Specification of embryonic axes begins before cleavage in normal mouse development.

Studies on the development of aggregated, isolated and rearranged blastomeres have engendered the view that in mammals, unlike most other animals, egg organization has no role in the genesis of asymmetries that are essential for cellular diversification and the specification of embryonic axes. Such asymmetries are assumed to arise post-zygotically through interactions between initially naive cells. However, various findings are difficult to reconcile with this view. Here, a consistent relationship between the structure of the blastocyst and the two-cell stage in the mouse has been found using a strictly non-invasive marking technique: injection of small oil drops into the substance of the zona pellicuda. This has revealed that both the embryonic-abembryonic axis of the blastocyst and its plane of bilateral symmetry are normally orthogonal to the plane of first cleavage. This relationship was also seen when denuded two-cell conceptuses were prevented from rotating during subsequent cleavage by immobilizing them in a gel. Therefore, during normal mouse development the axes of the blastocyst, which have been implicated in establishing those of the fetus, are already specified by the onset of cleavage.