Mechanisms of axonal plasticity.

GAP-43 plays an important role in axonal plasticity by guiding growth cones rather than supporting axonal elongation. In Purkinje cells that show no regenerative responses and no GAP-43 expression after axotomy, the simple addition of GAP-43 gene induces the formation of branched plexuses typical of sprouting growth. Purkinje cells can express some growth-associated proteins, but never GAP-43, when axotomy is made very close to cell body or when an antibody for the myelin-associated inhibitory molecules is applied to intact cells both in vivo and in vitro. Also in these conditions they are unable to show new axonal profiles even in a permissive environment that allows inferior olive cells to regenerate and reinnervate their target cells. We suggest that GAP-43 is a key molecule to initiate axon growth while other genes are necessary to develop a full regenerative program.