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Adaptation in the chemotactic guidance of nerve growth cones

Abstract

Pathfinding by growing axons in the developing nervous system may be guided by gradients of extracellular guidance factors. Analogous to the process of chemotaxis in microorganisms, we found that axonal growth cones of cultured Xenopus spinal neurons exhibit adaptation during chemotactic migration, undergoing consecutive phases of desensitization and resensitization in the presence of increasing basal concentrations of the guidance factor netrin-1 or brain-derived neurotrophic factor. The desensitization is specific to the guidance factor and is accompanied by a reduction of Ca2+ signalling, whereas resensitization requires activation of mitogen-associated protein kinase and local protein synthesis. Such adaptive behaviour allows the growth cone to re-adjust its sensitivity over a wide range of concentrations of the guidance factor, an essential feature for long-range chemotaxis.

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Figure 1: Turning of nerve growth cones induced by a gradient of netrin-1.
Figure 2: Desensitization and resensitization of turning responses.
Figure 3: Zig-zag pathfinding of the growth cone.
Figure 4: Heterologous desensitization between netrin-1 and BDNF.
Figure 5: Calcium signals induced by a netrin-1 gradient correlate with adaptation.
Figure 6: Activation of MAPK by netrin-1 and BDNF, and involvement of MAPK in growth-cone chemotaxis.
Figure 7: Effects of protein synthesis inhibition.
Figure 8: A model of growth-cone adaptation in a gradient of guidance cues.

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Acknowledgements

Chick recombinant netrin-1 was provided by M. Tessier-Lavigne. This work was supported by grants from the NIH.

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Correspondence to Mu-ming Poo.

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Ming, Gl., Wong, S., Henley, J. et al. Adaptation in the chemotactic guidance of nerve growth cones. Nature 417, 411–418 (2002). https://doi.org/10.1038/nature745

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