MPI Campus Seminar: Parental genome unification is highly erroneous in mammalian embryos

I investigated the fundamental question of why the vast majority of human embryos are aneuploid they carry an incorrect number of chromosomes. Aneuploidy frequently arises during the early mitotic divisions of the embryo, but the origin of this remains elusive. I established a live cell imaging system to follow the first divisions of bovine embryos, as a model for human embryos. I identify an error-prone mechanism of parental genome unification which often results in aneuploidy. Surprisingly, genome unification initiates hours before breakdown of the two pronuclei that encapsulate the parental genomes. While still within intact pronuclei, the parental genomes polarize towards each other clustering at the pronuclear interface, in direct proximity to each other. Using drug treatments and dominant negatives, I discovered that genome clustering at the pronuclear interface is driven by cytoplasmic microtubules that emanate from centrosomes, typically located between the pronuclei. I found that dynein transduces pulling forces to the chromosomes via nuclear pore complexes, which also cluster at the pronuclear interface. Parental genome clustering often fails however, leading to massive chromosome segregation errors, incompatible with healthy embryo development. Nucleoli, which associate with chromatin, also cluster at the pronuclear interface in human zygotes. Defects in nucleolar clustering correlate with failure in human embryo development, suggesting a conserved mechanism.