The inside-outside model of cell-fate specification in pre-implantation mammalian embryos proposes that blastomeres on the inside of the 16-cell stage embryo adopt an inner cell mass (ICM) fate, whereas those on the outside adopt a trophectoderm (TE) fate. Cell-cell contact should therefore be a key factor in this cell-fate specification event. On p. , Chanchao Lorthongpanich and colleagues test this prediction by analysing the gene expression patterns of individual blastomeres separated from two-cell stage mouse embryos and re-separated after every subsequent cell division. Each singled blastomere has a unique gene expression pattern that is not characteristic of either ICM or TE, but that leans towards that of TE. Notably, embryos reconstructed from singled blastomeres are incapable of gastrulation but singled blastomeres preferentially contribute to the TE lineage when aggregated with intact embryos. Thus, the authors propose that a developmental clock drives the random expression of lineage-specific genes in pre-implantation embryos, but correct patterning of lineage-specific gene expression and proper embryonic development requires positional signals and cell-cell interactions.
