Investigation the Role of Cadherin and Integrin during Epithelial Cell Rearrangements
Epithelia are robust tissues whose mechanical cohesion requires the formation of cell-cell adhesive contacts supported by adherens junctions (AJs), mainly composed of E-Cadherin clusters stabilized by actomyosin filaments. The mechanical sealing properties of epithelia are constantly challenged by cell-cell rearrangements that occur during delamination, intercalation and cell division. During these events, E-Cadherin contacts are dismantled, yet neighbor exchange occurs without the tissue tearing apart. The interplay between actomyosin contractility and the remodelling of AJs are proposed to be sufficient to mechanically support these multicellular rearrangements. However, and unexpectedly, we discovered that during cell intercalation and cytokinesis in the Drosophila pupal epithelium, focal adhesions (FAs) containing alpha-, beta-integrin receptors and Talin, are transiently assembled at sites of AJ remodeling. AJs and FAs are two main adhesive structures that ensure the formation of robust mechanical contacts enabling the transmission of cytoskeletal force to support changes in cell and tissue shape. Using state-of-the-art genetic, super-resolution imaging and biophysical approaches, we propose to study the assembly of FAs, their connection to actomyosin force generation and their functions during cytokinesis and cell intercalation in invertebrate and vertebrates model systems. Our working hypothesis is that the cleavage furrow ingression at cytokinesis and the junction shrinkage during cell intercalation cause a shear stress that triggers the local dismantling of AJs and, concomitantly, the assembly of FAs, in the plane of AJs. This multidisciplinary proposal will provide a comprehensive understanding of the cooperation and interdependence between cadherin and integrin-mediated intercellular adhesion required to ensure tissue tensional homeostasis.
Le séminaire aura lieu vendredi 29 mars à 11h 45 en salle François Jacob (Institut Jacques Monod – 15 rue Hélène Brion 75013 Paris)