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.
Aman
Andy
A
Department of Neurobiology and Anatomy, University of Utah School of Medicine, 401 MREB, 20N Medical Drive, Salt Lake City, UT 84132, USA.
Piotrowski
Tatjana
T
D000818:Animals; D002465:Cell Movement; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D009369:Neoplasms / Q000378:metabolism; D054387:Receptors, CXCR / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
C519524:CXCR7 protein, zebrafish; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D005346:Fibroblast Growth Factors