In vivo confinement promotes collective migration of neural crest cells

J Cell Biol. 2016 Jun 6;213(5):543-55. doi: 10.1083/jcb.201602083. Epub 2016 May 30.

Abstract

Collective cell migration is fundamental throughout development and in many diseases. Spatial confinement using micropatterns has been shown to promote collective cell migration in vitro, but its effect in vivo remains unclear. Combining computational and experimental approaches, we show that the in vivo collective migration of neural crest cells (NCCs) depends on such confinement. We demonstrate that confinement may be imposed by the spatiotemporal distribution of a nonpermissive substrate provided by versican, an extracellular matrix molecule previously proposed to have contrasting roles: barrier or promoter of NCC migration. We resolve the controversy by demonstrating that versican works as an inhibitor of NCC migration and also acts as a guiding cue by forming exclusionary boundaries. Our model predicts an optimal number of cells in a given confinement width to allow for directional migration. This optimum coincides with the width of neural crest migratory streams analyzed across different species, proposing an explanation for the highly conserved nature of NCC streams during development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Aggregation / drug effects
  • Cell Movement* / drug effects
  • Computer Simulation
  • Female
  • Fibronectins / metabolism
  • Models, Biological
  • Neural Crest / cytology*
  • Neural Crest / drug effects
  • Time-Lapse Imaging
  • Versicans / pharmacology
  • Xenopus

Substances

  • Fibronectins
  • Versicans