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Parental chromosomes are together but still apart at first mitosis

A recent finding by a team of researchers from European Molecular Biology Laboratory on the parental chromosomes during the first mitosis of an embryo implicates a possible revision in biology textbooks. What they observed during the first mitotic division after the supposed “union” of gametes in mouse models apparently invalidates what is currently believed. Biologists assume that there is only one spindle apparatus that works to separate the two parental chromosomes during the first cell division of a mammalian zygote. It turns out that there are two. Their finding could also help explicate the common errors occurring during the first divisions in the early embryos of mammals, and possibly of humans.

 

 

Early model of mitosis in mammalian zygote

Mitosis of a human cell. In this image, the microtubules are shown in green, chromosomes (DNA) in blue, and kinetochores in red.

 

The first mitosis in mammals occurs during the union of male and female chromosomes. Upon fertilization, the zygote holds two parental chromosomes that unite, and then separated, triggering the formation of two cells (each with own nucleus) after the first mitosis. This marks the two-cell stage embryo.

The first mitosis is thought to proceed initially by the break-down of the nuclear envelope. This enabled the two parental chromosomes to unite thereafter. A single spindle assembly then forms. The spindles attach to the chromosomes, align them at metaphase, and then pull them apart during anaphase. The first mitosis ends at telophase where the cell divides into two cells, each with its own nucleus.

 

 

Viewing first mitosis through light-sheet microscopy

Researchers from European Molecular Biology Laboratory found out that there is not one but two spindle apparatus at work during the first mitosis of the mouse embryo. Using a light-sheet microscopy approach, they were able to conduct real-time, 3D imaging of the mouse embryo.1 Without this innovative technology, capturing an image at this stage will not be feasible because embryos are sensitive to light. With it, the researchers were able to track the chromosomes during the supposed union and saw differently what has long been held. They were surprised to find out that (1) the maternal and the paternal chromosomes assembled their own autonomous spindle structure and (2) the parental chromosomes remain in separate regions and did not mix prior to and during the first mitosis.1,2

 

 

Current model of first mitosis

Based on the current mouse embryo model, what transpires at first mitosis after the nuclear envelope disintegration post-fertilization event is that both the maternal and the paternal chromosomes form their own spindle apparatus. The mitotic spindles then attach to the chromosomes. Even so, the maternal and the paternal chromosomes remain in separate regions of the spindle. The spindles align them in a way that the maternal chromosomes align juxtapose to where the paternal chromosomes align. The two spindle apparatus then autonomously pull them apart towards opposite poles. The cell finally divides into two, where each has only one nucleus. Conversely, an erroneous axis alignment of paternal chromosomes during metaphase was observed to lead to the formation of one of the cells with multiple nuclei after the first mitosis.

The recent findings could help explain certain errors (e.g. multiple-nucleated cell) following the first mitosis. If this mechanism holds true to humans as well it could lead to new targets for treatment (particularly an erring first mitotic spindle apparatus) in a developing embryo. It might also provide an insight as to when life can be assumed to first exist — is it during the first meet-up of the male and the female chromosomes that do not mix yet… or is it that point at which they unite — but apparently occurs only after the first mitosis.

 

 

— written by Maria Victoria Gonzaga

 

 

 

References:

1 Reichmann, J., Nijmeijer, B., Hossain, M. J., Eguren, M., Schneider, I., Politi, A.Z., Roberti, M.J., Hufnagel, L., Hiiragi, T. & Ellenberg, J. (2018). Dual-spindle formation in zygotes keeps parental genomes apart in early mammalian embryosScience. DOI: 10.1126/science.aar7462

2 Zielinska, A.P. & Schuh, M. (2018). Double trouble at the beginning of life. Science  361 (6398): 128-129. DOI: 10.1126/science.aau3216