Article abstract
Nature Cell Biology 5, 38 - 45 (2002)
Published online: 23 December 2002 | doi:10.1038/ncb895
Signalling and crosstalk of Rho GTPases in mediating axon guidance
Xiao-bing Yuan1,3, Ming Jin1,3, Xiaohua Xu1,3, Yuan-quan Song1, Chien-ping Wu1, Mu-ming Poo1,2 & Shumin Duan1
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.
- Institute of Neuroscience, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China. e-mail: shumin@ion.ac.cn
- Division of Neurobiology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200, USA. e-mail: yuanxb@ion.ac.cn
- These authors contributed equally to this work
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