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Signalling and crosstalk of Rho GTPases in mediating axon guidance

Nature Cell Biology volume 5, pages 38–45 (2003)Cite this article

Abstract

Axon extension during development of the nervous system is guided by many factors, but the signalling mechanisms responsible for triggering this extension remain mostly unknown. Here we have examined the role of Rho family small guanosine triphosphatases (GTPases) in mediating axon guidance by diffusible factors. Expression of either dominant-negative or constitutively active Cdc42 in cultured Xenopus laevis spinal neurons, at a concentration that does not substantially affect filopodial formation and neurite extension, abolishes the chemoattractive growth cone turning induced by a gradient of brain-derived neurotrophic factor that can activate Cdc42 and Rac in cultured neurons. Chemorepulsion induced by a gradient of lysophosphatidic acid is also abolished by the expression of dominant-negative RhoA. We also show that an asymmetry in Rho kinase or filopodial initiation across the growth cone is sufficient to trigger the turning response and that there is a crosstalk between the Cdc42 and RhoA pathways through their converging actions on the myosin activity essential for growth cone chemorepulsion.

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Figure 1: Growth cone turning induced by a gradient of BDNF or LPA.
Figure 2: Effect of toxin B on neurite extension and filopodial activity.
Figure 3: Rho GTPase expression in Xenopus embryos and spinal neurons.
Figure 4: Regulation of Rho GTPases by BDNF and effect of mutant Cdc42 and RhoA.
Figure 5: RhoA- and ROCK-dependent neurite inhibition induced by LPA.
Figure 6: Role of actin and myosin in filopodial dynamics.
Figure 7: Effects of Y-27632, ML-7 and BDM on growth cone turning responses.
Figure 8: Model of Cdc42- and RhoA-mediated growth cone guidance.

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Acknowledgements

We thank G. Ming and M. Ruchhoeft for communicating unpublished results; D. Turner, A. Hall and G. Bokoch for providing cDNA clones; and Yoshitomi Pharmaceuticals for Y-27632. This work was supported by grants from the Major State Basic Research Program of China and the Shanghai Science and Technology Development Foundation. M-m.P. was supported in part by a grant from the NIH.

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  1. Xiao-bing Yuan, Ming Jin and Xiaohua Xu: These authors contributed equally to this work

Authors and Affiliations

  1. Institute of Neuroscience, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai, 200031, China

    Xiao-bing Yuan, Ming Jin, Xiaohua Xu, Yuan-quan Song, Chien-ping Wu, Mu-ming Poo & Shumin Duan

  2. Division of Neurobiology, Department of Molecular and Cell Biology, University of California, Berkeley, 94720-3200, California, USA

    Mu-ming Poo

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Yuan, Xb., Jin, M., Xu, X. et al. Signalling and crosstalk of Rho GTPases in mediating axon guidance. Nat Cell Biol 5, 38–45 (2003). https://doi.org/10.1038/ncb895

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