Early redox activities modulate Xenopus tail regeneration.

Area of Science:

• Developmental Biology
• Regenerative Medicine
• Cellular Physiology

Background:

• Reactive oxygen species (ROS) are vital for regeneration, but their interaction with oxygen (O2) and hypoxia-inducible factors (HIF) is not fully understood.
• Understanding these interactions is key to unlocking regenerative potential.

Purpose of the Study:

• To elucidate the interplay between O2, ROS, and HIF in Xenopus laevis tadpole tail regeneration.
• To identify the molecular mechanisms governing regeneration initiation and progression.

Main Methods:

• Utilized an optic-based probe (optrode) to measure spatiotemporal O2 influx.
• Investigated the effects of inhibiting ROS production and scavenging on O2 influx.
• Examined the role of HIF-1α stabilization and inhibition in regeneration.
• Analyzed downstream targets of HIF-1α, including heat shock protein 90 and electric current reversal.

Main Results:

• Observed elevated O2 influx immediately post-amputation, correlating with tail regeneration.
• Inhibition of ROS production, but not scavenging, reduced O2 influx.
• HIF-1α inhibition impaired regeneration, while its stabilization promoted regeneration during the refractory period.
• Hypoxia, O2 influx, ROS production, and HIF-1α stabilization were correlated within the regeneration bud.

Conclusions:

• Regeneration is driven by a coordinated mechanism involving O2 influx, ROS production, and HIF-1α stabilization.
• Heat shock protein 90 and electric current reversal are identified as downstream effectors of HIF-1α in this process.
• This study provides novel insights into the molecular regulation of appendage regeneration.