Signalling mechanisms regulating differentiation progression in mouse embryonic stem cells and embryos. (360G-Wellcome-086458_Z_08_A)

The proposed experiments investigate signalling mechanisms that promote differentiation progression of pluripotent cells and analogous cell populations in the developing mouse embryo Specifically, we plan to address the involvement of retinoid signalling in the acquisition of somatic cell fates in these contexts. We will: i) define early epiblast-like cell populations cultured in vitro with respect to the developing embryonic epiblast; ii) determine the role and requirement for retinoid signalling for differentiation of Epistem cells and mouse embryonic epiblast; iii) employ a genome-wide microarray screen to identify mediators of RA or FGFR inhibition-driver differentiation of Epistem/day1 ES cells and validate and functionally test a key subset of FGFR regulated genes in these cells and in the embryo.