Acheta Jenica, Hong Jiayue, Jeanette Haley, Brar Simrandeep, Yalamanchili Anish, Feltri M Laura, Manzini M Chiara, Belin Sophie, Poitelon Yannick
Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY, United States.
Departments of Biochemistry and Neurology, Institute for Myelin and Glia Exploration, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, United States.
Front Mol Neurosci. 2022 May 3;15:881571. doi: 10.3389/fnmol.2022.881571. eCollection 2022.
Numerous studies have indicated that myelination is the result of the interplay between extracellular signals and an intricate network of transcription factors. Yet, the identification and characterization of the full repertoire of transcription factors that modulate myelination are still incomplete. CC2D1B is a member of the Lgd/CC2D1 family of proteins highly expressed in myelinating cells in the central and peripheral nervous systems. In addition, the absence of CC2D1B limits myelin formation . Here we propose to delineate the function of CC2D1B in myelinating cells during developmental myelination in the central and peripheral nervous systems.
We used a constitutive knockout mouse model and then performed morphological analyses on semithin sections of sciatic nerves and electron micrographs of optic nerves. We also performed immunohistological studies on coronal brain sections. All analyses were performed at 30 days of age.
In the peripheral nervous system, animals ablated for did not show any myelin thickness difference compared to control animals. In the central nervous system, immunohistological studies did not show any difference in the number of oligodendrocytes or the level of myelin proteins in the cortex, corpus callosum, and striatum. However, optic nerves showed a hypomyelination (0.844 ± 0.022) compared to control animals (0.832 ± 0.016) of large diameter myelinated fibers.
We found that CC2D1B plays a role in developmental myelination in the central nervous system. These results suggest that CC2D1B could contribute to gene regulation during oligodendrocytes myelination in optic nerves.
大量研究表明,髓鞘形成是细胞外信号与复杂转录因子网络相互作用的结果。然而,对调节髓鞘形成的转录因子全部种类的鉴定和表征仍不完整。CC2D1B是Lgd/CC2D1蛋白家族的成员,在中枢和外周神经系统的髓鞘形成细胞中高度表达。此外,CC2D1B的缺失会限制髓鞘形成。在此,我们提议阐明CC2D1B在中枢和外周神经系统发育性髓鞘形成过程中在髓鞘形成细胞中的功能。
我们使用了一种组成型敲除小鼠模型,然后对坐骨神经的半薄切片和视神经的电子显微照片进行形态学分析。我们还对冠状脑切片进行了免疫组织学研究。所有分析均在30日龄时进行。
在外周神经系统中,与对照动物相比,缺失CC2D1B的动物未显示出任何髓鞘厚度差异。在中枢神经系统中,免疫组织学研究未显示皮质、胼胝体和纹状体中少突胶质细胞数量或髓鞘蛋白水平有任何差异。然而,与对照动物(0.832±0.016)相比,视神经显示出大直径有髓纤维的髓鞘形成不足(0.844±0.022)。
我们发现CC2D1B在中枢神经系统的发育性髓鞘形成中起作用。这些结果表明,CC2D1B可能在视神经少突胶质细胞髓鞘形成过程中参与基因调控。