Grant: Operating Grant

Most of the cells of our body are held together by a "glue" made of special "adhesion molecules". During embryonic development, and later even in the adult, cells must modify their relative positions relative to neighbors. In extreme cases such as cancer invasion, cells can even leave the tumor of origin and penetrate through other tissues. Such rearrangements required the adhesive bonds to be dynamically formed and undone. This is a fundamental question in Cell Biology that has remained largely unsolved. We study the separation of embryonic tissues from the initial homogenous mass of embryonic cells. This is not only a key event in the organization of the future organism, but also an excellent model to investigate the mechanisms through which cells can "recognize" cells to which they should bind from the ones they should keep at bay. This property seems to be somehow lost or bypassed by invasive cancer cells. We have recently discovered that the separation of early tissues is controlled by specific cell surface "sensors" that react when they touch cells of another type. This triggers a local retraction that temporarily pulls cells part, thus preventing intermingling of the two tissues. We believe that this is a central mechanism that controls contacts between normal and cancer cells as well. We have now for the first time a model where cells naturally undergo constant cycles of attachment and detachment. This proposal aims at determining how these "repulsive reactions" are able to disrupt the tight attachments formed between the two cells: are the adhesive bonds simply ripped apart by the sheer force of the cells retracting? Or are they on the contrary "melted" by a well-controlled disengagement of the adhesion molecules? And if so, what are the signals and the genes involved? The frog embryos used in this project are uniquely suited to combine molecular manipulations and biochemical studies with direct live observation of the dynamics of adhesive bonds.