Regulation and dynamics of progressive cell fate transitions and morphogenesis during development of the early mouse embryo.

We wish to understand the key molecular events that lead a cell from its pluripotent state to differentiation focusing upon the sequential events of the very first cell fate decisions leading to formation of the mouse blastocyst. We will analyse differential gene expression in the changing transcriptional landscape as these decisions are taken and will identify the functions of genes key for mediating these developmental processes. In complementary studies we will relate these molecular events t o the developmental properties of cells that are associated with polarisation and the timing of cell internalization. To understand how the body plan is set up we have developed a new in vitro culture system that permits the first 4D imaging of events that normally take place hidden from view within the mother. We will apply computer assisted cell tracking of living embryos cultured in this way to characterize the dynamics of morphogenesis as the body axis first forms. The accessibility of such embryos will permit us to study how events at this critical stage are regulated by disrupting key signaling pathways, introducing exogenous stem cells, or by ectopically positioning signaling molecules.