Control of microtubule assembly in growth cones.

Growth cones are transient structures present at the tips of growing axons and dendrites (neurites). They are crucial to neuronal development because of their pathfinding ability and their role in synaptogenesis (reviewed by Dodd and Jessell, 1988). In the last few years it has become apparent that growth cones are also involved in the assembly of the cytoskeleton of the elongating neurite (reviewed by Gordon-Weeks, 1989, 1991). We are particularly interested in the assembly of microtubules in the growth cone and its importance for neurite advance. The microtubules in the neurite are bundled into fascicles, presumably by the cross-linking action of microtubule-associated proteins (MAPs), and on entering the growth cone they splay out like the ribs of a fan with their 'plus' ends, the ends at which assembly takes place preferentially, oriented distally. Within the growth cone there is a large pool of assembly competent tubulin that provides subunits for microtubule elongation. Several observations point to the existence of precise mechanisms controlling assembly of this soluble tubulin pool. If the control mechanisms are disrupted the ability of the neurite to advance is severely compromised. We have examined the possibility that MAPs are important components in this control mechanism. Many of the known MAPs are present within growth cones, including MAP 1B, MAP 2 and tau. Experiments with neuronal cultures and growth cones isolated as a subcellular fraction from developing rat brain point particularly toward the phosphorylated form of MAP 1B as an essential component in the concerted assembly of microtubules at the growth cone and in particular in the bundling of microtubules in the neurite.