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.
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