The locomotion of the nerve growth cone during development or regeneration is thought to be important for steering a growing neurite down the correct pathway to its target. This process is essential for normal development or functional recovery aftter nerve damage. Nerve growth cone locomotion is a complex phenomenon which has been best studied in cell culture. To understand the underlyng mechanism responsible for nerve growth cone locomotion, a multidisciplinary approach will be taken. Rat superior cervical ganglion neurons grown in cell culture will be used. Working under the assumption that actin and myosin are involved in growth cone motility, immunoelectron microscopy will seek to determine the molecular organization of growth cone myosin and actin. Microinjection of monoclonal antibodies to myosin will be used to determine the role of myosin in the production of contractile tension that moves the growth cone across a substratum. Fluorescence ratio imaging of growth cone calcium using the specific indicator fura-2 will then be done to determine the role calcium plays in the control of the moility mechanism. These experiments will provide a basic framework for understanding the mechanism of guided locomotion.
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