Directed growth cone movement, mainly an actin-based cell motility, guides the pathfinding of a growing neurite during the formation of nervous system. A growth cone is the motile and growing tip of an axon and the site of decision-making in axonal pathfinding. It consists of two distinct structures: the long, finger-like projections called filopodia and the veil-like protrusions called lamellipodia. Filopodia and lamellipodia have been shown to play different roles in axonal pathfinding: filopodia act as antennae that detect and respond to the environment while lamellipodia provide the major site for adhesive contacts and the mechanical basis for growth cone motility. Previous studies demonstrated that specific actin-associated proteins and actin-based motors function in specific aspects of filopodial and lamellipodial motility, suggesting that sets of proteins act together to generate and control actin-based motility in growth cone pathfinding. Our goals are to illustrate the function of individual members of myosin superfamily in filopodial and lamellipodial motility and in growth cone turning. To accomplish the objective, chromophore-assisted laser inactivation (CALI) technique in combination with advanced live cell imaging techniques, micromanipulations, and molecular techniques and various pharmacological inhibitors will be employed to dissect the function of myosins in vivo. Advancement of our studies will offer insight into the role of myosins in axonal pathfinding and cellular motility in general, enhance our understanding of the molecular mechanisms underlying the neuronal outgrowth and axonal pathfinding, and help in finding cues for spinal cord injuries and loss of function caused by neurological disorders.
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