Weliky M, Oster G
Group in Neurobiology, University of California, Berkeley 94720.
Development. 1990 Jun;109(2):373-86. doi: 10.1242/dev.109.2.373.
Many morphogenetic processes are accomplished by coordinated cell rearrangements. These rearrangements are accompanied by substantial shifts in the neighbor relationships between cells. Here we propose a model for studying morphogenesis in epithelial sheets by directed cell neighbor change. Our model describes cell rearrangements by accounting for the balance of forces between neighboring cells within an epithelium. Cell rearrangement and cell shape changes occur when these forces are not in mechanical equilibrium. We will show that cell rearrangement within the epidermal enveloping layer (EVL) of the teleost fish Fundulus during epiboly can be explained solely in terms of the balance of forces generated among constituent epithelial cells. Within a cell, we account for circumferential elastic forces and the force generated by hydrostatic and osmotic pressure. The model treats epithelial cells as two-dimensional polygons where the mechanical forces are applied to the polygonal nodes. A cell node protrudes or contracts when the nodal forces are not in mechanical equilibrium. In an epithelial sheet, adjacent cells share common boundary nodes; in this way, mechanical force is transmitted from cell to cell, mimicking junctional coupling. These junctional nodes can slide, and nodes may appear or disappear, so that the number of polygonal sides is variable. Computer graphics allows us to compare numerical simulations of the model with time-lapse cinemicroscopy of cell rearrangements in the living embryo, and data obtained from fixed and silver stained embryos. By manipulating the mechanical properties of the model cells we can study the conditions necessary to reproduce normal cell behavior during Fundulus epiboly. We find that simple stress relaxation is sufficient to account for cell rearrangements among interior cells of the EVL when they are isotropically contractile. Experimental observations show that the number of EVL marginal cells continuously decreases throughout epiboly. In order for the simulation to reproduce this behavior, cells at the EVL boundary must generate protrusive forces rather than contractile tension forces. Therefore, the simulation results suggest that the mechanical properties of EVL marginal cells at their leading edge must be quite different from EVL interior cells.
许多形态发生过程是通过协调的细胞重排来完成的。这些重排伴随着细胞间邻接关系的显著变化。在此，我们提出了一个通过定向细胞邻接变化来研究上皮片层形态发生的模型。我们的模型通过考虑上皮组织内相邻细胞间力的平衡来描述细胞重排。当这些力处于非力学平衡状态时，细胞重排和细胞形状变化就会发生。我们将证明，在鳉鱼胚胎外包过程中，硬骨鱼Fundulus表皮包被层（EVL）内的细胞重排可以仅根据组成上皮细胞间产生的力的平衡来解释。在一个细胞内，则考虑周向弹力以及静水压力和渗透压产生的力。该模型将上皮细胞视为二维多边形，其中机械力作用于多边形节点。当节点力处于非力学平衡状态时，细胞节点会突出或收缩。在上皮片中，相邻细胞共享共同的边界节点；这样，机械力就从一个细胞传递到另一个细胞，模拟连接耦合情况。这些连接节点可以滑动，节点也可能出现或消失，从而使多边形边的数量可变。计算机图形学使我们能够将模型的数值模拟与活胚胎中细胞重排过程的延时电影显微镜观察结果以及从固定和银染胚胎获得的数据进行比较。通过操纵模型细胞的力学特性，我们可以研究在Fundulus胚胎外包过程中重现正常细胞行为所需的条件。我们发现，当EVL内部细胞呈各向同性收缩时，简单的应力松弛足以解释这些细胞间的重排。实验观察表明，在整个外包过程中，EVL边缘细胞的数量持续减少。为了使模拟重现这种行为，EVL边界处的细胞必须产生突出力而非收缩张力。因此，模拟结果表明，EVL边缘细胞前缘的力学特性必定与EVL内部细胞有很大不同。
