Fig. 8. Decision-making in the early mouse embryo. The prevailing models (upper panels) over the past 20-30 years have acknowledged a differentiation event that discriminates ICM (white) from trophectoderm (pale green) lineages. In the ‘inside-outside’ hypothesis Tarkowski and Wroblewska (Tarkowski and Wroblewska, 1967) proposed that the daughter cells that are directed inwards upon the 4th cell division (8- to 16-cell stage) encounter an environment that leads them to become ICM. However, in the ‘polarisation’ hypothesis, Johnson and Ziomek (Johnson and Ziomek, 1981) argued that blastomeres are polarised at the eight-cell stage, so the 4th and subsequent divisions can generate daughters with different cytoplasmic and cortical components, hence differing fates. The ‘cleavage-driven’ hypothesis incorporates elements of these earlier models for formation of the ICM and the trophectoderm, but recognises the novel findings that the first cleavage divides the embryo into its future embryonic (red) and abembryonic (blue) parts. The progeny of the two-cell blastomere that has a division advantage at the second cleavage tend to occupy the embryonic part, while the progeny of the later dividing blastomere tend to occupy the abembryonic part of the blastocyst. The blastocyst cavity is often slightly tilted from the embryonic-abembryonic clonal border. This ‘cleavage-driven’ hypothesis proposes that blastocyst polarity arises from asymmetries that are generated during early cleavage of the embryo. Thus, it predicts that either composition or behaviour of blastomeres differ along the future axes of the embryo, resulting in the overall polarised form of the blastocyst.
