Relating division, migration, and cell signaling during collective cell migration

Epithelial monolayers provide critical barrier functions for multicellular organisms and are among the most well-studied collective systems, maintaining strong cell-cell adhesion and exhibiting coordinated outwards growth. While much is known about the biomechanics of how force generation and substrate stiffness affect such collective motion, how cells collectively share information during migration is less clear. The ERK signaling pathway is key for many forms of cell-cell signaling, and here we study the interplay between ERK signaling, collective migration, and tissue proliferation in epithelia. Using the ERK-KTR reporter, we show that tissue migration induces both periodic, rapid ERK signals propagating back into the tissue from the leading edge, as well as slower domains of ERK activity propagating towards the leading edge. We hypothesize that this slower ERK signal is correlated with the spatiotemporal cell proliferation pattern. Complementing these studies are additional experiments we have performed on E-cadherin substrates that mimic cell-cell adhesion signaling. These substrates show extremely low motility due to a low active fluctuation state and further regulate cell cycle dynamics by mimicking cell-cell information.