Cdc42 And RhoA Can Mediate Both Attractive And Repulsive Axon Guidance By Extracellular Factors

We have examined the role of Rho family of GTPases in mediating axon guidance by extracellular factors. Expression of either dominant negative (DN) or constitutively active (CA) Cdc42 in cultured Xenopus spinal neurons abolished the chemoattractive turning of their growth cones induced by a gradient of brain-derived neurotrophic factor (BDNF), whereas chemorepulsion induced by a gradient of lysophosphatidic acid (LPA) was abolished by the expression of DN-RhoA and converted to chemoattraction by the expression of CA-Cdc42. Results on the effects of inhibitors of Rho kinase inhibitor and myosin light chain kinase further support an instructive role of Rho GTPases in axon guidance and the existence of distinct but partially convergent pathways mediated by Cdc42 and RhoA, each capable of triggering either attractive or repulsive turning of the growth cone.