Cross-limb communication during Xenopus hindlimb regenerative response: non-local bioelectric injury signals

Regeneration of damaged body parts requires coordination of size, shape, location and orientation of tissue with the rest of the body. It is not currently known to what extent injury sites communicate with the remaining soma during repair, or what information may emanate from the injury site and reach other regions. We examined the bioelectric properties (resting potential gradients in the epidermis) of Xenopus laevis froglets undergoing hindlimb amputation and observed that the contralateral (undamaged) limb exhibits apparent depolarization signals immediately after the opposite hindlimb is amputated. The pattern of depolarization matches that of the amputated limb and is correlated to the position and type of injury, revealing that information about damage is available to remote body tissues and is detectable non-invasively in vivo by monitoring the bioelectric state. These data extend knowledge about the electrophysiology of regenerative response, identify a novel communication process via long-range spread of injury signaling, a phenomenon that we call bioelectric injury mirroring, and suggest revisions both to regenerative medicine and diagnostic strategies that are focused entirely on the wound site, and to the use of contralateral limbs as controls.