Variation and selection in the cell lineage of normal and cloned rabbit embryos

Variation and natural selection underlie evolution. Although variability and robustness are essential characteristic of biological processes, they remain ill defined and poorly understood. Thanks to recent advances in microscopy and computer science, variation in cell behaviors along the cell lineage can be observed and quantified. We reconstructed the entire cell lineage of developing rabbit embryos and compared three wild-type embryos and two nuclear transferred clones, imaged live throughout preimplantation stages, e.g. 32-cell stage to hatching. In wild-type embryos, our quantitative analysis suggests that the number of inner cells is regulated by the occurrence of asymmetric divisions. In addition, asymmetric divisions of inner cells may specifically regulate the size of the inner cell mass. Furthermore, in our cloned embryos, the number of inner cells is highly variable compared to that of outer cells. And this seems to be directly correlated to their cell death rate. As far as we can tell, outer cells in wild-type embryos and clones behave the exact same way. And the cell death rate of outer and inner cells is the same in wild-type embryos. We propose that the variability of inner cells? death in cloned embryos may depend on the epigenetic state of donor cells. Our current working hypothesis is that the success of cloning would depend on the epigenetic state of donor cells and we propose to correlate their potential with their transcriptomic variability.