Dynamic remodelling of cadherin contacts in embryonic mesenchymal cells during differential cell migration

Abstract

AbstractA fundamental aspect of morphogenesis is the capacity of cells to actively exchange neighbours while maintaining the overall cohesion of the tissue. These cell rearrangements require the dynamic remodelling of cadherin cell adhesions. Many studies have examined this process in tissues where it is driven by the joint action of cell protrusions and actomyosin contraction along the shrinking junction. However, cell rearrangements can also occur through differential migration. This mode of cell rearrangement, characteristic of mesenchymal tissues, is much less well understood. Here, we explore the prototypical case of the gastrulating Xenopus prechordal mesoderm, and provide the first detailed analysis at how cadherin contacts are remodelled and eventually disrupted in this type of tissue. Using a reductionist approach, including analysis of single contacts using a dual pipette aspiration setup, we unveil two concurrent mechanisms. Most cadherins are removed via “peeling”, i.e. disruption of the trans bonds and lateral diffusion out of the contact. In parallel, a remnant of cadherins concentrates at the shrinking contact, which is ultimately resolved by breakage of the link with the actin cytoskeleton, showing that the weakest link shifts at different stages of contact remodelling. Additionally, we observe recruitment of myosin peripheral to the shrinking contact, which influences the efficiency of the final detachment. Finally, manipulation of cortical tension indicates that the process is sensitive to the magnitude and orientation of the forces applied on the contact, revealing another key relationship between cell-cell adhesion and the cortical cytoskeleton. This study unravels a new modality of cell contact dynamics, which is likely to be widely relevant for highly migratory mesenchymal tissues.