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.
Highlights
Multiple vertebrate embryonic structures such as organ primordia are composed of confluent cells
The cellular and biophysical basis of these malformations are not clear, it has been shown that mutant WNT5A may exhibit neomorphic properties that affect cell polarity and migration in a chick model of human Robinow syndrome[42]
Using a random walk model, we found that the cumulative distribution function (CDF) of persistence time exhibited a greater slope for cells in the middle compared to those in the distal region, indicating the former are more directionally consistent over time (Supplementary Fig. 2G–J, Supplementary Movie 9, 10)
Summary
Multiple vertebrate embryonic structures such as organ primordia are composed of confluent cells. Changes in the viscoelastic properties of tissue are associated with, and may partly drive, morphogenetic movements[12,13,14,15], the relationship between cellular and tissue scale properties remains incompletely understood and may be context-dependent Multiple organ primordia such as the branchial arches and limb buds are composed of an internal bulk layer of mesenchyme. In models of multilayered vertebrate tissues such as the frog gastrula, mechanisms of morphogenesis include amoeboid endodermal cell movements[16] and mesodermal cell intercalations through junctional remodelling, though the latter takes place in a sheet-like manner[17,18] Another example is elongation of the rodlike skeletal anlage in the vertebrate limb that is attributable to a highly structured columnar arrangement of chondrocytes embedded within abundant extracellular matrix and to oriented rearrangement of nascent daughter cells[19,20]. The cellular and biophysical basis of these malformations are not clear, it has been shown that mutant WNT5A may exhibit neomorphic properties that affect cell polarity and migration in a chick model of human Robinow syndrome[42]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
