A critical role for a Rho-associated kinase, p160ROCK, in determining axonoutgrowth in mammalian CNS neurons

We tested the contribution of the small GTPase Rho and its downstream targe t p160ROCK during the early stages of axon formation in cultured cerebellar granule neurons, p160ROCK inhibition, presumably by reducing the stability of the cortical actin network, triggered immediate outgrowth of membrane r uffles and filopodia, followed by the generation of initial growth cone-lik e membrane domains from which axonal processes arose. Furthermore, a potent iation in both the size and the motility of growth cones was evident, thoug h the overall axon elongation rate remained stable. Conversely, overexpress ion of dominant active forms of Rho or ROCK was suggested to prevent initia tion of axon outgrowth. Taken together, our data indicate a novel role for the Rho/ROCK pathway as a gate critical for the initiation of axon outgrowt h and the control of growth cone dynamics.