Signalling and crosstalk of Rho GTPases in mediating axon guidance.
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.
Yuan
Xiao-bing
XB
Institute of Neuroscience, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.
Jin
Ming
M
Xu
Xiaohua
X
Song
Yuan-quan
YQ
Wu
Chien-ping
CP
Poo
Mu-ming
MM
Duan
Shumin
S
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000502:physiology; D007700:Kinetics; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011554:Pseudopodia / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D014982:Xenopus laevis; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D018076:DNA, Complementary; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins