Genetic control of cell fate decisions in the developing mouse embryo. (360G-Wellcome-102811_Z_13_Z)

My previous research has provided fundamental insights into TGFb/Bmp growth signalling pathways controlling axis patterning and cell lineage specification in the developing mouse embryo. A consistent theme emerging from our recent work is that a handful of so-termed master regulators acting downstream of TGFb/Bmp signals govern the transcriptional networks that co-ordinately regulate cell type specific target gene expression in diverse tissue contexts. Understanding the logic and circuitry b y which these transcriptional networks control temporally and spatially restricted expression of the effectors that correctly establish cell identity is the central challenge in developmental biology. Over the next decade my work will investigate how transcription factors acting downstream of TGFb/Bmp signals execute diverse functions according to their cellular context in different cell lineages and tissues. My interests focus on the formation of mesodermal and endodermal cell lineages du ring gastrulation and their subsequent diversification during organogenesis, and also encompass development of the placenta and post-natal re-programming of the gut endoderm. The proposed experiments are interconnected by the cross-cutting question as to how the two master transcription factors Eomes, a T-box gene and the zinc finger repressor Blimp1/Prdm1 function upstream in the hierarchy that regulates cell fate decisions. We will gain new insights into how cells integrate their differen tiation status within the local signalling environment to respond appropriately and execute diverse functional programmes in partnership with their neighbours to generate a complex organism.