CAMP-INDUCED SWITCHING IN TURNING DIRECTION OF NERVE GROWTH CONES

Development of the nervous system depends on the correct pathfinding a nd target recognition by the growing tip of an axon, the growth cone(1 -3). Diffusible or substrate-bound molecules present in the environmen t may serve as either attractants or repellents to influence the direc tion of growth-cone extension(4-11). Here we report that differences i n cyclic-AMP-dependent activity in a neuron may result in opposite tur ning of the growth cone in response to the same guidance cue. A gradie nt of brain-derived neurotrophic factor normally triggers an attractiv e turning response of the growth cone of Xenopus spinal neurons in cul ture, but the same gradient induces repulsive turning of these growth cones in the presence of a competitive analogue of cAMP or of a specif ic inhibitor of protein kinase A. This cAMP-dependent switch of the tu rning response was also found for turning induced by acetylcholine, bu t not for the turning induced by neurotrophin-3 (NT-3). Thus, in the p resence of other factors that modulate neuronal cAMP-dependent activit y, the same guidance cue may trigger opposite turning behaviours of th e growth cone during its pathfinding in the nervous system.