Institute of Life Sciences, College of Life and Environmental Sciences, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, China.
Glia. 2022 Mar;70(3):590-601. doi: 10.1002/glia.24126. Epub 2021 Dec 10.
Myelin sheathes ensure the rapid conduction of neural impulse and provide nutritional support for neurons. Myelin sheathes are formed by differentiated oligodendrocytes (OLs) in the central nervous system. During OL development, the differentiation of oligodendrocyte progenitor cells (OPCs) into mature OLs is controlled by both positive differentiation factors (drivers) and negative regulatory factors (brakes). Previous studies have suggested Id2 and Id4 as the key negative factors for OL differentiation. However, these conclusions were mainly based on in vitro studies and the reported OL phenotype in Id4 mutants appear to be mild. In this study, we systematically investigated the in vivo function of Id2 and Id4 genes in OL differentiation in their genetic mutants and in embryonic chicken spinal cord. Our results showed that disruption of Id4 has no effect on OL differentiation and maturation, whereas Id2 mutants and Id2/Id4 compound mutants display a mild and transient precocity of OL differentiation. In agreement with these loss-of-function studies, Id2, but not Id4, is weakly expressed in OPCs. Despite their minor roles in OL differentiation, forced expression of Id2 and Id4 in embryonic chicken spinal cords strongly inhibit the differentiation of OPCs. Taken together, our detailed functional and expressional studies strongly suggest that Id2 and Id4 are not the major in vivo repressors of OPC differentiation during animal development, shedding new light on the molecular regulation of early OL development.
髓鞘确保神经冲动的快速传导，并为神经元提供营养支持。髓鞘由中枢神经系统中分化的少突胶质细胞（OLs）形成。在 OL 发育过程中，少突胶质前体细胞（OPCs）分化为成熟 OL 受到正向分化因子（驱动因子）和负向调节因子（刹车）的共同控制。先前的研究表明 Id2 和 Id4 是 OL 分化的关键负向因子。然而，这些结论主要基于体外研究，且 Id4 突变体中报道的 OL 表型似乎较为温和。在这项研究中，我们系统地研究了 Id2 和 Id4 基因在 OL 分化中的体内功能，分别在其基因敲除突变体和鸡胚脊髓中进行了研究。结果显示，Id4 缺失对 OL 分化和成熟没有影响，而 Id2 突变体和 Id2/Id4 双突变体则表现出 OL 分化的轻度和短暂早熟。与这些功能缺失研究一致，Id2 而不是 Id4，在 OPC 中弱表达。尽管它们在 OL 分化中的作用较小，但 Id2 和 Id4 在鸡胚脊髓中的强制表达强烈抑制了 OPC 的分化。综上所述，我们详细的功能和表达研究强烈表明，Id2 和 Id4 不是动物发育过程中 OPC 分化的主要体内抑制因子，为早期 OL 发育的分子调控提供了新的视角。
