Cellular mechanisms of embryonic boundary during notochord formation in enopus

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We are requesting funds to study the process of separation of embryonic tissues. Newly formed tissues become delineated by so-called embryonic boundaries, which prevents cell mixing and are thus crucial to maintain theorganization of the embryo. Very little is known about the cellular mechanisms at work at the boundary. Understanding the mechanisms that maintain the coherence of a tissue and prevent cell mixing between different cell types is of general importance, including for human disease. Indeed, such processes appear to be de-regulated in cancer metastasis, where tumor cells can leave the tissue of origin and penetrate other tissues. We use the early frog embryo as a model, because it is easily accessible to experimentation and inexpensive. Most molecules are very similar between frogs and humans, and results obtained in our model can be readily used in other, medically relevant, model systems. In the previous granting period, we have been able to visualize directly cells while in the process of sorting, i.e. moving to the correct side of the boundary. We have discovered that that cells can still cross the boundary several hours after its formation, demonstrating that this structure is surprisingly permeable to cell migration, underscoring the importance of cells acquiring and maintaining the precise tissue identity, since no physical barrier would otherwise be able to prevent them to entering the wrong tissue. We have also observed that the strength of the adhesiveness of a cell toward its neighbors can be significantly inhibited without affecting significantly the proper sorting at the boundary, an unexpected finding that contradicts a widely accepted model for tissue formation based on the adhesive properties of cells. Instead, we propose that cells know which behavior they have to adopt (i.e. mixing with similar cells, but not with cells from a different tissue) thanks to surface sensors that detect the identity of neighboring cells. Our goal is to identify the molecules that mediate such cell to cell recognition by contact, and to unravel the mechanisms triggered by these signals that regulate the cell behavior.