Piller, M. | Search bioRxiv

bioRxiv2025

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.

neuroscience↗

bioRxiv2022

Cd59 and inflammation orchestrate Schwann cell development

Efficient neurotransmission is essential for organism survival and is enhanced by myelination. However, the genes that regulate myelin and myelinating glial cell development have not been fully characterized. Data from our lab and others demonstrates that cd59, which encodes for a small GPI-anchored glycoprotein, is highly expressed in developing zebrafish, rodent, and human oligodendrocytes (OLs) and Schwann cells (SCs), and that patients with CD59 dysfunction develop neurological dysfunction during early childhood. Yet, the function of CD59 in the developing nervous system is currently undefined. In this study, we demonstrate that cd59 is expressed in a subset of developing SCs. Using cd59 mutant zebrafish, we show that developing SCs proliferate excessively, which leads to reduced myelin volume, altered myelin ultrastructure, and perturbed node of Ranvier assembly. Finally, we demonstrate that complement activity is elevated in cd59 mutants and that inhibiting inflammation restores SC proliferation, myelin volume, and nodes of Ranvier to wildtype levels. Together, this work identifies Cd59 and developmental inflammation as key players in myelinating glial cell development, highlighting the collaboration between glia and the innate immune system to ensure normal neural development.

neuroscience↗