582-4594
Number of pages13
JournalDevelopment (Cambridge)
Volume143
Issue number24
DOIs
StatePublished - Dec 15 2016

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Keywords

  • Electric current density
  • Membrane potential
  • NADPH oxidases
  • Reactive oxygen species
  • Regeneration
  • Transepithelial potential
  • Voltage-gated Na channels
  • Xenopus laevis

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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