Heparan Sulfate Proteoglycans Regulate Fgf Signaling and Cell Polarity during Collective Cell Migration

Marina VeneroGalanternik, Ken Kramer, Tatjana Piotrowski

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Collective cell migration is a highly regulated morphogenetic movement during embryonic development and cancer invasion that involves the precise orchestration and integration of cell-autonomous mechanisms and environmental signals. Coordinated lateral line primordium migration is controlled by the regulation of chemokine receptors via compartmentalized Wnt/β-catenin and fibroblast growth factor (Fgf) signaling. Analysis of mutations in two exostosin glycosyltransferase genes ( extl3 and ext2) revealed that loss of heparan sulfate (HS) chains results in a failure of collective cell migration due to enhanced Fgf ligand diffusion and loss of Fgf signal transduction. Consequently, Wnt/β-catenin signaling is activated ectopically, resulting in the subsequent loss of the chemokine receptor cxcr7b. Disruption of HS proteoglycan (HSPG) function induces extensive, random filopodia formation, demonstrating that HSPGs are involved in maintaining cell polarity in collectively migrating cells. The HSPGs themselves are regulated by the Wnt/β-catenin and Fgf pathways and thus are integral components of the regulatory network that coordinates collective cell migration with organ specification and morphogenesis.

Original languageEnglish
Pages (from-to)414-428
Number of pages15
JournalCell Reports
Volume10
Issue number3
DOIs
StatePublished - Jan 20 2015

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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