Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration

Elife. 2019 Jan 16;8:e42093. doi: 10.7554/eLife.42093.

Abstract

Non-canonical Wnt signaling plays a central role for coordinated cell polarization and directed migration in metazoan development. While spatiotemporally restricted activation of non-canonical Wnt-signaling drives cell polarization in epithelial tissues, it remains unclear whether such instructive activity is also critical for directed mesenchymal cell migration. Here, we developed a light-activated version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm (prechordal plate, ppl) cell migration within the zebrafish gastrula. We found that Fz7 signaling is required for ppl cell protrusion formation and migration and that spatiotemporally restricted ectopic activation is capable of redirecting their migration. Finally, we show that uniform activation of Fz7 signaling in ppl cells fully rescues defective directed cell migration in fz7 mutant embryos. Together, our findings reveal that in contrast to the situation in epithelial cells, non-canonical Wnt signaling functions permissively rather than instructively in directed mesenchymal cell migration during gastrulation.

Keywords: Wnt; cell biology; cell migration; developmental biology; optogenetics; planar cell polarity; polarity; protrusion formation; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Movement / radiation effects*
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / radiation effects
  • Endoderm / cytology*
  • Light*
  • Mesoderm / cytology*
  • Mutation / genetics
  • Phenotype
  • Receptors, Cell Surface / metabolism*
  • Stem Cells / cytology
  • Stem Cells / radiation effects
  • Wnt Signaling Pathway / radiation effects*
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish Proteins / metabolism*

Substances

  • Receptors, Cell Surface
  • Zebrafish Proteins
  • fzd7a protein, zebrafish