Computational modelling unveils how epiblast remodelling and positioning rely on trophectoderm morphogenesis during mouse implantation

PLoS One. 2021 Jul 28;16(7):e0254763. doi: 10.1371/journal.pone.0254763. eCollection 2021.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Proliferation
  • Embryo Implantation
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Embryonic Development
  • Endoderm / cytology*
  • Endoderm / metabolism
  • Germ Layers / cytology*
  • Germ Layers / metabolism
  • Mice
  • Models, Biological*

Grants and funding

This work has received funding from the European Union’s Horizon 2020 Research and Innovation Programme ImageInLife under the Marie Sklodowska-Curie grant agreement No.~721537. We are also grateful for the support of the NSF-Simons Center for Quantitative Biology at Northwestern University (awards Simons Foundation/SFARI 597491-RWC and the National Science Foundation 1764421).