Dynamic filopodia are required for chemokine-dependent intracellular polarization during guided cell migration in vivo

Elife. 2015 Apr 15:4:e05279. doi: 10.7554/eLife.05279.

Abstract

Cell migration and polarization is controlled by signals in the environment. Migrating cells typically form filopodia that extend from the cell surface, but the precise function of these structures in cell polarization and guided migration is poorly understood. Using the in vivo model of zebrafish primordial germ cells for studying chemokine-directed single cell migration, we show that filopodia distribution and their dynamics are dictated by the gradient of the chemokine Cxcl12a. By specifically interfering with filopodia formation, we demonstrate for the first time that these protrusions play an important role in cell polarization by Cxcl12a, as manifested by elevation of intracellular pH and Rac1 activity at the cell front. The establishment of this polarity is at the basis of effective cell migration towards the target. Together, we show that filopodia allow the interpretation of the chemotactic gradient in vivo by directing single-cell polarization in response to the guidance cue.

Keywords: cell migration; chemokine; chemotaxis; developmental biology; germ cell; stem cells; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement*
  • Cell Polarity*
  • Chemokine CXCL12 / metabolism*
  • Embryo, Nonmammalian / metabolism
  • Endocytosis / drug effects
  • Germ Cells / cytology*
  • Germ Cells / metabolism
  • Intracellular Space / metabolism*
  • Models, Biological
  • Pseudopodia / metabolism*
  • Receptors, CXCR4 / metabolism
  • Zebrafish / embryology
  • Zebrafish / metabolism
  • Zebrafish Proteins / metabolism*

Substances

  • CXCR4b protein, zebrafish
  • Chemokine CXCL12
  • Receptors, CXCR4
  • Zebrafish Proteins
  • cxcl12a protein, zebrafish

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.