Genetic compensation response contributes to Pleurodeles waltl limb regeneration.

Hippo-Yap/Taz pathway is essential for tissue regeneration in multiple species. However, we found that in the highly regenerative salamanders, Yap knockout does not compromise the limb regeneration due to genetic compensation response (GCR). Specifically, the mutated Yap locus derived non-sense mRNA, which was recognized by UPF3A to instruct compensatory Taz induction. Blocking Yap mRNA or protein indeed inhibits regeneration. GCR could be utilized to maintain the robustness of limb regeneration.