Fletcher Alexander G, Cooper Fergus, Baker Ruth E
School of Mathematics and Statistics, University of Sheffield, Sheffield S3 7RH, UK
Bateson Centre, University of Sheffield, Sheffield S10 2TN, UK.
Philos Trans R Soc Lond B Biol Sci. 2017 May 19;372(1720). doi: 10.1098/rstb.2015.0519.
Embryonic epithelia achieve complex morphogenetic movements, including in-plane reshaping, bending and folding, through the coordinated action and rearrangement of individual cells. Technical advances in molecular and live-imaging studies of epithelial dynamics provide a very real opportunity to understand how cell-level processes facilitate these large-scale tissue rearrangements. However, the large datasets that we are now able to generate require careful interpretation. In combination with experimental approaches, computational modelling allows us to challenge and refine our current understanding of epithelial morphogenesis and to explore experimentally intractable questions. To this end, a variety of cell-based modelling approaches have been developed to describe cell-cell mechanical interactions, ranging from vertex and 'finite-element' models that approximate each cell geometrically by a polygon representing the cell's membrane, to immersed boundary and subcellular element models that allow for more arbitrary cell shapes. Here, we review how these models have been used to provide insights into epithelial morphogenesis and describe how such models could help future efforts to decipher the forces and mechanical and biochemical feedbacks that guide cell and tissue-level behaviour. In addition, we discuss current challenges associated with using computational models of morphogenetic processes in a quantitative and predictive way.This article is part of the themed issue 'Systems morphodynamics: understanding the development of tissue hardware'.
胚胎上皮通过单个细胞的协同作用和重排实现复杂的形态发生运动，包括平面内重塑、弯曲和折叠。上皮动力学的分子和实时成像研究方面的技术进步为理解细胞水平的过程如何促进这些大规模组织重排提供了切实的机会。然而，我们现在能够生成的大量数据集需要仔细解读。结合实验方法，计算建模使我们能够质疑和完善我们目前对上皮形态发生的理解，并探索实验上难以处理的问题。为此，已经开发了多种基于细胞的建模方法来描述细胞间的机械相互作用，从通过代表细胞膜的多边形对每个细胞进行几何近似的顶点模型和“有限元”模型，到允许细胞形状更任意的浸入边界模型和亚细胞元件模型。在这里，我们回顾这些模型是如何被用于深入了解上皮形态发生的，并描述这些模型如何有助于未来努力破译引导细胞和组织水平行为的力以及机械和生化反馈。此外，我们讨论了以定量和预测方式使用形态发生过程计算模型所面临的当前挑战。本文是主题为“系统形态动力学：理解组织硬件的发育”的特刊的一部分。
