STUDY THE ROLE OF MICRO-NICHES IN EPITHELIAL APLICAL-BASAL POLARISATION

Abstract

Epithelia apical-basal polarisation is important for the formation of a selective barrier. This thesis developed a novel micro-well based mini-organ approach to decouple the chemical and physical parameters, to control the 3-D micro-niches, and quantitatively assessed the localization of key polarity markers. This thesis work has reported that at single cell level, lateral input of cell-cell adhesion cue in a 3-D micro-niche is crucial for the formation of apically localized “zonula adherens” belt structure identified by an actin belt, together with PAR-3, N-WASP, ZO-1 and Claudin-3, but not supported by cell-matrix adhesion cues alone. 2-D input of cell-cell adhesion cues also induced an edge localized E-cadherin and actin belt. Taken together, this thesis demonstrates that cell-cell adhesion cues in 3-D and 2-D micro-niches are sufficient to develop “zonula adherens” like belt formation at single cell level, and creates a novel tool to quantitatively imaging and analysis of key polarity markers.