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Microtubule dynamics play a crucial role in neuronal morphogenesis.Microtubule-associated protein tau promotes microtubule assembly, stabilization and bundling.Tau forms cross-bridges between microtubules and plays important roles in axonal microtubule organization.However, the molecular mechanisms of tau-mediated regulation of microtubule dynamics remain largely unknown.Pacsin1, specifically expressed in the brain, is well reported to be involved in endocytosis, actin organization and membrane tubulation, but its function in neuronal microtubule dynamics has not been explored.Here, we report that pacsinl directly interacts with tau via its proline rich domain, and negatively regulates microtubule dynamics.In pacsinl-blocked DRG neurons, tau is abundant in the central domain of the growth cones, contributing to straight/spread microtubules.Overexpression of pacsinl suppresses the microtubule bundling ability of tau, so that microtubules become bent and loop-shaped.Furthermore, in cultured mouse DRG neurons, either increasing the expression level or blocking pacsin 1 leads to shorter axons and higher number of branches.The effects are compromised when the function ofpacsinl and tau are simultaneously blocked, indicating that pacsin1 regulates neuronal morphogenesis through tau.Taken together, our data suggest that the interaction between tau and pacsinl regulates microtubule dynamics, which in turn influences axonal elongation and branching.