Identifying mechanisms of mechanosensation in the Drosophila notum that contribute to the control of epithelial junction remodelling. (360G-Wellcome-092840_Z_10_A)

When two epithelial cells make contact they form a stable cell adhesion complex that finally results in the formation of an epithelium. However when two mesenchymal cells make contact the outcome is completely different: they do not form a permanent adhesion complex and very frequently they move away from each other in a behavior called contact inhibition of locomotion [1]. Intriguingly, cell adhesion molecules such as cadherins are known to be involved in both kinds of cell interaction. The formation and dynamics of the adhesion complex in epithelial cells has been extensively studied [2], but the study of cell-cell interactions and cell adhesion in mesenchymal cells has been rather neglected. The aim of this project is to compare cell adhesion complex formation between epithelial cells and between mesenchymal cells, in order to understand the different outcomes of these two cell interactions. This knowledge would help us to better understand important processes such as epithelial-to-mesenchymal transition and contact inhibition of locomotion; two cell behaviors that are central to both cancer metastasis and cell migration during embryo development. We will use two embryonic cell populations whose behavior has been very well characterized in our lab: neural crest (as a mesenchymal cell type) and placode cells (as an epithelial cell type). Most of the experiments will be performed using Xenopus cells cultured in vitro, but we will also analyze cell behavior in vivo, using zebrafish and Xenopus embryos. The cell adhesion complex has been well characterized in epithelial cells, and several key molecules have been described, such as cadherins, catenins, and elements of the cytoskeleton like actin and myosin. In addition, the regulation of small GTPases, such as RhoA and Rac, has been shown to be essential for the formation and maintenance of epithelial junctions. In this project, we will study in placode (epithelial) and neural crest (mesenchymal) cells: i) the dynamic localization of molecules of the cell adhesion complex during cell contact ii) the dynamics of small GTPases during cell contact and their regulation by elements of the adhesion complex. iii) From the above experiments we expect to find the key elements that regulate the different outcome of epithelial and mesenchymal cell-cell contacts. Based on these results, we will perform functional studies with these molecules in order to change a mesenchymal cell-cell contact into an epithelial interaction and vice versa.