17-P011 Oct3/4 activates Cdx1 to terminate pluripotency at the onset of gastrulation

Gastrulation is characterized by the differentiation of pluripotent cells to generate the germ layers, morphogenetic movements, a decrease in cell proliferation and establishment of the embryonic axes. We show by Cdx1 knock-down that it functions as a regulator of the onset of gastrulation in agreement with its early expression. In a microarray-based approach to search for Cdx1 targets, we identified the Xenopus Oct3/4-like genes, Oct60, Oct25 and Oct91, as regulated by Cdx1. All three Oct3/4-like genes function as gatekeepers of pluripotency and are expressed in pluripotent cells in the embryo. In gainand loss-of-function experiments we show that Cdx1 negatively regulates the Oct3/4-like genes during late blastula and early gastrula stages. These results place Cdx1 at the crossroads between pluripotency and germ layer formation. We further characterized the cross-regulatory network between these genes showing, that during late blastula the Oct3/4-like genes positively regulate Cdx1, and with the onset of gastrulation they become negative regulators of Cdx1 transcription. A model is proposed where the Cdx1 and the Oct3/4 genes establish a cross-regulatory network that eventually leads to the loss of pluripotency and permits the onset of gastrulation and early differentiation events.