Agrin has been found to be involved in axon extension, but the signaling triggered for this response remains unknown. Here we have examined the role of MuSK and Rac on neurite extension and axon guidance induced by agrin. Expression of either dominant negative or antisense MuSK in cultured Xenopus Laveis spinal neurons abolishes agrin-induced neurite outgrowth inhibition and converts chemorepulsive growth cone turning induced by a gradient of agrin into chemoattraction. Agrin inhibits Rac activity in developing neurons and expression of dominant negative Rac1 abolishes agrin-induced growth cone turning and substantially inhibits neurite extension.
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