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

Nature volume 403, pages 89–93 (2000)Cite this article

Abstract

Guidance of developing axons involves turning of the motile tip, the growth cone, in response to a variety of extracellular cues1,2. Little is known about the intracellular mechanism by which the directional signal is transduced. Ca2+ is a key second messenger in growth cone extension3,4 and has been implicated in growth-cone turning5,6. 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.

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Figure 1: Spatially restricted FLIP of caged molecules.
Figure 2: Attractive turning of Xenopus growth cones induced by repetitive FLIP of NP-EGTA.
Figure 3: Attractive and repulsive turning of a Xenopus growth cone induced by direct focal increase in [Ca2+]i in different extracellular solutions.
Figure 4: Fluorescence imaging of focal increase in [Ca2+]i induced by FLIP of NP-EGTA.

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Acknowledgements

I thank R. Maki Fitzsimonds (Yale University, New Haven, Connecticut, USA) and J. Alder (University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey, USA) for their critical review and comments on the manuscript, and J. Gibney for technical support. The initial part of this study was performed at the Marine Biological Laboratory (Woods Hole, Massachusetts, USA) with the support of a Nikon summer fellowship. This work was supported by a grant from the National Institutes of Health.

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  1. Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, 08854, New Jersey, USA

    James Q. Zheng

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Correspondence to James Q. Zheng.

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Zheng, J. Turning of nerve growth cones induced by localized increases in intracellular calcium ions. Nature 403, 89–93 (2000). https://doi.org/10.1038/47501

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