Redistribution of Adhesive Forces through Src/FAK Drives Contact Inhibition of Locomotion in Neural Crest

Dev Cell. 2018 Jun 4;45(5):565-579.e3. doi: 10.1016/j.devcel.2018.05.003.

Abstract

Contact inhibition of locomotion is defined as the behavior of cells to cease migrating in their former direction after colliding with another cell. It has been implicated in multiple developmental processes and its absence has been linked to cancer invasion. Cellular forces are thought to govern this process; however, the exact role of traction through cell-matrix adhesions and tension through cell-cell adhesions during contact inhibition of locomotion remains unknown. Here we use neural crest cells to address this and show that cell-matrix adhesions are rapidly disassembled at the contact between two cells upon collision. This disassembly is dependent upon the formation of N-cadherin-based cell-cell adhesions and driven by Src and FAK activity. We demonstrate that the loss of cell-matrix adhesions near the contact leads to a buildup of tension across the cell-cell contact, a step that is essential to drive cell-cell separation after collision.

Keywords: FAK; N-cadherin; Src; collective cell migration; extracellular matrix; focal adhesion; focal contacts; intercellular tension; neural crest; traction forces.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Adhesion / physiology*
  • Cell Movement / physiology*
  • Cells, Cultured
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / physiology*
  • Focal Adhesion Protein-Tyrosine Kinases / genetics
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Neural Crest / cytology
  • Neural Crest / physiology*
  • Phosphorylation
  • Xenopus laevis / embryology
  • Xenopus laevis / physiology*
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism*

Substances

  • Cadherins
  • Focal Adhesion Protein-Tyrosine Kinases
  • src-Family Kinases