To elucidate the biological roles of Bptf-containing complexes we have generated embryonic stem cell and mouse mutants for Bptf [15]. Our studies show that Bptf mutant phenotypes begin to manifest just after implantation stage, and mutant embryos are completely reabsorbed by embryonic day (E) 8.5. Genetic and molecular analysis in embryonic stem cells and the mouse suggest a role for Bptf in the development of visceral endoderm (VE) of the early mammalian embryo. We propose that Bptf is required for the development of the VE, and more importantly the distal visceral endoderm (DVE), in part through regulating cellular proliferation, the expression of homeobox-containing transcription factors and pathways regulated by the Smad transcription factors, a major conduit for cell signaling in development. These findings suggest a model in which the activities of Bptf-containing complexes, likely the NURF remodeling complex, regulate cell proliferation and embryonic development and therefore are essential in the post-implantation embryo.