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1型星形胶质细胞和少突胶质细胞-2型星形胶质细胞神经胶质祖细胞向不同分子迁移。

Type 1 astrocytes and oligodendrocyte-type 2 astrocyte glial progenitors migrate toward distinct molecules.

作者信息

Armstrong R C, Harvath L, Dubois-Dalcq M E

机构信息

Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892.

出版信息

J Neurosci Res. 1990 Nov;27(3):400-7. doi: 10.1002/jnr.490270319.

Abstract

During central nervous system (CNS) development, glial precursors proliferate in subventricular zones and then migrate throughout the CNS to adopt their final destinations and differentiate into various types of mature glial cells. Although several growth factors promoting the proliferation and/or differentiation of glial precursors have been identified, very little is known about the nature of signals that guide glial cell migration in the CNS. Therefore, we have investigated whether polypeptide growth factors and/or extracellular matrix molecules may mediate the migration of two major glial cell types, type 1 astrocytes and oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells. We show that, in a microchemotaxis chamber assay, type 1 astrocytes move toward laminin and complement-derived C5a. Astrocyte migration toward laminin is inhibited by a laminin-specific pentapeptide, YIGSR-NH2. In contrast, O-2A progenitors migrate toward platelet-derived growth factor (PDGF), which also functions as a mitogen for these cells. Using a new method to simultaneously assay migration and DNA synthesis, we also demonstrate that O-2A progenitors can migrate toward PDGF even when DNA replication is inhibited with an antimitotic agent. Thus, migration of different types of glial cells can be induced in vitro by specific signaling molecules, which are present in the developing brain and may stimulate migration of glial cells prior to CNS myelination.

摘要

在中枢神经系统(CNS)发育过程中,神经胶质前体细胞在脑室下区增殖,然后迁移至整个中枢神经系统,到达其最终位置并分化为各种类型的成熟神经胶质细胞。尽管已经鉴定出几种促进神经胶质前体细胞增殖和/或分化的生长因子,但对于引导中枢神经系统中神经胶质细胞迁移的信号本质却知之甚少。因此,我们研究了多肽生长因子和/或细胞外基质分子是否可能介导两种主要神经胶质细胞类型(1型星形胶质细胞和少突胶质细胞-2型星形胶质细胞(O-2A)祖细胞)的迁移。我们发现,在微趋化性室分析中,1型星形胶质细胞向层粘连蛋白和补体衍生的C5a移动。星形胶质细胞向层粘连蛋白的迁移受到层粘连蛋白特异性五肽YIGSR-NH2的抑制。相反,O-2A祖细胞向血小板衍生生长因子(PDGF)迁移,PDGF对这些细胞也起促有丝分裂原的作用。使用一种同时检测迁移和DNA合成的新方法,我们还证明即使使用抗有丝分裂剂抑制DNA复制,O-2A祖细胞仍可向PDGF迁移。因此,发育中的大脑中存在的特定信号分子可在体外诱导不同类型神经胶质细胞的迁移,并且这些信号分子可能在中枢神经系统髓鞘形成之前刺激神经胶质细胞的迁移。

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