Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.
Department of Mechanical and Industrial Engineering and Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, M5S 3G8, Canada.
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.
多种脊椎动物胚胎结构，如器官原基，由融合细胞组成。尽管组织片层的形成机制越来越被理解，但形成细胞体积的机制仍不清楚。在这里，我们表明 3D 间充质细胞插入对于塑造小鼠胚胎的下颌弓是必不可少的。我们使用一种遗传编码的 vinculin 张力传感器，将其敲入到小鼠基因组中，表明皮质力振荡促进了这些插入。遗传的失活和功能获得方法表明，Wnt5a 作为一种空间线索，协调细胞极性和细胞骨架振荡。这些过程会降低组织刚性，并帮助细胞克服插入的能量障碍。YAP/TAZ 和 PIEZO1 作为 Wnt5a 介导的肌动球蛋白极性和细胞质钙离子瞬变的下游效应物，定向并驱动间充质细胞插入。这些发现增进了我们对发育途径如何调节生物物理特性和力以塑造固体器官原基的理解。
