'Formation of the trophectoderm lineage. The first cell fate decision in mammalian development. The crucial outcome of early mammalian development is the attachment of the embryo to the uterine lining. The cell population that will support this attachment, the trophectoderm (TE), is distinguished from the inner cell mass (ICM) at the blastocyst stage and this separation represents the first restriction of the lineage. Until the 8-cell stage, the embryo is characterized by a loose structure, but then compaction ensues, a phenomenon mediated by increased cell-cell adhesion (tight junctions, increased E-cadherin expression). Acquisition of an apical membrane domain of microvilli, polarization of the cytoplasm, and reorganization of cytoskeletal elements establish apicobasal polarity while blastomeres flatten. (Gilbert, Fleming et al., 2001). Still at this stage, all cells maintain communication with their environment, but after sequential divisions they take an internal or external position in the late morula. At the 32-cell stage, the blastocoel cavity forms surrounded by TEs which will give rise to extra-embryonic tissues (extra-embryonic ectoderm and trophoblast). Attached to one side of the TE epithelium, the ICM will form the embryo proper and non-trophoblastic extraembryonic tissues. The molecular mechanisms underlying this first differentiation event remain elusive. Clarification of these mechanisms will contribute to our understanding of early mammalian development and support the field of stem cell biology and induced pluripotency. Conservative or differential cell divisions. After the morula compacts, the embryo undergoes two rounds of cleavage, during which both cell populations become gr...... middle of paper ......(Cdx2, Eomes, Fgfr2) were reexpressed after the introduction of exogenous Sox2. Therefore, Sox2 has been suggested as one of the first players in the introduction of TE lineage, but the interactions with other transcriptional regulators as well as whether or not maternal Sox2 mRNA actually contributes still need to be clarified. From all of the above, it is understood that the transcriptional network regulating the first cell fate decision is complicated and yet not clearly defined. Recent evidence supports a dual role for Klf5 in lineage specification (Fig. 4). Upregulation of Klf5 is essential for TE development (upstream of Cdx2 and in parallel with the Fgf signal), whereas low levels of Klf5 are required to maintain Oct4 and Nanog expression in the ICM. Nevertheless, the exact mechanism and interactions with other network members need to be examined (Lin., et al.., 2010).