TY - JOUR T1 - An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells JF - bioRxiv DO - 10.1101/000653 SP - 000653 AU - J. Trott AU - D. A. Turner AU - P. Hayward AU - S. Borchia AU - A. M. Mateus AU - P. Rué AU - A. Martinez Arias Y1 - 2013/01/01 UR - http://biorxiv.org/content/early/2013/11/21/000653.abstract N2 - Embryonic Stem cells derived from the epiblast tissue of the mammalian blastocyst retain the capability to differentiate into any adult cell type and are able self-renew indefinitely under appropriate culture conditions. Despite the large amount of knowledge that we have accumulated to date about the regulation and control of self-renewal, efficient directed differentiation into specific tissues remains a pending subject. In this work, we have analysed in a systematic manner the interaction between the dynamics of loss of pluripotency and Activin/Nodal, BMP4 and Wnt signalling in fate assignment during the early stages of differentiation of mouse ES cells in culture. During the initial period of differentiation cells exit from pluripotency and enter an Epi-like state. After this transient period and under the influence of a gradient of Activin/nodal or BMP signalling a decision between differentiating into neuroectoderm and contributing to Primitive Streak fates is made. Whilst cells emerge from pluripotency with an intrinsic competence for the neuroectoderm fate, the competence for Primitive Streak occurs over a discrete temporal window. Surprisingly Wnt signalling aids both fates in a context dependent manner. ER -