A Role in Migration for the αvβ1 Integrin Expressed on Oligodendrocyte Precursors

A Role in Migration for the αvβ1 Integrin Expressed on Oligodendrocyte Precursors
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少突胶质细胞前体表达的 αvβ1 整合素在迁移中的作用

DOI:
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发表时间:
1996
影响因子:
5.3
通讯作者:
C. ffrench
C. ffrench
中科院分区:
医学1区
文献类型:
--
作者:
R. Milner;G. Edwards;C. Streuli;C. ffrench

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中枢神经系统的髓鞘化需要少突胶质细胞前体从心室和心室下区的限制区域迁移到整个中枢神经系统。鉴于细胞-细胞外基质(ECM)相互作用对其他发育系统中细胞迁移的显着影响,我们分析了整合素在少突胶质细胞前体迁移中的作用。我们之前已经表明,少突胶质细胞前体在体外表达有限的整联蛋白,包括α6β1、αvβ1和αvβ3,并且分化与αvβ1的下调和αvβ5的上调有关。使用基于细胞远离含有高密度细胞悬浮液的琼脂糖滴的迁移测定,我们发现RGD肽(阻断αv但不阻断α6整合素)和抗β1抗体阻断星形胶质细胞来源的ECM上的迁移,而抗β3抗体几乎没有作用。这些结果表明αvβ1而不是α6β1在少突胶质细胞前体迁移中发挥作用,并且通过使用区分这两种整合素的封闭单克隆抗体证实了这一点。与其他人的结果一致,我们发现分化的少突胶质细胞失去迁移潜力,并且这种损失的时间与 αvβ1 的下调相关。结合其他人的工作表明αvβ1的ECM配体在中枢神经系统内表达,我们提出该整合素在体内少突胶质细胞前体的迁移中发挥重要作用,并且其在分化过程中的下调可能是调节这些细胞迁移表型的重要因素。
Myelination of the CNS requires the migration of oligodendrocyte precursors throughout the CNS from restricted regions within the ventricular and subventricular zones. In light of the significant effects of cell–extracellular matrix (ECM) interactions on cell migration in other developing systems, we have analyzed the role of integrins in oligodendrocyte precursor migration. We have shown previously that oligodendrocyte precursors in vitroexpress a limited repertoire of integrins, including α6β1, αvβ1, and αvβ3, and that differentiation is associated with downregulation of αvβ1 and upregulation of αvβ5. Using a migration assay based on the movement of cells away from an agarose drop containing a high-density cell suspension, we find that RGD peptides (that block αv but not α6 integrins) and anti-β1 antibodies block migration on an astrocyte-derived ECM, whereas anti-β3 antibodies have little effect. These re- sults suggest that αvβ1 but not α6β1 plays a role in oligodendrocyte precursor migration, and this is confirmed by the use of blocking monoclonal antibodies that distinguish these two integrins. In keeping with the results of others, we find that differentiated oligodendrocytes lose migratory potential and that the timing of this loss correlates with downregulation of αvβ1. Taken together with the work of others showing that ECM ligands for αvβ1 are expressed within the CNS, we propose that this integrin plays a significant role in the migration of oligodendrocyte precursors in vivoand that its downregulation during differentiation could be an important factor regulating the migratory phenotype of these cells.
DOI: --
发表时间: 1990-10
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影响因子: 11.2
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影响因子: --
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DOI: --
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期刊: Development
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