EXCEED THE SPACE PROVIDED, Cell migration is central to many biological and pathological processes, including embryogenesis, the inflammatory response, tissue repair and regeneration, cancer, arthritis, atherosclerosis, osteoporosis, and congenital developmental brain defects. Not surprisingly, there is considerable interest in understanding the molecular basis of cell migration since this could lead to the development of novel therapeutic strategies for various pathological processes. However, understanding migration is challenging, because migration requires the integration and temporal coordination of many different processes, including the formation and disassembly of adheieins, that occur in spatially distinct locations within the cell. While considerable progress has been made in identifying molecules that mediate migration, the localized targeting, activation and inactivation of the regulatory components and the mechanisms by which they modulate the formation and breakdown of adhesions are now key issues that are only beginning to be addressed. Recent imaging technologies provide great promise for addressing adhesive mechanisms in cells migrating both in vivo and in vitro by providing useful assays for measuring the kinetics by which components enter and leave adhesions, polarized targeting of adhesion components, and the dynamics of cellular components throughout the cell. In this application we propose to use these new imaging technologies and assays to determine the relative kinetics by which components enter and leave adhesions and identify the mechanisms used to targeting components to and from adhesions. We will focus on two cell types, neurons and fibroblasts, since the former is highly motile and the later has adhesions that are readily visualized, and a prioritized list of signaling and structural molecules that include integrins, FAK, GITI, PAK, and zyxin. In addition we will characterize novel migration related adhesion molecules that have emerged from novel visual screens of migration, and translate our research on dissociated cells migrating in culture to nerve and mucle precursors migrating in vivo. PERFORMANCE SITE ========================================Section End===========================================
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