Control of the proportion of inner cells by asymmetric divisions and the ensuing resilience of cloned rabbit embryos

Development. 2018 Apr 18;145(8):dev152041. doi: 10.1242/dev.152041.


Mammalian embryo cloning by nuclear transfer has a low success rate. This is hypothesized to correlate with a high variability of early developmental steps that segregate outer cells, which are fated to extra-embryonic tissues, from inner cells, which give rise to the embryo proper. Exploring the cell lineage of wild-type embryos 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 effects on the proportion of inner cell. In wild type and clones, similar patterns of outer cell asymmetric divisions are shown to be essential to the robust proportion of inner cells observed in wild type. Asymmetric inner cell division, which is not described in mice, is identified as a regulator of the proportion of inner cells and likely gives rise to resilient clones.

Keywords: 3D+time 2-photon imaging; Asymmetrical divisions; Cell death; Digital specimens; In silico experimentation; Rabbit pre-implantation development; Somatic cell nuclear transfer; Spatial cell segregation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asymmetric Cell Division*
  • Blastocyst Inner Cell Mass / cytology*
  • Cell Count
  • Cell Death
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Cloning, Organism / methods*
  • Computer Simulation
  • Embryonic Development
  • Female
  • Green Fluorescent Proteins / genetics
  • Imaging, Three-Dimensional
  • Male
  • Microscopy, Fluorescence, Multiphoton
  • Nuclear Transfer Techniques
  • Pregnancy
  • Rabbits


  • enhanced green fluorescent protein
  • Green Fluorescent Proteins