The first cell-fate decision of mouse preimplantation embryo development: integrating cell position and polarity

Abstract

During the first cell-fate decision of mouse preimplantation embryo development, a population of outer-residing polar cells is segregated from a second population of inner apolar cells to form two distinct cell lineages: the trophectoderm and the inner cell mass (ICM), respectively. Historically, two models have been proposed to explain how the initial differences between these two cell populations originate and ultimately define them as the two stated early blastocyst stage cell lineages. The 'positional' model proposes that cells acquire distinct fates based on differences in their relative position within the developing embryo, while the 'polarity' model proposes that the differences driving the lineage segregation arise as a consequence of the differential inheritance of factors, which exhibit polarized subcellular localizations, upon asymmetric cell divisions. Although these two models have traditionally been considered separately, a growing body of evidence, collected over recent years, suggests the existence of a large degree of compatibility. Accordingly, the main aim of this review is to summarize the major historical and more contemporarily identified events that define the first cell-fate decision and to place them in the context of both the originally proposed positional and polarity models, thus highlighting their functional complementarity in describing distinct aspects of the developmental programme underpinning the first cell-fate decision in mouse embryogenesis.

Keywords: cell positioning and polarity; cell-fate; preimplantation mouse embryo.

Figure 1.

The preimplantation period of mouse embryo development. (a) The temporal sequence of events throughout preimplantation mouse embryo development with relevant embryonic stages and cell lineages generated as a result of the first and the second cell-fate decisions. (b) Orientation of the embryonic–abembryonic axis in the late blastocyst stage embryo (E4.5). Note the position of mural and polar trophectoderm at abembryonic and embryonic poles of the embryo, respectively. (c) A non-compacted 8-cell-stage embryo undergoing the first morphogenetic event (compaction) to develop into an early morula-stage embryo. Concomitantly, intracellular polarization is established as exemplified by the apical (green), and basolateral (purple) membrane domains of individual blastomeres.

Figure 2.

The classical ‘polarity’ and ‘positional’ models proposed to explain the first cell-fate decision. (a) A schematic representation of the ‘polarity’ model showing that the differences required to set the trophectoderm (TE) and the ICM cell lineages apart arise as a result of an asymmetric partitioning of polarized subcellular components between daughter cells (e.g. differential inheritance of apical and basolateral membrane domains) upon asymmetric cell division; solid green and purple lines, respectively, mark the apical and basolateral membrane domains, while the dashed black line marks the cell cleavage plane. (b) A schematic representation of the ‘positional’ model showing that the differences required for the segregation of the TE and the ICM cell lineages originate in the differential extent of cell-to-cell contact between individual blastomeres, corresponding to their relative position in the embryo; the sites of the cell-to-cell contact are highlighted with two parallel black lines, reminiscent of adherens junctions.

Figure 3.

The possible outcomes for intracellular polarity and position following ‘perfect’ symmetric, ‘perfect’ asymmetric and oblique/‘imperfect’ asymmetric cell cleavage divisions. (a) A ‘perfect’ symmetric cell division (with the cleavage plane parallel with the apical–basolateral axis of polarity) produces two identical polar outer-residing daughter cells. (b) A ‘perfect’ asymmetric cell division (with the cleavage plane orthogonal to the apical–basolateral axis of polarity) produces a polar outer-residing and an apolar inner daughter cell. (c) An ‘imperfect’ asymmetric cell division (with the cleavage plane oblique to the apical–basolateral axis of polarity, at an angle that implies partitioning of the apical domain) produces two daughter cells that each inherit a certain but uneven portion of the apical domain in addition to an outside position immediately upon cell division. Note that in (a–c) solid green and purple lines, respectively, mark the apical and basolateral membrane domains, while dashed black lines mark cell cleavage planes.

Figure 4.

An encompassing ‘polarity-dependent cell-positioning’ model of the first cell-fate decision in preimplantation mouse embryo development. A schematic representation of the ‘polarity-dependent cell-positioning’ model showing that, based upon the orientation of a cell division (either at the 8-cell stage or in outer blastomeres at the 16-cell stage) with respect to the apical–basolateral polarity axis, daughter cells are generated with differing extents of apical–basolateral polarity and can acquire different initial positions (i.e. are subjected to different degrees of cell-to-cell contact) in the embryo. Simultaneous inheritance of a functional apical domain and an outer position upon cell division allows a cell to maintain its position, prevent Hippo-signalling pathway activation and subsequently acquire trophectoderm (TE) fate; an alternative scenario in which a daughter cell inherits an extensive amount of the apical domain and an inner position upon cell division is not observable during preimplantation mouse embryo development (see schematic ablated by a cross). In contrast, an apolar cell that initially inherits the inner position within the embryo (completely surrounded by other cells) is prevented from repolarizing and due to resultant Hippo-signalling pathway activation acquires the ICM fate. Finally, the fate of a daughter cell that inherits a small portion of the apical domain, or no apical domain whatsoever, and initially resides on the outside of the embryo, is conditional upon the balance between polarity (that acts to prevent cell internalization) and actomyosin contractility (that drives cell internalization). The absence of cell-to-cell contact at the contactless domain provides an opportunity for the cell to repolarize/enhance polarity, in order to overcome the internalizing forces of actomyosin contractility. Thus, in cases where polarity prevails over contractility (P > C), the cell retains the outside position and suppressed Hippo-signalling pathway, and contributes to the TE. However, if the forces of actomyosin contractility prevail over the inhibitory influence of polarity (P < C), a cell becomes internalized and the opportunity to repolarize is lost. Consequently, the Hippo-signalling pathway becomes active and the cell acquires an ICM fate. Note that solid green and purple lines, respectively, mark the apical and basolateral membrane domains, while dashed black lines mark the potential cleavage planes. In addition, the sites of cell-to-cell contact (indicative of the cell position in the embryo) are marked with two parallel black lines.