Cell Reintegration
Epithelial reintegration works in the same way as IgCAM-mediated axon growth and pathfinding; it relies not only on extracellular adhesion but also mechanical coupling between IgCAMs and the lateral spectrin-based membrane skeleton. Our work indicates that reintegration is mediated by a distinct epithelial adhesion assembly that is compositionally and functionally equivalent to junctions made between axons.
Our lab has pioneered the study of (re)integration, a cell behavior that protects epithelial tissues from disorganization.
Cells often become displaced from tissue layers following mitosis due to mechanical crowding, or errors in orienting the mitotic spindle. Misplaced mitotic daughter cells have the capacity to reintegrate back to parental tissue layers via reintegration. Reintegration is driven by cell adhesion molecules that localize at lateral cell cortices, in addition to intracellular cytoskeletal factors. These factors and the mechanisms that drive reintegration are the same as found in growing axons during neural development.
Reintegration appears to be a conserved morphogenetic process that occurs in multiple different animal epithelia. We are investigating the mechanism of cell reintegration using the Drosophila fruit fly model and mammalian cell culture and organoids.
Cells are normally born within the tissue plane, but loss of spindle orientation control can result in perpendicular divisions (shown at right). Homophilic adhesion factors drive the reintegration of misplaced cells by maximizing cell-cell adhesion along the lateral cortex.