Sulfatide is a negative regulator of oligodendrocyte differentiation: Development in sulfatide-null mice
Sulfatide is a negative regulator of oligodendrocyte differentiation: Development in sulfatide-null mice
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作者：
Hirahara, Y;Bansal, R;Wada, Y
半乳糖神经酰胺（GalC）及其硫酸化类似物硫脂是神经系统髓磷脂和少突胶质细胞膜的主要半乳糖鞘脂成分。我们之前假设这些半乳糖脂通过充当环境信息的传感器/发射器，在少突胶质细胞末端分化的调节中发挥功能作用。证据有力地支持这一观点。首先，这些分子最初在细胞表面的界面上表达，在这个界面上，少突胶质细胞祖细胞首先进入末梢分化。其次，少突胶质细胞祖细胞暴露于抗galc /-硫脂（RmAb）或抗硫脂（O4）抗体，但不暴露于抗galc （O1）抗体，可导致少突胶质细胞谱系在该界面的可逆阻滞。第三，在脑苷半乳糖转移酶缺失的小鼠（Cgt(-/-)）中，既不能合成半乳糖也不能合成硫脂，少突胶质细胞的末端分化和形态成熟得到增强。在本研究中，我们检测了脑苷硫转移酶缺失小鼠（Cst(-/-)）中少突胶质细胞的分化，这些小鼠缺乏硫脂但表达GalC。我们发现，脑苷硫转移酶mRNA的表达在胚胎脊髓中已经开始，并随着年龄的增长而逐渐增加，在缺乏这种酶的情况下，晚期祖细胞标记POA不会合成，最值得注意的是，在培养和体内，终末分化的少突胶质细胞数量增加了两到三倍，类似于缺乏GalC和硫脂的小鼠。我们得出结论，主要是硫脂，而不是GalC，是负调控少突胶质细胞末梢分化的关键分子。(C) 2003 Wiley-Liss, Inc。
Galactosylceramide (GalC) and its sulfated analogue, sulfatide, are major galactosphingolipid components of myelin and oligodendrocyte plasma membranes in the nervous system. We previously hypothesized that these galactolipids play functional roles in the regulation of oligodendrocyte terminal differentiation by acting as sensors/transmitters of environmental information. Evidence strongly supports this idea. First, these molecules are initially expressed on the cell surface at the interface at which oligodendrocyte progenitors first enter terminal differentiation. Second, exposure of oligodendrocyte progenitors to anti-GalC/-sulfatide (RmAb) or antisulfatide (O4), but not anti-GalC (O1), antibodies leads to the reversible arrest of oligodendrocyte lineage progression at this interface. Third, in cerebroside galactosyl transferase-null mice (Cgt(-/-)) that are unable to synthesize either GalC or sulfatide, terminal differentiation and morphological maturation of oligodendrocytes are enhanced. In the present study, we examined oligodendrocytes differentiation in cerebroside sulfotransferase-null mice (Cst(-/-)) that lack sulfatide but express GalC. We show that cerebroside sulfotransferase mRNA expression begins already in the embryonic spinal cord and progressively increases with age, that the late progenitor marker POA is not synthesized in the absence of this enzyme, and that, most notably, there is a two- to threefold enhancement in the number of terminally differentiated oligodendrocytes both in culture and in vivo, similar to that in mice lacking both GalC and sulfatide. We conclude that primarily sulfatide, rather than GalC, is a key molecule for the negative regulation of oligodendrocyte terminal differentiation. (C) 2003 Wiley-Liss, Inc.