In vivo regulation of axon extension and pathfinding by growth-cone calcium transients.
Gomez, Timothy M.; Spitzer, Nicholas C.
[Letter] Nature. 397(6717):350-355, January 28, 1999.

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Growth cones at the tips of extending neurites migrate through complex environments in the developing nervous system and guide axons to appropriate target regions using local cues [1,2].The intracellular calcium concentration ([Ca2 ]i) of growth cones correlates with motility in vitro [3-7], but the physiological links between environmental cues and axon growth in vivo are unknown. Here we report that growth cones generate transient elevations of [Ca2 ]i as they migrate within the embryonic spinal cord and that the rate of axon outgrowth is inversely proportional to the frequency of transients. Suppressing Ca2 transients by photorelease of a Ca2 chelator accelerates axon extension, whereas mimicking transients with photorelease of Ca2 slows otherwise rapid axonal growth. The frequency of Ca2 slows is cell-type specific and depends on the position of growth cones along their pathway. Furthermore, growth-cone stalling and axon retraction, which are two important aspects of pathfinding [8-10], are associated with high frequencies of Ca2 transients. Our results indicate that environmentally regulated growth-cone Ca2 transients control axon growth in the developing spinal cord.

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