Formation of the Trophectoderm Lineage

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‘Formation of the trophectoderm lineage. The first cell fate decision in mammalian development’.

The crucial outcome of the 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 earliest lineage restriction. Up to the 8-cell stage, the embryo is characterized by a loose structure, but then compaction follows, a phenomenon mediated by increased cell-cell adhesion (tight junctions, increased E-cadherin expression). Acquisition of a microvillus apical membrane domain, polarization of the cytoplasm and reorganization of cytoskeleton elements establish apicobasal polarity while blastomeres become flattened. (Gilbert, Fleming et al., 2001). Still at this stage, all cells maintain communication with their environment, but after sequential divisions they either take an inner or outer position in the late morula. By 32-cell stage, the blastocoel cavity is formed surrounded by the TE that will give rise to extraembryonic tissues (extraembryonic ectoderm and the trophoblast). Attached to one side of the TE epithelium, the ICM will form the embryo proper and nontrophoblast extraembryonic tissues. The molecular mechanisms behind this first differentiation event remain elusive. Clarification of these mechanisms will contribute to our understanding of early mammalian development and will support the field of stem cell biology and induced pluripotency.

Conservative versus differantiative cell divisions.

After the compacted morula, the embryo undergoes two rounds of cleavage, during which the two cell populations become gr...

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...(Cdx2, Eomes, Fgfr2) were re-expressed after the introduction of exogenous Sox2. Therefore, Sox2 was suggested as an early player in the introduction of the TE lineage, but interactions with the other transcriptional regulators as well as actual contribution or not of maternal Sox2 mRNA still need to be illuminated.

From all 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 of Klf5 in lineage specification (Fig 4). Upregulation of Klf5 is critical for TE development (upstream of Cdx2 and in parallel to Fgf signal), whereas low levels of Klf5 are needed to maintain the expression of Oct4 and Nanog in the ICM. Still, the exact mechanism and the interactions with other members of the network need to be examined (Lin., et al., 2010).

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