Webb A, Clark P, Skepper J, Compston A, Wood A
Neurology Unit, University of Cambridge, Addenbrooke's Hospital, UK.
J Cell Sci. 1995 Aug;108 ( Pt 8):2747-60. doi: 10.1242/jcs.108.8.2747.
Oligodendrocyte progenitors arise in subventricular zones and migrate extensively during development before differentiating into mature oligodendrocytes, which myelinate nerve tracts in the central nervous system. We have used microfabricated substrata, containing periodic patterns of contours similar to those of central nervous system axons to assess the influence in vitro of substratum topography on oligodendrocytes isolated from 7 day rat optic nerve. Antiganglioside antibody A2B5 positive oligodendrocyte-type 2 astrocyte progenitors, and galactocerebroside positive and myelin basic protein positive oligodendrocytes, were highly aligned by surface contours as small as 100 nm depth and 260 nm repeat spacing. Rat optic nerve astrocytes also aligned on surface contours, but rat hippocampal and cerebellar neurons were unresponsive. Oligodendrocytes demonstrated enhanced parallel extension of their processes on narrow repeating topography in an arrangement similar to that found in the intact optic nerve. This is in marked contrast to the phenotype displayed by this cell type on planar substrata. Neither oligodendrocytes nor oligodendrocyte-type 2 astrocyte progenitors showed high-order F-actin cytoskeletal networks; thus their alignment on gratings is unlikely to result from deformation of actin cables and focal contacts. In contrast, aligned astrocytes showed striking arrangements of actin stress fibres. These results establish glial cells as potentially the most topographically sensitive cell types within the central nervous system. Furthermore, the topographical pattern inducing maximal alignment of oligodendrocyte lineage cells corresponds to the diameters of single axons within the 7 day optic nerve. Thus the migration of oligodendrocyte-type 2 astrocyte progenitors and axonal ensheathment by oligodendrocytes may be guided by axonal topography within the developing nerve.
少突胶质前体细胞起源于脑室下区，在发育过程中广泛迁移，然后分化为成熟的少突胶质细胞，这些细胞会在中枢神经系统中形成神经纤维髓鞘。我们使用了微加工基质，其包含与中枢神经系统轴突轮廓相似的周期性图案，以评估体外基质拓扑结构对从7日龄大鼠视神经分离出的少突胶质细胞的影响。抗神经节苷脂抗体A2B5阳性的少突胶质细胞 - 2型星形胶质前体细胞，以及半乳糖脑苷脂阳性和髓鞘碱性蛋白阳性的少突胶质细胞，会被深度小至100nm且重复间距为260nm的表面轮廓高度排列。大鼠视神经星形胶质细胞也会在表面轮廓上排列，但大鼠海马和小脑神经元无反应。少突胶质细胞在狭窄的重复拓扑结构上表现出其突起的平行延伸增强，其排列方式与完整视神经中的相似。这与该细胞类型在平面基质上显示的表型形成鲜明对比。少突胶质细胞和少突胶质细胞 - 2型星形胶质前体细胞均未显示高阶F - 肌动蛋白细胞骨架网络；因此它们在光栅上的排列不太可能是由肌动蛋白电缆和粘着斑的变形导致的。相比之下，排列的星形胶质细胞显示出明显的肌动蛋白应力纤维排列。这些结果表明神经胶质细胞可能是中枢神经系统中对拓扑结构最敏感的细胞类型。此外，诱导少突胶质细胞谱系细胞最大排列的拓扑模式与7日龄视神经内单个轴突的直径相对应。因此，少突胶质细胞 - 2型星形胶质前体细胞的迁移和少突胶质细胞对轴突的包裹可能受发育中神经内轴突拓扑结构的引导。
