Wnt/β-Catenin and Fgf Signaling Control Collective Cell Migration by Restricting Chemokine Receptor Expression
Wnt/β-Catenin and Fgf Signaling Control Collective Cell Migration by Restricting Chemokine Receptor Expression
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DOI：
10.1016/j.devcel.2008.10.002
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发表时间：
2008-11-11
影响因子：
11.8
通讯作者：
Piotrowski, Tatjana
中科院分区：
文献类型：
--
作者：
Aman, Andy;Piotrowski, Tatjana
集体细胞迁移是胚胎形态发生和癌症转移的标志。然而，调节协调细胞迁移的分子机制仍然知之甚少。斑马鱼的侧线原基的迁移对这个问题进行了基因剖析。我们报告说，Wnt/β-连环蛋白和 Fgf 信号传导之间的相互作用通过前导区和尾随区基因表达的差异调节来维持原基极性。前导细胞中的 Wnt/β-连环蛋白信号传导通过两种趋化因子受体 cxcr4b 和 cxcr7b 的差异调节来通知协调迁移。这些发现揭示了一种分子机制，尽管整个细胞群周期性丢失，但迁移组织仍保持稳定、极化的基因表达域。我们的发现对于癌症生物学也具有重要意义。尽管众所周知 Fgf、Wnt/β-连环蛋白和趋化因子信号通路参与癌症进展，但这些研究提供了体内证据表明这些通路在功能上是相关的。
Collective cell migration is a hallmark of embryonic morphogenesis and cancer metastases. However, the molecular mechanisms regulating coordinated cell migration remain poorly understood. A genetic dissection of this problem is afforded by the migrating lateral line primordium of the zebrafish. We report that interactions between Wnt/beta-catenin and Fgf signaling maintain primordium polarity by differential regulation of gene expression in the leading versus the trailing zone. Wnt/beta-catenin signaling in leader cells informs coordinated migration via differential regulation of the two chemokine receptors, cxcr4b and cxcr7b. These findings uncover a molecular mechanism whereby a migrating tissue maintains stable, polarized gene expression domains despite periodic loss of whole groups of cells. Our findings also bear significance for cancer biology. Although the Fgf, Wnt/beta-catenin, and chemokine signaling pathways are well known to be involved in cancer progression, these studies provide in vivo evidence that these pathways are functionally linked.