Zebrafish oligodendrocyte lineage cells use the postsynaptic protein Gephyrin to myelinate GABAergic axons and limit myelin sheath growth

Axon myelination can tune neuronal circuits through placement and modulation of different patterns of myelin sheaths on distinct types of axons. How myelin formation is coordinated on distinct axon classes remains largely unknown. Recent work indicates neuronal activity and vesicle release promote myelin formation, and myelin-producing oligodendrocytes express canonical postsynaptic factors that potentially facilitate oligodendrocyte-axon interaction for myelin ensheathment. Here, we examined whether the inhibitory postsynaptic scaffold protein Gephyrin (Gphn) mediates selective myelination of specific axon classes in the larval zebrafish. Consistent with this possibility, Gphn was enriched in myelin on GABAergic and glycinergic axons. In gphnb deficient larval oligodendrocytes, myelin sheaths were longer and the frequency of myelin placement on GABAergic axons was reduced. Collectively, our results indicate that oligodendrocyte lineage cells use Gphn to promote myelin formation on GABAergic axons and limit myelin sheath length. Myelin forms on axons of both inhibitory and excitatory neurons. Here the authors show that a classical neuronal postsynaptic protein, Gphn, functions in oligodendrocytes to promote inhibitory axon myelination in zebrafish.