P/Q-type voltage-gated calcium channels regulate calcium signaling and developmental myelination in oligodendrocyte lineage cells

Oligodendrocyte lineage cells (OLCs) are glia that arise as oligodendrocyte progenitor cells (OPCs) in the central nervous system (CNS) and may persist as progenitors or differentiate into myelin-producing oligodendrocytes (OLs). OLCs are sensitive to neuronal activity, which can influence myelin formation via activity-dependent myelination. Calcium influx in OLCs regulates many developmental processes, including stabilizing newly formed sheaths. OLCs possess P/Q-type voltage-gated calcium channels (VGCC) that contribute to calcium influx and mutations in these channels are implicated in a spectrum of neurological disorders, yet the functional significance of P/Q-type channels in OLCs is not well understood. In this study, we employ zebrafish to investigate the role of P/Q-type channels in OLCs in vivo during development. We use global and cell-type specific CRISPR/Cas9-mediated genome editing approaches in conjunction with live imaging and physiology to characterize the morphology and signaling properties of OLCs with mutated P/Q-type channel genes. P/Q-type channels are required for normal myelination in the developing CNS and mutants present with decreased amplitude sheath calcium transients, reduced myelin production, shorter myelin sheaths and blebbing membrane structures during development. These findings provide new insight into the role of P/Q-type calcium channels in regulating OLC development and myelination.