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Proclaiming fate in the early mouse embryo

Nature Cell Biology volume 13, pages 112–114 (2011)Cite this article

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In the mouse embryo, the first differences between cells that result in distinct lineages have long been thought to arise only as a consequence of differential cell positioning at relatively late preimplantation stages. Differences in Oct4 transcription factor kinetics between cells at the 4–8-cell stage are now shown to be predictive of future lineages, providing further evidence for much earlier initiation of cell fate decisions.

The authors use time-lapse confocal microscopy imaging to quantify the fluorescent decay after photo-activation (FDAP) of photo-activatable GFP–Oct4, and thus follow the kinetics of nuclear export, import and retention of Oct4 in 4- and 8-cell stage cell nuclei. The non-invasive nature of this technique is an important aspect of this study, as it sidesteps the difficulties imposed by the ability of mouse embryo cells to regulate their development and adopt new fates in response to experimentation. Plachta et al.13 discovered that although morphologically indistinguishable, the 4- and 8-cell stage cells fell into two distinct categories with respect to their Oct4 kinetics that seemed to reflect differences in the accessibility of Oct4 to its DNA-binding sites. One category was characterized by low rates of nuclear export/import and a highly immobile fraction of Oct4 protein in the nucleus, whereas high rates of export and import and highly mobile Oct4 protein was seen in the second group, which also displayed lower levels of nuclear Oct4. To determine whether these differential Oct4 kinetics reflected a bias in cell fate, the authors followed the lineages of cells displaying different Oct4 kinetics in vivo. This revealed that cells characterized by the highly immobile nuclear fraction of Oct4 preferentially underwent asymmetric cell divisions and so contributed significantly more cells to the ICM. In contrast, the progeny of cells with faster Oct4 export/import dynamics divided preferentially symmetrically and contributed to the trophectoderm. Thus, these differences in Oct4 kinetics between morphologically identical cells at the 4- and 8-cell stages were predictive of the later cell lineages, and therefore challenge the belief that the first cell fate decision point is coincident with the differential positioning of cells.

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Figure 1: Oct4 kinetics at the 4–8 cell stage influence cell fate decisions.

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  1. Magdalena Zernicka-Goetz is in the Gurdon Institute, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, UK. m.zernicka-goetz@gurdon.cam.ac.uk,

    Magdalena Zernicka-Goetz

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Zernicka-Goetz, M. Proclaiming fate in the early mouse embryo. Nat Cell Biol 13, 112–114 (2011). https://doi.org/10.1038/ncb0211-112

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