Dual-spindle formation keeps the two parental genomes apart in 1-cell mammalian embryo

Mammalian life begins with fertilization of the egg. Once the egg and sperm have fused, the parental chromosomes need to be combined. It was previously taught that a single microtubule-spindle is responsible for spatially combining the two genomes, and then segregating them, to create the two-cell embryo. Authors [see attached article] discovered that it is not that simple. Unexpectedly, the parental chromosomes do not mix immediately, but rather they occupy distinct zones in the zygote (fertilized egg) throughout the first cellular division. How the autonomy of parental genomes is retained after fertilization –– remains unclear.

Authors used elegant microscopy methods to illuminate this special moment, when the parental chromosomes first meet in live mouse zygotes, and they then followed how the chromosomes become distributed as the zygote divides to become a two-cell embryo. Unexpectedly, the male and female chromosomes each assemble their own chromosome-separation machineries. From an evolutionary survival point-of-view, this would increases the probability that chromosomes are separated into multiple, unequal groups –– which might lead to enhanced diversity in the offspring. Alternatively, this chain-of-events may compromise embryo development and give rise to a spontaneous miscarriage.

Authors labeled the maternal and paternal chromosomes in different colors (by taking advantage of distinct DNA sequences in the parental chromosomes, which came from different mouse strains). Authors then imaged the area of interest at very high spatial and temporal resolution, plus they used an innovative light-sheet microscope –– which illuminates the embryo selectively in the region of interest but not in adjacent regions (as is the case with standard microscopy approaches). This method is fast and allows authors to reconstruct the entire volume occupied by the chromosomes with unprecedented spatial and temporal resolution. In addition, they imaged microtubules, the proteinaceous fibers that form the spindle-apparatus which captures, aligns, and distributes the chromosomes equally between the two daughter-cells of the dividing zygote.

These two spindles aligned their poles before Anaphase (stage of mitosis after Metaphase –– when replicated chromosomes are split and the daughter chromatids are moved to opposite poles of the cell. Chromosomes also reach their overall maximum condensation in late Anaphase, to help chromosome segregation and reformation of the nucleus) –– but kept the parental genomes apart during the first cleavage. This spindle-assembly mechanism provides a potential rationale for erroneous divisions into more than two blastomeric (cells formed by cleavage of the fertilized ovum) nuclei observed in mammalian zygotes. These data reveal the mechanism behind the observation that parental genomes occupy separate nuclear compartments in the two-cell embryo


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