Turning of nerve growth cones induced by localized increases in intracellular calcium ions

Guidance of developing axons involves turning of the motile tip, the growth cone, in response to a variety of extracellular cues(1,2) Little is known about the intracellular mechanism by which the directional signal is transduced, Ca2+ is a key second messenger in growth cone extension(3,4) and has been implicated in growth-cone turning(5,6). Here I report that a direct, spatially restricted elevation of intracellular Ca2+ concentration ([Ca2+](i)) on one side of the growth cone by focal laser-induced photolysis (FLIP) of caged Ca2+ consistently induced turning of the growth cone to the side with elevated [Ca2+](i) (attraction). Furthermore, when the resting [Ca2+](i) at the growth cone was decreased by the removal of extracellular Ca2+, the same focal elevation of [Ca2+](i) by FLIP induced repulsion. These results provide direct evidence that a localized Ca2+ signal in the growth cone can provide the intracellular directional cue for extension and is sufficient to initiate both attraction and repulsion. By integrating local and global Ca2+ signals, a growth cone could thus generate different turning responses under different environmental conditions during guidance.