Microtubule networks in zebrafish hair cells facilitate presynapse transport and fusion during development

Sensory cells in the retina and inner ear rely on specialized ribbon
synapses for neurotransmission. Disruption of these synapses is linked to
visual and auditory dysfunction, but it is unclear how these unique
synapses are formed. Ribbon synapses are defined by a presynaptic density
called a ribbon. Using live-imaging approaches in zebrafish, we find that
early in hair-cell development, many small ribbon precursors are present
throughout the cell. Later in development, fewer and larger ribbons
remain, and localize at the presynaptic active zone (AZ). Using tracking
analyses, we show that ribbon precursors exhibit directed motion along an
organized microtubule network towards the presynaptic AZ. In addition, we
show that ribbon precursors can fuse together on microtubules to form
larger ribbons. Using pharmacology, we find that microtubule disruption
interferes with ribbon motion, fusion, and normal synapse formation.
Overall, this work demonstrates a dynamic series of events that underlies
formation of a critical synapse required for sensory function.