Depletion of Suds3 reveals an essential role in early lineage specification

► Suds3 is required in vivo for specification of trophoblast and primitive endoderm. ► Suds3 is required proper ICM/Epiblast gene expression and Sox2-FGF4-ERK signaling. ► Sox2 localizes to future ICM cell nuclei prior to Oct4 restriction.