Identification of axon-oligodendrocyte preferential interaction sites preceding initial myelin sheath formation

Oligodendrocytes are matured oligodendrocyte progenitor cells that serve to myelinate axons within the central nervous system. The myelination process is complex and is orchestrated by many unknown mechanisms, of particular interest, the causal relationship between axon diameter and myelination. Previous studies suggest that oligodendrocytes preferentially myelinate axons with larger diameters. Due to the variation in axon diameter along the length of individual axons, we first hypothesized that oligodendrocytes interact with and initiate myelination at thicker domains of axons known as varicosities. To test this hypothesis, we performed in vivo time-lapse in zebrafish larvae to determine if oligodendrocytes preferentially interact with and sustain interactions at varicosities compared to intervening, thin axonal segments. These larvae expressed green and red fluorescent proteins in each cell type, enabling direct observation of oligodendrocyte-axon interaction over several hours. Oligodendrocytes more frequently interacted with varicosities as compared to intervening axonal segments. In addition, oligodendrocytes interacted with varicosity domains for more sustained periods of time as compared to intervening segments. Varicosities serve as sites of enriched synaptic vesicle release, which is instrumental in oligodendrocyte and axonal communication. Therefore, ongoing experiments are testing whether synaptic vesicle release is necessary to direct and stabilize oligodendrocyte interactions at these sites.https://openriver.winona.edu/urc2018/1031/thumbnail.jp