Abstract
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.
Highlights
A critical milestone of mammalian development is reached when the embryo implants in the maternal uterine tissue [1, 2]
Building on the increasing power of computational modelling in developmental biology [15,16,17,18,19], we examine the influence of trophectoderm morphogenesis on the epiblast
We simulated both tissues’ morphogenesis and showed that the epiblast remodelling into a cup shape and its movement towards the maternal uterine tissue could be explained by trophectoderm morphogenesis
Summary
A critical milestone of mammalian development is reached when the embryo implants in the maternal uterine tissue [1, 2]. We sought to determine theoretically whether hollowing via repulsion at the apical surface of the epiblast rosette was a viable mechanism for lumenogenesis in this tissue.
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