Investigating the Role of Desmosome and Intermediate Filaments in Apoptotic Cell Extrusion

Abstract

Apoptotic cell extrusion, which involves expulsion of a dead cell in epithelia, is driven by both actomyosin cable constriction and lamellipodial crawling in the neighbours. Throughout cell extrusion, intercellular coupling needs to be maintained to preserve tissue homeostasis. Although much is known about adherens junction regulation during this process, the role of desmosome junction (DJ) remains poorly understood. In this thesis, we used a combination of laser-based apoptosis induction and live confocal imaging in cultured epithelial monolayers to study DJs during extrusion. We show that DJ retains junctional coupling at the tissue interface throughout extrusion until formation of de novo junctions between apposing neighbours. Live imaging showed suggestive mechanical coupling/decoupling of desmosome and actomyosin during different phases of constriction. We concluded that DJ functions by regulating both constriction and intercellular coupling during extrusion. This study shows an example of the pivotal role of desmosome in facilitating collective tissue dynamics.