Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, China.
Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, China.
Exp Neurol. 2021 Jan;335:113486. doi: 10.1016/j.expneurol.2020.113486. Epub 2020 Sep 28.
Myelination is extremely important in achieving neural function. Hypomyelination causes a variety of neurological diseases. However, little is known about how hypomyelination occurs. Here we investigated the effect of dendritic cell factor 1(Dcf1) on myelination, using in vitro and in vivo models and found that Dcf1 is essential for normal myelination, motor coordination and balance. Lack of Dcf1 downregulated myelin-associated proteins, such as myelin basic protein (MBP), myelin associated glycoprotein (MAG), and 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampus and corpus callosum of Dcf1-null mice, as a result, the myelin sheath of these mice became thinner. Transmission electron microscopy revealed hypomyelination in Dcf1-deficient mice. Motor coordination and balance tests confirmed impaired neurological function in Dcf1-null mice. Gain-of-function analysis via In utero electroporation showed that hypomyelination could be rescued by re-expression of Dcf1 in Dcf1-null mouse brain. Dcf1-null mice exhibited a phenotype similar to that of cuprizone-induced demyelinated mice, thereby supporting the finding of hypomyelination caused by Dcf1 knockout. Mechanistically, we further revealed that insufficient Dcf1 leads to hyperactivation of the Wnt/β-catenin signaling pathway. Our work describes the role of Dcf1 in maintaining normal myelination, and this could help improve the current understanding of hypomyelination and its pathogenesis.
髓鞘形成对于实现神经功能至关重要。少突胶质细胞发育不全导致多种神经疾病。然而，对于少突胶质细胞发育不全的发生机制知之甚少。在这里，我们使用体外和体内模型研究了树突细胞因子 1（Dcf1）对髓鞘形成的影响，结果发现 Dcf1 对于正常的髓鞘形成、运动协调和平衡是必需的。Dcf1 缺失下调了海马体和胼胝体中髓鞘相关蛋白，如髓鞘碱性蛋白（MBP）、髓鞘相关糖蛋白（MAG）和 2'，3'-环核苷酸 3'-磷酸二酯酶（CNPase），导致这些小鼠的髓鞘变薄。透射电子显微镜显示 Dcf1 缺陷小鼠存在少突胶质细胞发育不全。运动协调和平衡测试证实 Dcf1 缺失小鼠的神经功能受损。通过体内电穿孔的功能获得分析表明，在 Dcf1 缺失小鼠脑中重新表达 Dcf1 可以挽救少突胶质细胞发育不全。Dcf1 缺失小鼠表现出与杯状病毒诱导的脱髓鞘小鼠相似的表型，从而支持了 Dcf1 敲除导致少突胶质细胞发育不全的发现。从机制上讲，我们进一步揭示了 Dcf1 的不足会导致 Wnt/β-catenin 信号通路的过度激活。我们的工作描述了 Dcf1 在维持正常髓鞘形成中的作用，这有助于提高对少突胶质细胞发育不全及其发病机制的认识。
