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

Abstract

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.