Removal of Polysialic Acid Triggers Dispersion of Subventricularly Derived Neuroblasts into Surrounding CNS Tissues
Removal of Polysialic Acid Triggers Dispersion of Subventricularly Derived Neuroblasts into Surrounding CNS Tissues
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DOI：
10.1523/jneurosci.4382-09.2010
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发表时间：
2010-03-17
影响因子：
5.3
通讯作者：
Rutishauser, Urs
中科院分区：
文献类型：
--
作者：
Battista, Daniela;Rutishauser, Urs
室下区产生的细胞产生神经母细胞，沿着头端迁移流（RMS）迁移到嗅球（OB）。这些细胞表达多唾液酸化形式的神经细胞粘附分子 (PSA-NCAM)，并且已被证明可以促进其迁移并抑制 NCAM 诱导的分化。在本研究中，使用 PSA 特异性神经氨酸酶从这些神经母细胞中酶促去除 PSA 不仅会破坏 RMS 的切向迁移和细胞组织，还会导致 BrdU（5-溴-2'-脱氧尿苷）标记的神经母细胞大量分散到周围的大脑区域，包括皮质和纹状体。这些分散的细胞能够分化，其中一些细胞分化为成熟的神经元，并且可能在中枢神经系统损伤的修复中具有潜在的价值。尽管通过 NCAM 基因删除去除 PSA 也会导致 OB 变小和 RMS 肿胀，但细胞不会大量逃离 RMS。这些发现表明，没有 PSA 的 NCAM 的存在在分散过程中发挥了作用，可能是通过诱导与 NCAM 依赖性分化相关的新的迁移模式。
Cells generated in the subventricular zone give rise to neuroblasts that migrate to the olfactory bulb (OB) along the rostral migratory stream (RMS). The polysialylated form of neural cell adhesion molecule (PSA-NCAM) is expressed by these cells, and has been shown to both promote their migration and suppress differentiation induced by NCAM. In the present study, enzymatic removal of PSA from these neuroblasts using PSA-specific endoneuraminidase has been found not only to disrupt the tangential migration and cellular organization of the RMS, but also to cause a massive dispersion of BrdU (5-bromo-2'-deoxyuridine)-labeled neuroblasts into surrounding brain regions, including cortex and striatum. These dispersed cells are capable of differentiation, some into mature neurons, and could potentially be of value in the repair of CNS injury. Although the removal of PSA by genetic deletion of NCAM also results in a smaller OB and a swollen RMS, the cells do not escape the RMS in large numbers. These findings suggest that the presence of NCAM without PSA plays a role in the dispersion process, possibly by inducing a new pattern of migration associated with NCAM-dependent differentiation.