Abstract
Tadpoles of the frog Xenopus laevis can regenerate tails except for a short "refractory" period in which they heal rather than regenerate. Rapid and sustained production of ROS by NADPH oxidase (Nox) is critical for regeneration. Here, we show that tail amputation results in rapid, transient activation of the ROS-activated transcription factor NF-κB and expression of its direct target cox2 in the wound epithelium. Activation of NF-κB is also sufficient to rescue refractory tail regeneration. We propose that bacteria on the tadpole's skin could influence tail regenerative outcomes, possibly via LPS-TLR4-NF-κB signaling. When raised in antibiotics, fewer tadpoles in the refractory stage attempted regeneration, whereas addition of LPS rescued regeneration. Short-term activation of NF-κB using small molecules enhanced regeneration of tadpole hindlimbs, but not froglet forelimbs. We propose a model in which host microbiome contributes to creating optimal conditions for regeneration, via regulation of NF-κB by the innate immune system.