Caliber of sensory axons in vivo varies spatially and temporally and is influenced by the cellular microenvironment

Cell shape is crucial to cell function, particularly in neurons. The cross-sectional diameter, also known as caliber, of axons and dendrites is an important parameter of neuron shape, best appreciated for its influence on the speed of action potential propagation. Most studies of axon caliber focus on cell-wide regulation and assume that caliber is static. Here, we have investigated local variation and dynamics of axon caliber in the peripheral axons of zebrafish touch-sensing neurons at embryonic stages, prior to sex determination. To obtain absolute measurements of caliber in vivo, we paired sparse membrane labeling with super-resolution microscopy of neurons in live fish. We found that axon segments had varicose or “pearled” morphologies, and thus vary in caliber along their length, consistent with reports from mammalian systems. Sister axon segments originating from the most proximal branch point in the axon arbor had average calibers that were largely independent of each other. Axon caliber tapered across the branch point, suggesting that action potential conductance may be favored in these afferent axons. Caliber was dynamic on the time-scale of minutes, and this dynamicity changed over the course of development. By measuring the caliber of axons adjacent to dividing epithelial cells, we found that the cellular microenvironment is one of potentially multiple drivers of axon caliber variation across space and time. Our findings raise the possibility that spatial and temporal variation in axon caliber could significantly influence neuronal physiology.