Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects, Ministry of Education, Sichuan University, Chengdu 610041, China.
Rev Neurosci. 2019 Jul 26;30(6):625-638. doi: 10.1515/revneuro-2018-0090.
White matter injury (WMI) prevents the normal development of myelination, leading to central nervous system myelination disorders and the production of chronic sequelae associated with WMI, such as chronic dyskinesia, cognitive impairment and cerebral palsy. This results in a large emotional and socioeconomic burden. Decreased myelination in preterm infant WMI is associated with the delayed development or destruction of oligodendrocyte (OL) lineage cells, particularly oligodendrocyte precursor cells (OPCs). The development of cells from the OL lineage involves the migration, proliferation and different stages of OL differentiation, finally leading to myelination. A series of complex intrinsic, extrinsic and epigenetic factors regulate the OPC cell cycle withdrawal, OL lineage progression and myelination. We focus on the inhibitor of DNA binding 2 (ID2), because it is widely involved in the different stages of OL differentiation and genesis. ID2 is a key transcription factor for the normal development of OL lineage cells, and the pathogenesis of WMI is closely linked with OL developmental disorders. ID4, another family member of the IDs protein, also plays a similar role in OL differentiation and genesis. ID2 and ID4 belong to the helix-loop-helix family; they lack the DNA-binding sequences and inhibit oligodendrogenesis and OPC differentiation. In this review, we mainly discuss the roles of ID2 in OL development, especially during OPC differentiation, and summarize the ID2-mediated intracellular and extracellular signaling pathways that regulate these processes. We also discuss ID4 in relation to bone morphogenetic protein signaling and oligodendrogenesis. It is likely that these developmental mechanisms are also involved in the myelin repair or remyelination in human neurological diseases.
脑白质损伤（WMI）可妨碍髓鞘正常形成，导致中枢神经系统髓鞘形成障碍，并产生与 WMI 相关的慢性后遗症，如慢性运动障碍、认知障碍和脑瘫等，从而带来巨大的情感和社会经济负担。早产儿 WMI 中的髓鞘减少与少突胶质细胞（OL）谱系细胞，特别是少突胶质前体细胞（OPC）的发育延迟或破坏有关。OL 谱系细胞的发育涉及细胞迁移、增殖和不同阶段的 OL 分化，最终导致髓鞘形成。一系列复杂的内在、外在和表观遗传因素调节 OPC 细胞周期退出、OL 谱系进展和髓鞘形成。我们专注于 DNA 结合抑制因子 2（ID2），因为它广泛参与 OL 分化和发生的不同阶段。ID2 是 OL 谱系细胞正常发育的关键转录因子，WMI 的发病机制与 OL 发育障碍密切相关。ID4 是 IDs 蛋白的另一个家族成员，在 OL 分化和发生中也发挥类似作用。ID2 和 ID4 属于螺旋-环-螺旋家族；它们缺乏 DNA 结合序列，抑制少突胶质发生和 OPC 分化。在这篇综述中，我们主要讨论 ID2 在 OL 发育中的作用，特别是在 OPC 分化过程中的作用，并总结 ID2 介导的调节这些过程的细胞内和细胞外信号通路。我们还讨论了 ID4 与骨形态发生蛋白信号和少突胶质发生的关系。这些发育机制可能也参与了人类神经疾病中的髓鞘修复或再髓鞘化。
