Computational models for the dynamics of early mouse embryogenesis

Abstract

Early embryonic development, from the zygote to the blastocyst, is a paradigm of a dynamic, self-organised process. It involves gene expression, mechanical interactions between cells, cell division and inter- and intracellular signalling. Imaging and transcriptomic data have significantly improved our understanding of early embryogenesis in mammals. However, they also reveal a great level of complexity. How the genetic, mechanical, and regulatory processes interact to ensure reproducible development is thus much investigated by computational modelling, which allows a dissection of the mechanisms controlling cell fate decisions. In this review, we discuss the main types of modelling approaches that have been used to investigate the dynamics of preimplantation mammalian development. We also discuss the insights provided by modelling into our understanding of the specification processes leading to the three types of cells in the embryo 4.5 days after fertilization: the trophectoderm, the epiblast and the primitive endoderm.

Growth-factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development

“…Existing models of cell fate specification in the blastocyst have combined a switch mediated by transcription factors (Huang et al, 2007) with growth factor feedback (Bessonnard et al, 2014;Nissen et al, 2017;Schröter et al, 2015;Tosenberger et al, 2017) (reviewed in Simon et al, 2018;Tosenberger et al, 2019). However, the lack of experimental evidence for direct mutual inhibition between the transcription factors NANOG and GATA6 in the embryo, and the non-cell autonomous nature of this cell fate decision (Figure 1), suggest that intercellular feedback alone could drive this process.…”

Effects of In Utero Exposure to Perfluorooctane Sulfonate on Placental Functions

“…In the experiment, at the time of animal mating, there were no statistical differences in the weights of female mice of the control and treatment groups. PFOS exposure started on the date of blastocyst formation (GD4.5) when the attachment of the blastocyst occurred . The placental is then developed by the appearance of amnion, chorion, and allantois at GD6.5, followed by the chorioallantoic fusion which forms the chorionic trophoblast layer to form the placental labyrinth at GD 10–14.5 and support the exchange of nutrients, gases, and wastes between the mother and fetus .…”

Growth factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development

“…Existing models of cell fate specification in the blastocyst have combined a switch mediated by transcription factors (Huang et al, 2007) with growth factor feedback (Bessonnard et al, 2014;Nissen et al, 2017;Schröter et al, 2015;Tosenberger et al, 2017) (reviewed in Simon et al, 2018Tosenberger et al, 2019). However, the lack of experimental evidence for direct mutual inhibition between the transcription factors NANOG and GATA6 in the embryo, and the non-cell autonomous nature of this cell fate decision ( Fig.…”