Origins of oligodendrocytes in the cerebellum, whose development is controlled by the transcription factor, Sox9
Origins of oligodendrocytes in the cerebellum, whose development is controlled by the transcription factor, Sox9
复制标题
DOI：
10.1016/j.mod.2016.02.004
复制
发表时间：
2016-05-01
影响因子：
2.6
通讯作者：
Hoshino, Mikio
中科院分区：
文献类型：
--
作者：
Hashimoto, Ryoya;Hori, Kei;Hoshino, Mikio
少突胶质细胞（中枢神经系统（CNS）中形成髓磷脂的神经胶质细胞）的发育是长期进行的。少突胶质细胞祖细胞（OPC）的特化在发育早期就开始，而它们的终末分化发生在胚胎晚期和出生后时期。然而，对于小脑中的少突胶质细胞，其发育起源和控制这些不同步骤的分子机制仍不清楚。通过体内命运图谱和免疫组织化学分析，我们获得的证据表明，小脑中的大多数少突胶质细胞起源于腹侧菱核1（r1）中表达Olig2的神经上皮结构域，而约6%的小脑少突胶质细胞是在小脑脑室区产生的。此外，为了阐明调节其发育的分子决定因素，我们分析了通过 Cre/loxP 重组系统从小脑、腹侧 r1 和尾部中脑特异性消除转录因子 Sox9 的小鼠。这导致 Sox9 缺陷小鼠中 OPC 的产生延迟以及这些细胞随后的发育异常。此外，我们观察到 OPC 增殖发生改变，导致少突胶质细胞数量减少，并伴有分化减弱和细胞凋亡率增加。使用少突胶质细胞富集培养物进行的体外测定的结果进一步支持了我们在体内实验中的观察结果。这些数据表明，Sox9 通过调节少突胶质细胞的生成、增殖、分化和存活的时间，参与小脑少突胶质细胞的发育。 (C) 2016 Elsevier Ireland Ltd. 保留所有权利。
Development of oligodendrocytes, myelin-forming glia in the central nervous system (CNS), proceeds on a protracted schedule. Specification of oligodendrocyte progenitor cells (OPCs) begins early in development, whereas their terminal differentiation occurs at late embryonic and postnatal periods. However, for oligodendrocytes in the cerebellum, the developmental origins and the molecular machinery to control these distinct steps remain unclear. By in vivo fate mapping and immunohistochemical analyses, we obtained evidence that the majority of oligodendrocytes in the cerebellum originate from the Olig2-expressing neuroepithelial domain in the ventral rhombomere 1 (r1), while about 6% of cerebellar oligodendrocytes are produced in the cerebellar ventricular zone. Furthermore, to elucidate the molecular determinants that regulate their development, we analyzed mice in which the transcription factor Sox9 was specifically ablated from the cerebellum, ventral r1 and caudal midbrain by means of the Cre/loxP recombination system. This resulted in a delay in the birth of OPCs and subsequent developmental aberrations in these cells in the Sox9-deficient mice. In addition, we observed altered proliferation of OPCs, resulting in a decrease in oligodendrocyte numbers that accompanied an attenuation of the differentiation and an increased rate of apoptosis. Results from in vitro assays using oligodendrocyte-enriched cultures further supported our observations from in vivo experiments. These data suggest that Sox9 participates in the development of oligodendrocytes in the cerebellum, by regulating the timing of their generation, proliferation, differentiation and survival. (C) 2016 Elsevier Ireland Ltd. All rights reserved.