Blastomeres arising from the first cleavage division have distinguishable fates in normal mouse development

Two independent studies have recently suggested similar models in which the embryonic and abembryonic parts of the mouse blastocyst become separated a lready by the first cleavage division. However, no lineage tracing studies carried out so far on early embryos provide the support for such a hypothes is. Thus, to re-examine the fate of blastomeres. of the two-cell mouse embr yo, we have undertaken lineage tracing studies using a non-perturbing metho d. We show that two-cell stage blastomeres have a strong tendency to develo p into cells that comprise either the embryonic or the abembryonic parts of the blastocyst. Moreover, the two-cell stage blastomere that is first to d ivide will preferentially contribute its progeny to the embryonic part. Nev ertheless, we find that the blastocyst embryonic-abembryonic axis is not pe rfectly orthogonal to the first cleavage plane, but often shows some angula r displacement from it. Consequently, there is a boundary zone adjacent to the interior margin of the blastocoel. that is populated by cells derived f rom both earlier and later dividing blastomeres. The majority of cells that inhabit this boundary region are, however, derived from the later dividing two-cell stage blastomere that contributes predominantly to the abembryoni c part of the blastocyst. Thus, at the two-cell stage it is already possibl e to predict which cell will contribute a greater proportion of its progeny to the abembryonic part of the blastocyst (region including the blastocyst cavity) and which to the embryonic part (region containing the inner cell mass) that will give rise to the embryo proper.