The first two lineages to differentiate from a pluripotent cell population during mammalian development are the extraembryonic trophectoderm (TE) and primitive endoderm (PrE). While the mechanisms of TE specification have been extensively studied, segregation of PrE and the pluripotent epiblast (EPI) has received comparatively little attention. To gain a mechanistic understanding and determine the precise sequence of events and that leads to the specification and segregation of EPI and PrE lineages within the mouse blastocyst we are adopting a live imaging approach combined with the analysis of mouse mutants.
Embryonic Stem (ES) cells are pluripotent cells derived from epiblast (EPI) of the mammalian balstocyst stage embryo that have the capacity to give rise to any fetal tissue. The ES genome can be modified at base pair resolution. We are interested in the mechanisms regulating the developmental potential of primitive endoderm-derived XEN cells. Current work exploits live imaging tools and mouse genetics to investigate ES and XEN cell maintenance, differentiation and intercoversion, including the transcription factors and signaling pathways regulating their self-renewal and directed differentiation.