The growth of the axon is not dependent upon net microtubule assembly at its distal tip

Although there is agreement that the net addition of new microtubule polymer to the axon is required for its growth, controversy exists concerning the principal site in the neuron where this occurs. Some models hold that microtubule polymer is assembled within the cell body and translocated down the axon, while others hold that the net addition of polymer occurs at the distal tip of the axon. The foundation for the latter idea was a study in which anti-microtubule drugs were applied topically for 30 min to discrete regions of cultured sensory neurons (Bamburg et al., 1986). The axon continued to grow when the drugs were applied to the cell body, but stopped growing when the drugs were applied to the distal tip of the axon. Assuming that the sole action of the drug was to inhibit microtubule assembly, many workers have interpreted these findings as indicating that the growth of the axon requires net microtubule assembly at its distal tip. We repeated these experiments using a broader range of drug treatments, and evaluated using electron microscopy the effects of these treatments on microtubule levels. Our results indicate that the previous drug treatments went beyond inhibiting microtubule assembly, and also caused substantial microtubule disassembly. When the drug regime was altered so as to induce lower levels of microtubule disassembly in the distal region of the axon, the axon continued to grow. These results indicate that the growth of the axon is not dependent upon net microtubule assembly at its distal tip.