Mammalian embryo cloning by nuclear transfer has a low success rate. This is hypothesized to correlate with a high variability of early developmental steps segregating outer cells, fated to extraembryonic tissues, from inner cells, giving rise to the embryo proper. Exploring the cell lineage of wild-type embryos (WT) and clones, imaged in toto until hatching, highlights the respective contributions of cell proliferation, death and asymmetric divisions to phenotypic variability. Preferential cell death of inner cells in clones, probably pertaining to the epigenetic plasticity of the transferred nucleus, is identified as a major difference with consequences on the inner cell proportion. In WT and clones, similar patterns of outer cell asymmetric divisions are shown to be essential to the robust inner cell proportion observed in WT. Asymmetric inner cell division, not described in mice, is identified as a regulator of the inner cell proportion, likely to give rise to resilient clones.
Control of inner cells' proportion by asymmetric divisions and ensuing resilience of cloned rabbit embryos
Present address: Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
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