The evolution of the axonal transport toolkit

Neurons are highly polarized cells that critically depend on long‐range, bidirectional transport between the cell body and synapse for their function. This continual and highly coordinated trafficking process, which takes place via the axon, has fascinated researchers since the early 20th century. Ramon y Cajal first proposed the existence of axonal trafficking of biological material after observing that dissociation of the axon from the cell body led to neuronal degeneration. Since these first indirect observations, the field has come a long way in its understanding of this fundamental process. However, these advances in our knowledge have been aided by breakthroughs in other scientific disciplines, as well as the parallel development of novel tools, techniques and model systems. In this review, we summarize the evolution of tools used to study axonal transport and discuss how their deployment has refined our understanding of this process. We also highlight innovative tools currently being developed and how their addition to the available axonal transport toolkit might help to address key outstanding questions. Long‐range axonal transport is critical for neuronal homeostasis and function. Since its discovery, advances in understanding axonal trafficking have been aided by scientific discoveries in other disciplines, as well as the development of novel tools, techniques and model systems. In this review, we discuss the evolution of the tools used to investigate axonal transport and how they have furthered our understanding of this process. Furthermore, we highlight innovative probes that could potentially be added to this ever‐expanding toolkit.