Myogenic dedifferentiation involves a p53-dependent reorganization of PLK4 localization during centrosome regeneration

Abstract

Multinucleated skeletal muscle cells are stably withdrawn from the cell cycle in most vertebrates. Muscle dedifferentiation is however naturally occurring during limb regeneration in newts and can be artificially induced in mammalian myotubes. Dedifferentiation involves fragmentation of myofibers and myotubes into mononucleate cells which subsequently reenter the cell cycle, and give rise to proliferative progeny. Here we addressed the dynamics of centrosomes, which are key organelles for cell proliferation during myogenic differentiation and dedifferentiation. We show that, in contrast to their mammalian counterparts, newt muscle cells retain centrosomes during differentiation and demonstrate that regeneration of centrosomes in dedifferentiated mouse muscle cells depends on inhibition of the tumor suppressor p53. We also find that regulation of the subcellular localization of Polo-Like Kinase 4 rather than its expression level is a hallmark of myogenic differentiation and dedifferentiation, identifying a novel cellular process underlying the plasticity of the differentiated state.