Appendage regeneration relies on the formation of blastema, a heterogeneous cellular structure formed at the injury site. However, little is known about the early injury-activated signaling pathways that trigger blastema formation during appendage regeneration. Here, we provide compelling evidence that the extracellular signal–regulated kinase (ERK)–activated casein kinase 2 (CK-2), which has not been previously implicated in appendage regeneration, triggers blastema formation during leg regeneration in the American cockroach, Periplaneta americana. After amputation, CK-2 undergoes rapid activation through ERK-induced phosphorylation within blastema cells. RNAi knockdown of CK-2 severely impairs blastema formation by repressing cell proliferation through down-regulating mitosis-related genes. Evolutionarily, the regenerative role of CK-2 is conserved in zebrafish caudal fin regeneration via promoting blastema cell proliferation. Together, we find and demonstrate that the ERK-activated CK-2 triggers blastema formation in both cockroach and zebrafish, helping explore initiation factors during appendage regeneration.

中文翻译：

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ERK 激活的 CK-2 在附属物再生过程中触发芽基形成

附肢再生依赖于芽基的形成，芽基是在损伤部位形成的异质细胞结构。然而，人们对在附肢再生过程中触发芽基形成的早期损伤激活的信号通路知之甚少。在这里，我们提供了令人信服的证据，证明细胞外信号调节激酶 (ERK) 激活的酪蛋白激酶 2 (CK-2) 在美洲大蠊 (Periplaneta americana) 的腿部再生过程中触发胚基形成，此前并未涉及该蛋白激酶 2 (CK-2 )。截肢后，CK-2 通过 ERK 诱导的胚基细胞内磷酸化而快速激活。 RNAi 敲低CK-2可通过下调有丝分裂相关基因来抑制细胞增殖，从而严重损害胚基形成。从进化角度来看，CK-2 的再生作用通过促进胚基细胞增殖而在斑马鱼尾鳍再生中得以保留。我们共同发现并证明，ERK 激活的 CK-2 会触发蟑螂和斑马鱼胚基的形成，有助于探索附肢再生过程中的启动因素。