Wnt/beta-catenin and Fgf signaling control collective cell migration by restricting chemokine receptor expression.

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.