‘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 gradually distinguished. Cells in an outside position keep contact with their environment and remain polarized, whereas inside cells become apolar as they are completely surrounded by others. An outside cell can be divided in two different ways, either symmetrically or asymmetrically. A symmetric or conservative division produces two outside daughter cells, whereas an asymmetric or differantiative division produces one inside and one outside cell. Divisions of the inside cells to produce cells in the outside cannot be found in the literature. (Sashaki et al., 2009).
Two models for the ICM and TE lineage specification
Two different approaches have been historically suggested to explain the mechanism behind the cell fate segregation in mouse preimplantation embryo. Both prevailed after the mosaic model (selective distribution of oocyte determinants) was weakened in mammals (Dalcq, 1957, Mintz, 1965).
The inside-outside model
According to this, the position in the late morula determines fate (Tarkowski and Wroblewska, 1967). ICM differentiation requires an intercellular environment; after the symmetric and asymmetric divisions, cells that will happen to have an inner position will differentiate into ICM....