Formation of a specialized wound epidermis is required to initiate salamander limb regeneration. Yet little is known about the roles of the early wound epidermis during the initiation of regeneration and the mechanisms governing its development into the apical epithelial cap (AEC), a signaling structure necessary for outgrowth and patterning of the regenerate. Here, we elucidate the functions of the early wound epidermis, and further reveal midkine (mk) as a dual regulator of both AEC development and inflammation during the initiation of axolotl limb regeneration. Through loss- and gain-of-function experiments, we demonstrate that mk acts as both a critical survival signal to control the expansion and function of the early wound epidermis and an anti-inflammatory cytokine to resolve early injury-induced inflammation. Altogether, these findings unveil one of the first identified regulators of AEC development and provide fundamental insights into early wound epidermis function, development, and the initiation of limb regeneration.

中文翻译：

---

Midkine是肢体再生启动过程中伤口表皮发育和炎症的双重调节剂

需要形成专门的伤口表皮来启动sal肢再生。关于再生过程中早期伤口表皮的作用以及控制其发展为顶上皮帽（AEC）的机制，人们所知甚少，而顶芽上皮帽（AEC）是再生产物长出和形成图案所必需的信号结构。在这里，我们阐明了早期伤口表皮的功能，并进一步揭示了midkine（mk）作为腋下肢再生开始期间AEC发育和炎症的双重调节剂。通过功能损失和获得功能的实验，我们证明了mk既是控制早期伤口表皮扩张和功能的关键生存信号，又是解决早期损伤引起的炎症的抗炎细胞因子。总而言之，这些发现揭示了最早发现的AEC发育调节剂之一，并为早期伤口表皮功能，发育和肢体再生的启动提供了基本见识。