NGS PhD Oral Defense Series

Cell-substrate Adhesion and Cell-cell Junction Coordination in Epithelial Cell Extrusion

by Le Anh Phuong

Supervisor(s): Prof Lim Chwee Teck,  Prof Benoit Ladoux
Chairperson: A/Prof Low Boon Chuan

Date / Time: 19 November 2018 at 4pm
Venue: Meeting Room T203, University Hall, Tan Chin Tuan Wing, 21 Lower Kent Ridge Road, Level 2

Please be present at least 10 mins prior to the start of Oral Defense and sign on the attendance sheet. Thank you for your kind consideration and cooperation.

ABSTRACT
Apoptotic extrusion is a coupled process when a cell undergoes apoptosis and actively removed from the epithelia. This process is crucial in maintaining epithelial homeostasis and has implications in diseases pertaining to epithelial tissues like cancer and asthma. Extrusion is mechanically-regulated when the neighboring cells could use either lamellipodia-based protrusion or contractile cable (purse-string) to actively remove the dying cells. The preference of one mode over another was found to be dependent on the density of the monolayer. However, little is known about how much each of these two modes contribute to the overall effectiveness of extrusion, and what determines one mode of extrusion over the other. The force arises during extrusion is poorly understood. Here we shown that during extrusion at highly packed tissue, the formation of contractile actomyosin cables are anisotropic, which is contradictory to previous belief that the actomyosin cable is formed in a uniform manner. Concurrently, there were also lamellipodia-based protrusion observed. The existence of these two mechanisms results in an anisotropic force field surrounding extrusion site. By manipulating α-Catenin, a mechano-sensing component of adherent junction, we demonstrated that the reduced cell-cell junction favors the neighboring cells’ decision to form lamellipodia protrusion. On the other hand, cells with strengthened cell-cell junction formed more actomyosin cable; the contractility was also enhanced to effectively extrude the dying cells when cell-substrate adhesion was removed. Our results highlighted the importance of previously-undermined lamellipodia-based protrusion in extrusion, which ensures the complete closure during extrusion. We also demonstrated by tuning cell-cell junction strength of cell-substrate adhesion pattern, we could control one mode over the other as well as the timing of actomyosin cable.