Neuroscience Graduate Program, University of Virginia, Charlottesville, United States.
Program in Fundamental Neuroscience, University of Virginia, Charlottesville, United States.
Elife. 2022 Jun 24;11:e76640. doi: 10.7554/eLife.76640.
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 , 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 is expressed in a subset of developing SCs. Using 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 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.
有效的神经传递对于生物体的生存至关重要，而髓鞘形成则可以增强神经传递。然而，调节髓鞘形成和髓鞘形成胶质细胞发育的基因尚未得到充分表征。我们实验室和其他实验室的数据表明，编码一种小的 GPI-锚定糖蛋白的 CD59 在发育中的斑马鱼、啮齿动物和人类少突胶质细胞 (OLs) 和施万细胞 (SCs) 中高度表达，并且 CD59 功能障碍的患者在幼儿期会出现神经功能障碍。然而，Cd59 在发育中的神经系统中的功能目前尚不清楚。在这项研究中，我们证明了 CD59 在发育中的施万细胞中表达。使用 突变的斑马鱼，我们表明发育中的施万细胞过度增殖，神经可能具有减少的髓鞘体积、改变的髓鞘超微结构和干扰的Ranvier 结组装。最后，我们证明了补体活性在 突变体中升高，并且抑制炎症可以将施万细胞增殖、髓鞘体积和 Ranvier 结恢复到野生型水平。总之，这项工作确定了 Cd59 和发育性炎症是髓鞘形成胶质细胞发育的关键因素，强调了胶质细胞和先天免疫系统之间的合作，以确保正常的神经发育。
