Model of cell fate decision in the early mouse embryo

Embryonic development is a self-organised process during which cells divide, interact and change fate according to a complex gene regulatory network. In the early mouse embryo, the lineage specification of inner cell mass (ICM) cells into epiblast (Epi) and primitive endoderm (PrE) cells is tightly regulated by a gene regulatory network (GRN) and by extracellular signalling. We developed a realistic computational model of this GRN, which was shown to exhibit tri-stability and to account for the self-organized process of specification observed in vivo. The model also sheds light on various observations performed on wild-type or mutant embryos submitted to exogenous treatments that interfere with extracellular signalling. Models of increasing complexity, starting from the single cell level to a population of dividing cells interacting via extracellular signalling, are used to investigate the mechanistic origin of the experimentally observed spatial arrangement of the Epi/PrE cells in a salt-and-pepper pattern. The possible sources of noise, responsible for the initial symmetry breaking in murine early development, will also be discussed.

References

- Bessonnard S., De Mot L., Gonze D., Barriol M., Dennis C., Goldbeter A., Dupont G. and Chazaud C. (2014) Gata6, Nanog and Erk signaling control cell fate in the inner cell mass through a tristable regulatory network. Development 141, 3637-3648.

- De Mot L., Gonze D., Bessonnard S., Chazaud C., Goldbeter A. and Dupont G. (2016) Cell fate specification based on tristability in the inner cell mass of mouse blastocysts. Biophys. J. 110, 710-722.

- Tosenberger A., Gonze D., Bessonnard S., Cohen-Tannoudji M., Chazaud C. and Dupont G. (2017) A multiscale model of early cell lineage specification including cell division. NPJ Systems Biology and Applications, 3: 16.

- Tosenberger A., Gonze D., Chazaud C. and Dupont G. (2019) Computational models for the dynamics of early mouse embryogenesis. Int. J. Dev. Biol. 63, 131.