Little is known about the molecular mechanisms controlling the earliest cellular differentiation events of the mammalian embryo. Pluripotent embryonic stem (ES) cell lines, derived from cells of the inner cell mass of the blastocyst, are an important experimental system that can be used to study the differentiation of the mammalian embryo into its earliest recognizable tissue lineages. For instance, experiments performed in ES cells demonstrate the essential role of the homeobox-containing geneOct3/4in the totipotent cells of the preimplantation embryo (1 ). When two alleles ofOct3/4are mutated in ES cells,Oct3/4-null cells lose their pluripotency and differentiate into only trophoblast cells. In contrast, whenOct3/4is overexpressed in ES cells, spontaneous differentiation occurs and a variety of mesoderm-specific and extraembryonic endoderm-specific genes are expressed. Similar results have been obtained from in vivo experiments usingOct3/4knock-out mice (2 ). Mouse preimplantation embryos, with two null alleles ofOct3/4, develop into blastocysts containing primary trophoblast giant cells but lacking inner cell mass cells. Taken together, the in vitro and in vivo studies ofOct3/4function indicate thatOct3/4is one of the key factors regulating the differentiation of totipotent cells of the preimplantation embryo.
