MBI PhD Oral Defense

Time: 3pm
Date: Tuesday, 4 December 2018
Venue: MBI, level 5 meeting rooms

Supervisor: Prof Yusuke TOYAMA

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

by Minnah THOMAS, Toyama’s Group

Mechanical coupling of epithelia enables coordination of collective tissue movements during different developmental and physiological processes. During apoptosis in epithelia, the dying cell is expelled by coordinated processes in both the dying cell and neighbours. Apoptotic cell extrusion is driven by both actomyosin cable constriction and lamellipodial crawling in the neighbours. Throughout cell extrusion, mechanical coupling of epithelia needs to be maintained to preserve tissue homeostasis. Although much is known about the regulation of adherens junction 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. The pre-existing DJ recruited radial cytokeratin-18 filaments and reoriented the keratin network during constriction. The DJ was proximate to the actomyosin cable at early constriction; and subsequently decoupled from the cable during its basolateral movement suggesting a mechanical coupling between the two. Molecular perturbation studies indicated that DJ is required to facilitate both constriction and de novo junction formation. We propose that desmosome influences junctional myosin driven tissue dynamics during extrusion. This study shows the pivotal role of desmosome in facilitating collective tissue dynamics to ensure epithelial sheet integrity during apoptotic cell extrusion.

**Please note the examination following the seminar is closed-door**