FIGURE 5 | Models of blastocyst formation.

a | The cleavage driven hypothesis states that subtle differences between cells — arising as the cells divide — give them a bias towards particular developmental paths. These differences might be advantages in progressing through the cell cycle or differences in cell polarity. In an extension to this model, one cell (dark blue) is shown as having the tendency, from the 8-cell stage onwards, to undergo predominantly symmetric divisions, which give rise to outside cells.These cells might have weaker connections to inside cells, as they generate fewer inner cell mass (ICM) cells to which they will be connected, creating a preferred site at which fluid could accumulate to form the cavity⁷⁹. Inside cells are shown in yellow, outside cells in blue and red lines indicate sister cells. Arrows indicate expansion as the cavity expands. b | Flattening the zygote can change the orientation of the embryonic–abembryonic axis with respect to the animal–vegetal axis but not with respect to the first cleavage⁴⁵. The resulting 2-cell blastomeres tended to populate the respective embryonic and abembryonic blastocyst parts. The cavity could either develop where attachments between cells are the weakest, which has been suggested to reflect the cleavage patterns (as in a), or be 'forced' to one end of the long axis as a result of increasing pressure. c |An alternative model⁷¹ in which the cavity fluid accumulates in response to pressure that is created by force on the zona as embryos are elongated — 2-cell embryos were compressed to show that the cavity formed at one end of the long axis. Although lineages were not traced, and therefore the outcome could not be related to the first cleavage, this model proposes that the cavity formation shows no relationship to the cleavage pattern. PB, polar body.

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