The early development of mammalian embryos is largely devoted to formation of a pluripotent cell population, known as the epiblast (Epi), and its segregation from two extra-embryonic tissues essential for embryo survival and patterning in utero. The epiblast is the progenitor tissue of most somatic cells and source of embryonic stem (ES) cells. Early development culminates in the formation of the blastocyst stage.
Blastocyst development offers a simple but relevant model for investigating the coordination of cell lineage commitment and morphogenesis. Blastocyst formation is characterised by two binary cell fate decisions. The first leads to the specification of the trophectoderm (TE) and inner cell mass (ICM). In the second, ICM cells will become either pluripotent epiblast (Epi) or primitive endoderm (PrE).
The blastocyst is a unique stage of embryo from which stem cells representing each of the constituent cell lineages can be derived directly from embryos. Embryonic stem (ES) cells represent the epiblast (Epi); trophoblast stem (TS) cells represent the trophectoderm (TE), and extra-embrynoc endoderm (XEN) stem cells represent the primitive endoderm (PrE). These embryo-derived stem cells can be propagated, differentiated and interconverted in vitro.
The focus of our work is to elucidate the mechanisms driving cell lineage specification and segregation leading to the formation of a blastocyst stage embryo, using the mouse as an experimental model. To acheive this goal we are exploiting various approaches, including live imaging, mouse genetics, embryo manipulations and single-cell expression profiling, as well as embryo-derived stem cells.