Oscillatory cortical forces promote three dimensional cell intercalations that shape the murine mandibular arch

Nat Commun. 2019 Apr 12;10(1):1703. doi: 10.1038/s41467-019-09540-z.


Multiple vertebrate embryonic structures such as organ primordia are composed of confluent cells. Although mechanisms that shape tissue sheets are increasingly understood, those which shape a volume of cells remain obscure. Here we show that 3D mesenchymal cell intercalations are essential to shape the mandibular arch of the mouse embryo. Using a genetically encoded vinculin tension sensor that we knock-in to the mouse genome, we show that cortical force oscillations promote these intercalations. Genetic loss- and gain-of-function approaches show that Wnt5a functions as a spatial cue to coordinate cell polarity and cytoskeletal oscillation. These processes diminish tissue rigidity and help cells to overcome the energy barrier to intercalation. YAP/TAZ and PIEZO1 serve as downstream effectors of Wnt5a-mediated actomyosin polarity and cytosolic calcium transients that orient and drive mesenchymal cell intercalations. These findings advance our understanding of how developmental pathways regulate biophysical properties and forces to shape a solid organ primordium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton
  • Actomyosin / metabolism
  • Animals
  • Calcium / metabolism
  • Cell Cycle
  • Cell Polarity*
  • Cytoskeleton / physiology*
  • Cytosol / metabolism
  • Elasticity
  • Epithelial Cells / metabolism
  • Green Fluorescent Proteins / metabolism
  • Mandible / embryology*
  • Mandible / physiology*
  • Mice
  • Mutation
  • Oscillometry
  • Signal Transduction
  • Stress, Mechanical
  • Vinculin / metabolism
  • Viscosity
  • Wnt-5a Protein / physiology*


  • Wnt-5a Protein
  • Wnt5a protein, mouse
  • Vinculin
  • Green Fluorescent Proteins
  • Actomyosin
  • Calcium