TY - JOUR TI - Cd59 and inflammation regulate Schwann cell development AU - Wiltbank, Ashtyn T AU - Steinson, Emma R AU - Criswell, Stacey J AU - Piller, Melanie AU - Kucenas, Sarah A2 - Feltri, M Laura A2 - Stainier, Didier YR VL - 11 PY - 2022 DA - 2022/06/24 SP - e76640 C1 - eLife 2022;11:e76640 DO - 10.7554/eLife.76640 UR - https://doi.org/10.7554/eLife.76640 AB - 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 and nerves may have 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. KW - Schwann cell KW - myelin KW - node of Ranvier KW - CD59 KW - complement KW - inflammation JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -