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

Hirotaka Tao | Min Zhu | Kimberly Lau | Owen K W Whitley | Mohammad Samani | Xiao Xiao | Xiao Xiao Chen | Noah A Hahn | Weifan Liu | Megan Valencia | Min Wu | Xian Wang | Kelli D Fenelon | Clarissa C Pasiliao | Di Hu | Jinchun Wu | Shoshana Spring | James Ferguson | Edith P Karuna | R Mark Henkelman | Alexander Dunn | Huaxiong Huang | Hsin-Yi Henry Ho | Radhika Atit | Sidhartha Goyal | Yu Sun | Sevan Hopyan
Nature communications | 2019

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.

Pubmed ID: 30979871

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NIDCR NIH HHS, United States
    Id: R01 DE018470
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM119574

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