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 form. Ribbon synapses are defined by a presynaptic density called a ribbon. Using live imaging in zebrafish hair cells, we find that numerous small ribbon precursors are present throughout the cell early in development. As development progresses, fewer large 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 to reach the presynaptic AZ. In addition, we show that ribbon precursors can fuse together on microtubules. 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 the formation of a critical synapse required for sensory function.