EMBL scientists show that mammalian life begins differently than we thought
It was long thought that during an embryo’s first cell division, one spindle is responsible for segregating the embryo’s chromosomes into two cells. EMBL scientists now show that in mice, there are actually two spindles, one for each set of parental chromosomes, meaning that the genetic information from each parent is kept apart throughout the first division. Science publishes the results – bound to change biology textbooks – on 12 July 2018.
Artistic 3D rendering of the dual spindle in the mammalian zygote. IMAGE: Cartasiova/Hoissan/Reichmann/Ellenberg/EMBL
Green represents the microtubules that make up the spindle, and pink represents the centrosome: the main microtubule organizing center (MTOC). Blue represents DNA, and orange represents kinetochores: protein structures where the microtubules attach during cell division, to pull chromosomes apart.
This dual spindle formation might explain part of the high error rate in the early developmental stages of mammals, spanning the first few cell divisions. “The aim of this project was to find out why so many mistakes happen in those first divisions,” says Jan Ellenberg, the group leader at EMBL who led the project. “We already knew about dual spindle formation in simpler organisms like insects, but we never thought this would be the case in mammals like mice. This finding was a big surprise, showing that you should always be prepared for the unexpected.”
Solving a 20-year-old mystery
Scientists have always seen parental chromosomes occupying two half-moon-shaped parts in the nucleus of two-cell embryos, but it wasn’t clear how this could be explained. “First, we were looking at the motion of parental chromosomes only, and we couldn’t make sense of the cause of the separation,” says Judith Reichmann, scientist in EMBL’s Ellenberg group and first author of the paper. “Only when focusing on the microtubules – the dynamic structures that spindles are made of – could we see the dual spindles for the first time. This allowed us to provide an explanation for this 20-year-old mystery.”
New molecular targets
“The dual spindles provide a previously unknown mechanism – and thus a possible explanation – for one of the common mistakes we see in the first divisions of mammalian embryos,” Ellenberg explains. Such mistakes can result in cells with multiple nuclei, terminating development. “Now, we have a new mechanism to go after and identify new molecular targets. It will be important to find out if it works the same in humans, because that could provide valuable information for research on how to improve human infertility treatment, for example.”
The beginning of life
Furthermore, the knowledge from this paper might impact legislation. In some countries, the law states that human life begins – and is thus protected – when the maternal and paternal nuclei fuse after fertilisation. If it turns out that the dual spindle process works the same in humans, this definition is not fully accurate, as the union in one nucleus happens slightly later, after the first cell division.
Impossible until now
This discovery would have been impossible without the light-sheet microscopy technology developed in Ellenberg’s and Lars Hufnagel’s group at EMBL, which is now available through the EMBL spin-off company Luxendo. This allows for real-time and 3D imaging of the early stages of development, when embryos are very sensitive to light and would be damaged by conventional light microscopy methods. The high speed and spatial precision of light-sheet microscopy drastically reduce the amount of light that the embryo is exposed to, making a detailed analysis of these formerly hidden processes possible.
Research Article: Reichmann, J. et al. Dual spindle formation in zygotes keeps parental genomes apart in early mammalian embryos. Science, published online 12 July 2018.
Original Press Release.