Injury-induced Erk1/2 signaling tissue-specifically interacts with Ca2+ activity and is necessary for regeneration of spinal cord and skeletal muscle

Abstract

The transition of stem cells from quiescence to proliferation enables tissues to self-repair. The signaling mechanisms driving these stem-cell-status decisions are still unclear. Ca²⁺ and the extracellular signal-regulated kinase (Erk1/2) are two signaling pathways that have the potential to coordinate multiple signals to promote a specific cellular response. They both play important roles during nervous system development but their roles during spinal cord and muscle regeneration are not fully deciphered. Here we show in Xenopus laevis larvae that both Ca²⁺ and Erk1/2 signaling pathways are activated after tail amputation. In response to injury, we find that Erk1/2 signaling is activated in neural and muscle stem cells and is necessary for spinal cord and skeletal muscle regeneration. Finally, we show in vivo that Erk1/2 activity is necessary for an injury-induced increase in intracellular store-dependent Ca²⁺ dynamics in skeletal muscle-associated tissues but that in spinal cord, injury increases Ca²⁺ influx-dependent Ca²⁺ activity independent of Erk1/2 signaling. This study suggests that precise temporal and tissue-specific activation of Ca²⁺ and Erk1/2 pathways is essential for regulating spinal cord and muscle regeneration.

Keywords: Calcium; Extracellular signal-regulated kinase; In vivo; Regeneration; Skeletal muscle; Spinal cord.