Cytoskeletal/junction relationships during epithelial remodeling events

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The cell surface is the interface between cells and their environment. Interactions at this interface enable cells to generate movement, to assume specific shapes, to carry out specific functions, and to form multicellular structures. It is not surprising that major elements of the cytoskeleton within animal cells are related to the cell surface, particularly to regions of the surface involved in forming connections both with neighboring cells and with supporting substrates. The long-term objective of my research program is to explore the interaction between intercellular junctions and the cytoskeleton in cells within the context of tissues, and determine how the two systems function together to generate complex remodeling events in cell layers (epithelia) that line the many tubes and cavities in animals. We are particularly interested in how the cytoskeleton and junctions interact to allow cells to detach from their neighbors and to move through epithelia from one compartment of the body to another. Over the next five years we will explore the mechanism by which the cytoskeleton and junctions function to move developing sperm cells through the seminiferous epithelium of the mammalian testis, and to release fully formed sperm cells from this epithelium. We will focus on cytoskeleton-related tubular structures that we propose are sub-cellular machines that internalize and degrade intact intercellular junctions during the extensive epithelial remodeling events that occur during the production of sperm cells. We will characterize these structures at the molecular level and determine if their function is required for the successful movement of the next generation of developing sperm cells further into the epithelium. Our results have already generated a paradigm shift in how biologists view junction disassembly related to sperm release. Over the next few years we anticipate that our results will generate a similar shift in how biologists view the movement of the next generation of developing sperm cells from one compartment to another in the seminiferous epithelium.