During organ regeneration, after the initial responses to injury, gene expression patterns similar to those in normal development are reestablished during subsequent morphogenesis phases. This supports the idea that regeneration recapitulates development and predicts the existence of genes that reboot the developmental program after the initial responses. However, such rebooting mechanisms are largely unknown. Here, we explore core rebooting factors that operate during Xenopus limb regeneration. Transcriptomic analysis of larval limb blastema reveals that hoxc12/c13 show the highest regeneration specificity in expression. Knocking out each of them through genome editing inhibits cell proliferation and expression of a group of genes that are essential for development, resulting in autopod regeneration failure, while limb development and initial blastema formation are not affected. Furthermore, the induction of hoxc12/c13 expression partially restores froglet regenerative capacity which is normally very limited compared to larval regeneration. Thus, we demonstrate the existence of genes that have a profound impact alone on rebooting of the developmental program in a regeneration-specific manner.

在器官再生过程中，在对损伤做出最初反应后，在随后的形态发生阶段重新建立与正常发育中相似的基因表达模式。这支持了这样的观点，即再生概括了发育，并预测了在初始反应后重新启动发育程序的基因的存在。然而，这种重启机制在很大程度上是未知的。在这里，我们探索爪蟾肢体再生过程中起作用的核心重启因素。幼虫肢体芽基的转录组分析表明，hoxc12/c13在表达中表现出最高的再生特异性。通过基因组编辑敲除它们中的每一个都会抑制细胞增殖和一组对发育至关重要的基因的表达，导致自足再生失败，而肢体发育和初始芽基形成不受影响。此外， hoxc12/c13表达的诱导部分恢复了幼蛙的再生能力，与幼虫再生相比，这种能力通常非常有限。因此，我们证明了基因的存在，这些基因仅对以再生特异性方式重新启动发育程序产生深远影响。