Versican V0 and V1 guide migratory neural crest cells
Versican V0 and V1 guide migratory neural crest cells
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DOI：
10.1074/jbc.m510834200
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发表时间：
2006-04-28
影响因子：
4.8
通讯作者：
Zimmermann, DR
中科院分区：
文献类型：
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作者：
Dutt, S;Kléber, M;Zimmermann, DR
我们先前显示了硫酸软骨素蛋白聚糖多功能蛋白聚糖V0和V1在屏障组织中的选择性表达，所述屏障组织在胚胎干发育期间阻碍神经嵴细胞的迁移（Landolt，R. M.，沃恩湖，Winterhalter，K. H、和Zimmermann，D. R.（1995）Development 212，2303 - 2312）。为了测试这些亚型在指导过程中的积极参与，我们现在已经建立了协议，以分离完整的多功能蛋白聚糖V0和V1的数量足以进行功能实验。使用条纹选择试验，我们表明，无论是多功能蛋白聚糖V0/V1或V1的混合物的纯制剂单独强烈抑制迁移的多能Sox 10/p75 NTR双阳性早期神经嵴干细胞纤连蛋白通过干扰细胞基质粘附。我们表明，这种抑制在很大程度上是核心糖蛋白依赖性的，因为糖胺聚糖链的完全去除对抑制能力只有很小的影响。我们的研究结果支持的概念，多功能蛋白聚糖变体V0和V1的行为，可能与其他抑制分子，如聚集蛋白聚糖和肝配蛋白，在指导迁移流的神经嵴细胞到其适当的靶组织。
We previously showed the selective expression of the chondroitin sulfate proteoglycans versican V0 and V1 in barrier tissues that impede the migration of neural crest cells during embryonic trunk development (Landolt, R. M., Vaughan, L., Winterhalter, K. H., and Zimmermann, D. R. ( 1995) Development 212, 2303 - 2312). To test for an active involvement of these isoforms in the guidance process, we have now established protocols to isolate intact versican V0 and V1 in quantities sufficient for functional experiments. Using stripe choice assays, we demonstrate that pure preparations of either a mixture of versican V0/V1 or V1 alone strongly inhibit the migration of multipotent Sox10/p75NTR double-positive early neural crest stem cells on fibronectin by interfering with cell-substrate adhesion. We show that this inhibition is largely core glycoprotein-dependent, as the complete removal of the glycosaminoglycan chains has only a minor effect on the inhibitory capacity. Our findings support the notion that versican variants V0 and V1 act, possibly in concert with other inhibitory molecules such as aggrecan and ephrins, in directing the migratory streams of neural crest cells to their appropriate target tissues.