The dynamics of extracellular signals coordinate cell lineage decisions during early embryo development. The correct specification of the Inner Cell Mass in Epiblast (Epi), giving rise to the fetus, and Primitive Endoderm (PrE) cells, contributing to the extra-embryonic tissues, ins essential to ensure proper development. Even though the Epi/PrE lineage segregation during early human development is of great importance, its regulation remains understudied due to a lack of suitable in vitro models and human embryo material. In this project, we will block, stimulate, and knock-out pivotal signaling associated transcription factors for early development by signaling modulation and by the CRISPR/Cas9 technology in both human oocytes and naive embryonic stem cells, to characterize molecular networks involved in human Epi/PrE cell lineage commitment, with a specific focus on the role of Wnt/ß-catenin, for which we have obtained preliminary indications. Our results might provide new model systems for in vitro human extraembryonic cell modeling to clarify how extraembryonic lineages coordinate embryo development and how defects in these lineages might contribute to pregnancy failure, which is of great interest for the field of reproductive medicine.