Zygote manipulation revealed an overriding effect of cell shape on cleavage orientation. When zygotes were slightly flattened, the cleavage plane went through the short axis of the cell, no matter where the pronuclei were positioned. Pronuclei usually align along the long axis in flattened zygotes, which may explain why past experiments suggested that the cleavage plane lay between, not parallel to, the pronuclei.
The ability to change the zygote's choice of cleavage plane allowed the authors to show that the cleavage itself predicts the blastocyst axis. Whether the cleavage was along the original or the shape-imposed axis, one resulting cell became the embryonic part of the blastocyst, while the other cell became the abembryonic part.
A more difficult problem to tackle will be determining how the two blastomeres differ. “Fate may be determined by the split of components,” says Zernicka-Goetz. But this would require that “reorienting the first cleavage resegregates other things in the egg,” she says. Alternatively, each half may be equally competent to acquire either fate, but subsequent divisions impose the separate fates.