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In vivo regulation of axon extension and pathfinding by growth-cone calcium transients

An Erratum to this article was published on 06 May 1999

Abstract

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 cues1,2. The intracellular calcium concentration ([Ca2+]i) of growth cones correlates with motility in vitro3,4,5,6,7, 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+ transients 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 pathfinding8,9,10, 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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Figure 1: Rapid assembly and simple structure of the embryonic Xenopus spinal cord visualized in confocal Z-series reconstructions of immun.
Figure 2: The rate of axon extension is inversely proportional to the frequency of spontaneous Ca2+ transients.
Figure 3: Suppression or imposition of Ca2+ transients with photoactivatable compounds alters rates of axon extension.
Figure 4: Growth cones directly approaching the VLF generate increased frequencies of Ca2+ transients and stall before turning onto.

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Acknowledgements

We thank S. Watt and I. Hsieh for technical assistance, and M. Ferrari and M.-M. Poo for comments on the manuscript. Research supported by a NIH NINDS fellowship to T.M.G. and grant to N.C.S.

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Gomez, T., Spitzer, N. In vivo regulation of axon extension and pathfinding by growth-cone calcium transients. Nature 397, 350–355 (1999). https://doi.org/10.1038/16927

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