The role of localized instability of the actin network in specifying axonal
fate was examined with the use of rat hippocampal neurons in culture. Duri
ng normal neuronal development, actin dynamics and instability polarized to
a single growth cone before axon formation. Consistently, global applicati
on of actin-depolymerizing drugs and of the Rho-signaling inactivator toxin
B to nonpolarized cells produced neurons with multiple axons. Moreover, di
sruption of the actin network in one individual growth cone induced its neu
rite to become the axon. Thus, local instability of the actin network restr
icted to a single growth cone is a physiological signal specifying neuronal
polarization.