Identification of Tmem10/Opalin as an oligodendrocyte enriched gene using expression profiling combined with genetic cell ablation.

Identification of Tmem10/Opalin as an oligodendrocyte enriched gene using expression profiling combined with genetic cell ablation.
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DOI:
10.1002/glia.20688
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发表时间:
2008-08-15
期刊:
影响因子:
6.2
通讯作者:
Peles, Elior
Peles, Elior
中科院分区:
医学1区
文献类型:
--
作者:
Golan, Neev;Adamsky, Konstantin;Kartvelishvily, Elena;Brockschnieder, Damln;Moebius, Wiebke;Spiegel, Ivo;Roth, Alejandro D.;Thomson, Christine E.;Rechavi, Gideon;Peles, Elior

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少突胶质细胞在轴突周围形成致密髓鞘的绝缘多层结构,这允许动作电位的有效和快速传播。然而,很少有人知道的分子机制,在髓鞘形成的发病和维持期间的髓鞘在成人。在这里,我们使用基因细胞消融方法结合Affyssin基因芯片微阵列,以确定一些少突胶质细胞富集的基因,可能在髓鞘形成中发挥关键作用。我们使用这种方法克隆的“寡基因”之一是Tmem 10/Opalin,它编码一种新的跨膜糖蛋白。原位杂交和RT-PCR分析表明,Tmem 10是选择性表达的少突胶质细胞,其表达诱导其分化过程中。发育免疫荧光分析表明,Tmem 10开始表达在白色物质轨道的小脑和胼胝体的髓鞘形成开始后,出现其他髓鞘基因,如MBP。与脊髓和大脑相反,在髓鞘形成的雪旺细胞中没有检测到Tmem 10,表明它是CNS特异性髓鞘蛋白。在成熟的少突胶质细胞中,Tmem 10存在于细胞索马和突起,以及沿着有髓鞘的节间,在那里它偶尔集中在旁阳极。在髓鞘形成的脊髓培养物中,在髓鞘形成开始之前与下面的轴突对齐的MBP阳性细胞过程中检测到Tmem 10。这些结果表明Tmem 10在少突胶质细胞分化和CNS髓鞘形成中的可能作用。
Oligodendrocytes form an insulating multilamellar structure of compact myelin around axons, which allows efficient and rapid propagation of action potentials. However, little is known about the molecular mechanisms operating at the onset of myelination and during maintenance of the myelin sheath in the adult. Here we use a genetic cell ablation approach combined with Affymetrix GeneChip microarrays to identify a number of oligodendrocyte-enriched genes that may play a key role in myelination. One of the “oligogenes” we cloned using this approach is Tmem10/Opalin, which encodes for a novel transmembrane glycoprotein. In situ hybridization and RT-PCR analysis revealed that Tmem10 is selectively expressed by oligodendrocytes and that its expression is induced during their differentiation. Developmental immunofluorescence analysis demonstrated that Tmem10 starts to be expressed in the white matter tracks of the cerebellum and the corpus callosum at the onset of myelination after the appearance of other myelin genes such as MBP. In contrast to the spinal cord and brain, Tmem10 was not detected in myelinating Schwann cells, indicating that it is a CNS-specific myelin protein. In mature oligodendrocytes, Tmem10 was present at the cell soma and processes, as well as along myelinated internodes, where it was occasionally concentrated at the paranodes. In myelinating spinal cord cultures, Tmem10 was detected in MBP-positive cellular processes that were aligned with underlying axons before myelination commenced. These results suggest a possible role of Tmem10 in oligodendrocyte differentiation and CNS myelination.
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期刊: GENESIS
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