Antagonistic activities of Rho and Rac GTPases underlie the transition from neural crest delamination to migration

Irit Shoval, Chaya Kalcheim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Background: Neural crest progenitors arise as epithelial cells and then undergo a transition into mesenchyme that generates motility. Previously, we showed that active Rho maintains crest cells in the epithelial conformation by keeping stress fibers and membrane-bound N-cadherin. Results: While Rho disappears from cell membranes upon delamination, active Rac1 becomes apparent in lamellipodia of mesenchymal cells. Loss of Rac1 function at trunk levels inhibited NC migration but did not prevent cell emigration that is associated with N-cadherin downregulation and G1/S transition. Furthermore, inhibition of Rho stimulated premature Rac1 activity and consequent formation of lamellipodia, leading to NC migration. To examine whether timely migration influences cell fate, Rac1 activity was transiently inhibited to delay dispersion of early NC cells that generate neural derivatives, and its activity was restored by the time of melanoblast migration. Even if confronted with a melanocytic environment, late-dispersing progenitors colonized sensory ganglia where they generated neurons and glia. Conclusions: In the context of crest delamination and migration, activities of Rho and Rac are differential, sequential, and antagonistic. Furthermore, transient inhibition of Rac1 that delays the onset of crest dispersion raises the possibility that the fate of trunk neural progenitors might be restricted prior to migration.

Original languageAmerican English
Pages (from-to)1155-1168
Number of pages14
JournalDevelopmental Dynamics
Volume241
Issue number7
DOIs
StatePublished - Jul 2012

Keywords

  • Actin
  • Avian embryo
  • C3 transferase
  • Cadherin
  • Cell fate
  • Epithelial to mesenchymal transition
  • FoxD3
  • Rho kinase
  • Sox9

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