Spatio-Temporal Patterning of Mechano-Chemical Signals during Collective Cell Migration

Abstract

During collective migration of epithelial cells, leader cells show sustained ERK activity, while follower cells exhibit oscillatory ERK activation in conjunction with the intercellular propagation of the ERK activity. These different ERK activations govern the spatiotemporal organization of cell specification and coordinated movement. By employing the visualization and manipulation of cell signaling activity with biosensors and optogenetic tools, we revealed that free space-dependent cell protrusions and intercellular pulling forces are required for the ERK activation dynamics in the leader and follower cells, respectively. These findings highlight the novel aspects of growth factor signaling pathways dependent on physical and mechanical stimuli.