Developmental regulation of Erk signaling by mitotic kinases.

Abstract

During the peri-implantation phase of murine embryogenesis, the epiblast proliferates rapidly and undergoes epithelialization. At the same time, the preimplantation pluripotent state transforms into a more developmentally advanced, pregastrulation state. While extensive research has elucidated cell-extrinsic signals that direct the developmental progression, such as the Fgf/Mek/Erk pathway, the potential interplay of intrinsic cellular cues remains largely unexplored. To address this, we conducted a comprehensive phenotypic screen using an in vitro model of epiblast development. We identified aurora kinase A as a cell-intrinsic factor contributing to Erk activation and transcriptional response. Consequently, suppressing aurora kinase A activity delayed exit from naïve pluripotency. Moreover, our results show that upon entry into mitosis, Erk relocates to the cell division machinery. We found that in dividing cells, a fraction of Erk, with yet elusive functions, localizes on the centrosomes, where its phosphorylation depends on polo-like kinase 1.