Centre for Advanced Computational Science (CfACS), Manchester Metropolitan University, Manchester, United Kingdom.
NSF-Simons Center for Quantitative Biology, Northwestern University, Evanston, Illinois, United States of America.
PLoS One. 2021 Jul 28;16(7):e0254763. doi: 10.1371/journal.pone.0254763. eCollection 2021.
Understanding the processes by which the mammalian embryo implants in the maternal uterus is a long-standing challenge in embryology. New insights into this morphogenetic event could be of great importance in helping, for example, to reduce human infertility. During implantation the blastocyst, composed of epiblast, trophectoderm and primitive endoderm, undergoes significant remodelling from an oval ball to an egg cylinder. A main feature of this transformation is symmetry breaking and reshaping of the epiblast into a "cup". Based on previous studies, we hypothesise that this event is the result of mechanical constraints originating from the trophectoderm, which is also significantly transformed during this process. In order to investigate this hypothesis we propose MG# (MechanoGenetic Sharp), an original computational model of biomechanics able to reproduce key cell shape changes and tissue level behaviours in silico. With this model, we simulate epiblast and trophectoderm morphogenesis during implantation. First, our results uphold experimental findings that repulsion at the apical surface of the epiblast is essential to drive lumenogenesis. Then, we provide new theoretical evidence that trophectoderm morphogenesis indeed can dictate the cup shape of the epiblast and fosters its movement towards the uterine tissue. Our results offer novel mechanical insights into mouse peri-implantation and highlight the usefulness of agent-based modelling methods in the study of embryogenesis.
理解哺乳动物胚胎在母体子宫内着床的过程是胚胎学中的一个长期挑战。对这一形态发生事件的新见解可能对帮助减少人类不孕等问题具有重要意义。在着床过程中，由上胚层、滋养外胚层和原始内胚层组成的囊胚经历了从椭圆形球到卵圆柱的显著重塑。这种转变的一个主要特征是上胚层的对称性破坏和重塑成“杯状”。基于先前的研究，我们假设这一事件是滋养外胚层起源的机械约束的结果，在这个过程中，滋养外胚层也发生了显著的转化。为了验证这一假设，我们提出了 MG#（机械遗传锐化），这是一种原始的生物力学计算模型，能够在计算机上再现关键的细胞形状变化和组织水平行为。利用该模型，我们模拟了着床过程中上胚层和滋养外胚层的形态发生。首先，我们的结果支持了实验发现，即上胚层顶端表面的排斥对于驱动腔形成是至关重要的。然后，我们提供了新的理论证据，表明滋养外胚层的形态发生确实可以决定上胚层的杯状，并促进其向子宫组织移动。我们的结果为小鼠着床前后提供了新的力学见解，并强调了基于代理的建模方法在胚胎发生研究中的有用性。
