Cell biology of growth cone pathfinding

Phillip Gordon-Weeks

Emeritus Professor

During neuronal development, a diverse range of cellular processes, including neuronal migration, neuritogenesis, axon pathfinding, and dendritic spine development, depend on the co-ordinated activity of different components of the cytoskeleton, in particular the coupling of dynamic microtubules to actin filaments. The molecular mechanisms underlying these processes, the proteins involved and how they are regulated, are areas of current intense research. In my laboratory we are trying to understand how guidance molecules, such as those that attract migrating neurons and growth cones, signal to and influence the behaviour of the cytoskeleton that underlies directional responses. In growth cones, the dynamic interaction of microtubules with the actin filaments within filopodia determines growth cone turning, an essential behaviour during axonal pathfinding. We have shown that this behaviour depends on the direct interaction between EB3, a microtubule binding protein, located on the plus-ends of microtubules, and the actin filament-binding protein drebrin, bound to the proximal ends of filopodia actin filaments. Disruption of this interaction impairs neuronal migration, neuritogenesis and growth cone formation.

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