Mechanism of first cleavage specification in the mouse egg: is our body plan set at day 0?

In most animals the body axis is specified in the egg. Because of their highly regulative capacity after experimental manipulations, mammalian preimplantation embryos have long been thought to be an exception to this rule, lacking polarity until the blastocyst stage. However, it has recently been suggested that the embryonic-abembryonic (Em-Ab) axis of the mouse blastocyst arises perpendicular to the first cleavage plane. Considering the second polar body (2pb) as a stationary marker for the "animal pole (A-pole)" during preimplantation development, the authors concluded that the polarity of the mouse embryo is already specified in the egg, as is the case for most non-mammalian animals. However, the results of our recent time-lapse recordings have shown(8) that in 50% of the embryos the first cleavage occurs at a considerable distance from the "animal-vegetal (A-V) axis" and that the 2pb moves towards the first cleavage plane, in contrast to the previous claims. Thus, there is no predetermined axis in the mouse egg. We also presented a novel model for specification of the first cleavage plane: this is defined as the plane separating the two apposing pronuclei that have moved to the center of the egg. In this review we will elucidate the discrepancy between the previous model and our model, and discuss the possible causes.