Epithelium Formation: Cellular Adhesion Regulation in 3D

Most internal organs consist of a monolayer of polarized epithelial cells surrounding a central lumen that establish a barrier that segregates the internal medium from the outside environment. One of the key determinants in establishing apicobasal polarity in epithelial cells is the Scribble complex. The Scribble complex is a multi-protein scaffolding platform which functions by recruiting other binding partners, to build spatially distinct signaling complexes.

 

Our poor understanding of the basic mechanisms that control the function of the Scribble complex represents one of the major barriers to understand the formation of the epithelium.

 

In this talk, we will discuss how we use a combination of biochemical and imaging approaches, including both live and fix imaging of cells grown both in 2D and 3D, to characterize the molecular mechanisms that control SGEF-mediated downregulation of E-cadherin and ZO-1, cell-cell junctions’ stability, and barrier function in both 2D monolayers and 3D cysts. Our results delineate the role SGEF plays at multiple levels in controlling E-cadherin expression.

 

Learning Objectives