bcatenin_mechanics · Mechanical activation of beta-catenin signalling

During embryonic morphogenesis, cells do not only generate forces necessary for shape changes and tissue movement but also sense and respond to the forces exerted on them by neighbouring cells and tissues. Recent studies demonstrate, that these forces can act as mechanical cues during development regulating cytoskeletal remodelling, cell proliferation and gene expression. However, in most cases the molecular mechanism by which cells sense and transduce a mechanical signal into a biochemical signal remains to be discovered. Therefore, my proposed project aims at identifying the primary mechanosensitive element during Drosophila gastrulation that initiates the activation of the beta-catenin pathway in stomodeal cells in response to mechanical strain that leads to the release of beta-catenin from adherens junctions (AJ) and its translocation to the nucleus, where it activates the transcription of a key regulator gene. In order to identify the molecular mechanism that translates a mechanical strain signal into a biochemical signal I will analyse the AJ complex in vivo for molecular changes in its dynamic interaction and conformation upon mechanical deformation during gastrulation. For this, I will make use of advanced fluorescent microscopy techniques in conjunction with classical biochemical assays. In addition, I will perform in vitro two cell assays to determine the strength and type of deformation needed to induce a conformational change. Ultimately, the information gained about the mechanosensitive element will be used to design a fluorescent probe to directly monitor the mechano-activation in response to the morphogenetic movements during Drosophila gastrulation. To my knowledge, this would be the first time in vivo to visualise directly the activation of a primary mechanosensor.