Mechanobiology Institute, National University of Singapore, Singapore 117411.
IInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*Star), Biopolis 138673, Singapore.
Mol Biol Cell. 2017 Dec 1;28(25):3582-3594. doi: 10.1091/mbc.E17-01-0060. Epub 2017 Oct 4.
Organ and tissue formation are complex three-dimensional processes involving cell division, growth, migration, and rearrangement, all of which occur within physically constrained regions. However, analyzing such processes in three dimensions in vivo is challenging. Here, we focus on the process of cellularization in the anterior pole of the early embryo to explore how cells compete for space under geometric constraints. Using microfluidics combined with fluorescence microscopy, we extract quantitative information on the three-dimensional epithelial cell morphology. We observed a cellular membrane rearrangement in which cells exchange neighbors along the apical-basal axis. Such apical-to-basal neighbor exchanges were observed more frequently in the anterior pole than in the embryo trunk. Furthermore, cells within the anterior pole skewed toward the trunk along their long axis relative to the embryo surface, with maximum skew on the ventral side. We constructed a vertex model for cells in a curved environment. We could reproduce the observed cellular skew in both wild-type embryos and embryos with distorted morphology. Further, such modeling showed that cell rearrangements were more likely in ellipsoidal, compared with cylindrical, geometry. Overall, we demonstrate that geometric constraints can influence three-dimensional cell morphology and packing within epithelial tissues.
器官和组织的形成是一个复杂的三维过程,涉及细胞分裂、生长、迁移和重排,所有这些过程都发生在物理受限的区域内。然而,在体内分析这样的三维过程具有挑战性。在这里,我们专注于早期胚胎前极的细胞化过程,以探索在几何约束下细胞如何竞争空间。我们使用微流控技术结合荧光显微镜,提取了关于三维上皮细胞形态的定量信息。我们观察到细胞膜的重排,其中细胞沿着顶端-基底轴与相邻细胞交换位置。在前极中,这种顶端到基底的相邻交换比胚胎主干中更为频繁。此外,前极中的细胞相对于胚胎表面沿其长轴向主干倾斜,在腹侧倾斜度最大。我们构建了一个用于弯曲环境中细胞的顶点模型。我们可以再现观察到的野生型胚胎和形态扭曲胚胎中的细胞倾斜。此外,这种建模表明,与圆柱形相比,细胞重排更可能发生在椭圆形几何中。总的来说,我们证明了几何约束可以影响上皮组织内的三维细胞形态和排列。