Xenopus tadpoles are a unique model for regeneration in that they exhibit two distinct phases of age-specific regenerative competence. In Xenopus laevis, young tadpoles fully regenerate following major injuries such as tail transection, then transiently lose regenerative competence during the “refractory period” from stages 45–47. Regenerative competence is then regained in older tadpoles before being permanently lost during metamorphosis. Here we show that a similar refractory period exists in X. tropicalis. Notably, tadpoles lose regenerative competence gradually in X. tropicalis, with full regenerative competence lost at stage 47. We find that the refractory period coincides closely with depletion of maternal yolk stores and the onset of independent feeding, and so we hypothesized that it might be caused in part by nutrient stress. In support of this hypothesis, we find that cell proliferation declines throughout the tail as the refractory period approaches. When we block nutrient mobilization by inhibiting mTOR signaling, we find that tadpole growth and regeneration are reduced, while yolk stores persist. Finally, we are able to restore regenerative competence and cell proliferation during the refractory period by abundantly feeding tadpoles. Our study argues that nutrient stress contributes to lack of regenerative competence and introduces the X. tropicalis refractory period as a valuable new model for interrogating how metabolic constraints inform regeneration.

爪蟾蝌蚪是一种独特的再生模型，因为它们表现出两个不同阶段的年龄特异性再生能力。在非洲爪蟾中，幼蝌蚪在尾部横断等重大损伤后完全再生，然后在第 45-47 阶段的“不应期”期间暂时失去再生能力。然后在变态过程中永久丧失之前，再生能力在较老的蝌蚪中重新获得。在这里，我们表明热带 X.中存在类似的不应期。值得注意的是，蝌蚪在热带X.中逐渐失去再生能力，在第 47 阶段失去了完全的再生能力。我们发现不应期与母体蛋黄储存的消耗和独立喂养的开始密切相关，因此我们假设它可能部分是由营养压力引起的。为了支持这一假设，我们发现随着不应期的临近，整个尾部的细胞增殖都会下降。当我们通过抑制 mTOR 信号传导来阻止养分动员时，我们发现蝌蚪的生长和再生减少，而蛋黄储存持续存在。最后，我们能够通过大量喂养蝌蚪来恢复不应期的再生能力和细胞增殖。我们的研究认为，营养压力导致缺乏再生能力并引入了热带 X.不应期作为一种有价值的新模型，用于研究代谢限制如何影响再生。