The separation of embryonic from extra-embryonic tissues within the inner-cell-mass (ICM) to generate the epiblast (EPI), that will form the new organism, from the primitive endoderm (PE), that will form the yolk sac, is a crucial developmental decision. Here we identify a chromatin modifier, Satb1, with a distinct role in this decision. Satb1 is differentially expressed within 16-cell-stage embryos with higher expression levels in the ICM progenitor cells. Depleting Satb1 increases the number of EPI cells at the expense of PE. This phenotype can be rescued by simultaneous depletion of both Satb1 and Satb2, due to their antagonistic effect on the pluripotency regulator Nanog. Consequently, increasing Satb1 expression leads to differentiation into PE and a decrease in EPI, due to the modulation of expression of several pluripotency- and differentiation-related genes by Satb1. Finally, we show that Satb1 is a downstream target of the Fgf signalling pathway, linking chromatin modification and Fgf signalling. Together, these results identify a role for Satb1 in the lineage choice between pluripotency and differentiation and further our understanding of early embryonic lineage segregation.
- Received August 25, 2016.
- Accepted March 3, 2017.
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