The Role of Claudins in Embryonic Patterning and Morphogenesis

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I am fascinated by the processes that direct the conversion of a simple one-cell fertilized egg into a complex three dimensional organism. Obviously, it is impossible to study all of the developmental events and processes that are involved. In this grant we are primarily focusing on understanding how cells that are adjacent to one in the epiblast determine whether they will become surface ectoderm that will eventually enclose the embryo or neural ectoderm that will contribute primarily to the central nervous system. These are two dramatically different fates and the balance of how many cells assume each fate must be controlled so that development can proceed normally. We are going to explore the role of the claudin family of tight junction proteins in this decision process. Tight junctions form at the apical surface of the cell, which in the case of the epiblast is in direct contact with the extraembryonic environment. Tight junctions act to link the cells to one another and create a barrier or seal that prevents the movement of molecules between the cells. Claudins are an integral component of the tight junction and in fact, they determine how tight a seal is made between the cells and what types of molecules can pass between the cells. We discovered that in the epiblast, there are different patterns of claudin expression. This suggests that within the epiblast cell layer, there are different micro-environments that differ in their selectivity of what can pass between the cells. We are going to investigate the relationship between these microenvironments and the cell fate decisions that determine whether a cell will contribute to the neural ectoderm or the surface ectoderm.