Dissecting the molecular mechanisms of epithelial architecture and plasticity – ARCHIPLAST

This project aims at deciphering the molecular mechanisms of epithelial stability and remodelling. Epithelia are composed of polarized cells with junctions segregating apical and lateral surfaces. They serve essential functions in separating different physiological environments in the adult. At the same time, epithelia are extensively remodelled during development and regeneration. Understanding how cell junctions both maintain the polarized architecture of epithelial cells and their ability to change shape and neighbours is a very important problem in cell and developmental biology. Perturbations in the balance between robustness and plasticity in epithelial organization are associated with severe disorders such as Epithelial Mesenchymal Transition (EMT) or tissue invasiveness in solid tumour progression.
Here we will use the Drosophila embryo as a model system to address this issue. Epithelia share conserved characteristics and proteins in vertebrates and invertebrates and Drosophila is a very powerful system to understand how epithelia form, how their polarity is maintained and how cell mechanical properties are regulated during tissue remodelling. We will more specifically study cell intercalation, a process where polarized junction remodelling drives tissue extension, and cell constriction, which participates in tissue invagination. Both processes require actomyosin networks with distinctive contractile dynamic properties, and adherens junctions to anchor tensile activity and transmit forces during cell shape changes.
We will focus our efforts on the 2 most important properties of epithelia that are required for epithelial stability and remodelling: adhesion controlled by E-cadherin, and force generation by actomyosin networks, as well as their transmission at the cortex. The goal is to understand how tissue level dynamics emerges from subcellular regulation of adhesion and contractility.
We will use a range of approaches, from molecular genetics, biochemistry, quantitative imaging and mechanical perturbations to understand i) what signals control ability to constrict or to intercalate via regulation of Myo-II contractility; ii) how planar polarity is regulated in intercalating cells; iii) how E-cadherin distribution and dynamics are regulated, in particular via endocytosis and exocytosis; iv) what mechanisms are responsible for different properties of contractile actomyosin networks, namely constriction or stabilization and v) whether and if so how cells mechanically coordinate their contractile properties at the tissue level.
We expect that these results will shed light on how epithelial plasticity emerges from the coordination between adhesion and contractility at cell junctions.