ERK-activated CK-2 triggers blastema formation during appendage regeneration

• DOI: 10.1126/sciadv.adk8331
• Publication Date: 2024-03-20T17:59:03Z
• Authors: Xiao-Shuai Zhang; Lin Wei; Wei Zhang; Fei-Xue Zhang; Lin Li; Liang Li; Yejie Wen; Jia-Hui Zhang; Suning Liu; Dongwei Yuan; Yanmei Liu; Chonghua Ren; Sheng Li
• Keywords: Wound Healing; 0303 health sciences; 03 medical and health sciences; Animals; Regeneration; Biomedicine and Life Sciences; Zebrafish Proteins; Zebrafish; Signal Transduction

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.