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

Abstract

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.

Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk

“…In our study, decreased YAP nuclear localization was observed in Piezo1-deficient mice, resulting in impaired collagen II and IX expression which leads to increased bone resorption. YAP/TAZ and PIEZO1 serve as downstream effectors of Wnt5a-mediated actomyosin polarity and cytosolic calcium transients that orient and drive three-dimensional cell intercalations that shape the murine mandibular arch 42 . It remains to be investigated whether Wnt5a will regulate the PIEZO1-YAP-collagen pathway in mechanotransduction mediated bone remodeling.…”

Magnetic Micromanipulation for In Vivo Measurement of Stiffness Heterogeneity and Anisotropy in the Mouse Mandibular Arch

“…The precision of these implications has been improving as we move from hypothetical assertions [ 3 ] to relative measurements [ 4 ], to absolute measurements [ 5 – 7 ] coupled with theory [ 7 – 9 ]. With regard to forces, the magnitude and directional bias, or polarity, of cytoskeletal contractions are relevant to how cells rearrange and bias the shapes of tissue sheets and bulk mesenchymal structures [ 5 , 10 – 14 ]. The magnitudes and spatial distributions of tissue properties also influence the growth and form of tissues by mechanisms that are being elucidated [ 9 , 11 , 14 ].…”

“…With regard to forces, the magnitude and directional bias, or polarity, of cytoskeletal contractions are relevant to how cells rearrange and bias the shapes of tissue sheets and bulk mesenchymal structures [ 5 , 10 – 14 ]. The magnitudes and spatial distributions of tissue properties also influence the growth and form of tissues by mechanisms that are being elucidated [ 9 , 11 , 14 ]. Outstanding questions are whether and how tissue properties regulate anisotropic processes such as convergent extension.…”

Role of Hippo-YAP1/TAZ pathway and its crosstalk in cardiac biology

“…Interestingly, a growing body of evidence indicates that Wnt proteins can activate YAP1/TAZ, independent of Wnt/β-catenin signaling in many cell lines [47][48][49][50][51]. An alternative Wnt pathway has been promulgated, consisting of Wnt, FZD/ROR, Ga12/13, Rho GTPases, LATS1/2, and YAP1/TAZ, wherein YAP1 and TAZ are the key downstream transcription cofactors [49].…”

“…Wnt3a activates the Wnt-YAP1/TAZ pathway to maintain the pluripotency of bovine trophoblast stem cells (TSCs) [50]. The Wnt5a-induced YAP1/TAZ activation mediates cell polarity and formation of organ primordia [47]. Wnt-activated YAP1 regulates rostral and caudal brain tissue identity and affects neural tissue from human-induced pluripotent stem cells (hiPSCs) [51].…”