'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 mucosa. The cell population that will support this attachment, the trophectoderm (TE), distinguishes itself from the inner cell mass (ICM) at the blastocyst stage, and this separation represents the first lineage restriction. Up to the 8-cell stage, the embryo is characterized by a loose structure, but then compaction follows, a phenomenon mediated by the increase in cell-cell adhesion (tight junctions, increased expression of E-cadherin). Acquisition of a microvillus apical membrane domain, polarization of the cytoplasm, and reorganization of cytoskeletal elements establish apicobasal polarity as blastomeres flatten. (Gilbert, Fleming et al., 2001). Still at this stage, all cells maintain communication with their environment, but after sequential divisions they assume an internal or external position in the late morula. At the 32 cell stage, the cavity of the blastocoel is formed surrounded by the ET which will give rise to the extraembryonic tissues (extraembryonic 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 behind this first differentiation event remain elusive. Elucidation of these mechanisms will contribute to our understanding of early mammalian development and support the field of stem cell biology and induced pluripotency. Conservative and differentiative cell divisions. After the compacted morula, the embryo undergoes two cycles of cleavage, during which the two cell populations become gr...... middle of paper ......(Cdx2, Eomes, Fgfr2) were reexpressed after the introduction of exogenous Sox2. Therefore, Sox2 has been suggested as an early player in the introduction of the TE lineage, but interactions with other transcriptional regulators as well as whether or not maternal Sox2 mRNA actually contributes has yet to be elucidated. From all of the above, it is understood that the transcriptional network that regulates the early cell fate decision is complicated and yet not clearly defined. Recent evidence supports a dual role of Klf5 in lineage specification (Fig. 4). Upregulation of Klf5 is critical for TE development (upstream of Cdx2 and in parallel to Fgf signaling), whereas low levels of Klf5 are required to maintain Oct4 and Nanog expression in the ICM. However, it is necessary to examine the exact mechanism and interactions with other members of the network (Lin., et al., 2010).