Genetic control of cell fate decisions in the developing mouse embryo

Understanding the logic of transcriptional networks that control temporally and spatially correct patterns of gene expression required to establish cell identity is the central challenge in developmental biology. My research has provided fundamental insights into regulatory events during axis patterning and cell lineage specification in the developing mouse embryo. A consistent theme is that a handful of so-termed “master regulators” govern the transcriptional networks that coordinately regulate cell type specific target gene expression in diverse tissue contexts. The proposed experiments are interconnected by the cross-cutting question: how do the master transcription factors Eomes, a T-box family member and the zinc finger transcriptional repressor Blimp1/Prdm1 control cell fate decisions? The first goal of my proposal is to define the underlying transcriptional networks and time window(s) when Eomes-dependent progenitors of the node, midline and DE become lineage restricted during gastrulation. We also aim to characterize Eomes requirements during specification of the hemogenic endothelium giving rise to the first wave of primitive blood. Secondly we will further characterize Blimp1 functional contributions, define upstream signalling pathways governing Blimp1 tissue-specific expression and identify its key downstream transcriptional targets in trophoblast sub-populations and decidual cells at the maternal-fetal interface.