INHIBITION OF AXONAL GROWTH BY SNAP-25 ANTISENSE OLIGONUCLEOTIDES IN-VITRO AND IN-VIVO

AXONAL elongation and the transformation of growth cones to synaptic t erminals are major steps of brain development and the molecular mechan isms involved form the basis of the correct wiring of the nervous syst em. The same mechanisms may also contribute to the remodelling of nerv e terminals that occurs in the adult brain, as a morphological substra te to memory and learning1. We have investigated the function of the n erve terminal protein SNAP-25 (ref. 2) during development. We report h ere that SNAP-25 is expressed in axonal growth cones during late stage s of elongation and that selective inhibition of SNAP-25 expression pr events neurite elongation by rat cortical neurons and PC-12 cells in v itro and by amacrine cells of the developing chick retina in vivo. The se results demonstrate that SNAP-25 plays a key role in axonal growth. They also suggest that high levels of SNAP-25 expression in specific areas of the adult brain2 may contribute to nerve terminal plasticity.