Cellular and molecular responses-mediated by DjMEK1/2 are necessary for planarian regeneration

The planarian flatworm is an ideal model to study the regeneration due to its robust regenerative ability. A variety of cellular response activities have been reported to be involved in the regeneration process, including the mitogen-activated protein kinase (MAPK) signaling. However, the mechanism of MAPK pathway in regenerative responses is still unclear. In this study, we employed the planarian, Dugesia japonica, as the model to investigate the function of MAP-extracellular signal-regulated kinase (MEK), an important component of MAPK signaling pathway, in the regeneration process. We found that MEK was required for the missing tissue response after several amputation and subsequent regeneration. MEK not only affected the size of blastema in the early stage of regeneration by regulating stem cell proliferation, but also determined the planarian's regeneration through balancing cell proliferation and apoptosis. In addition, the activation of Wnt pathway partially rescued regenerative defects induced by inhibition of MEK. Taken together, our results highlight a crucial role of MEK signaling in the planarian regeneration.