When meiosis and crossovers go awry, the organism is faced with severe consequences like less healthy oocytes, lower sperm count or, in the worst case, infertility or miscarriages. A crucial step for successful crossovers is that the chromosomes align pairwise next to each other without being entangled. This is mediated by rapid chromosome movements, where chromosome ends are dragged along the inside membrane of the cell nucleus. This could be compared to two people standing in a room across from each other but being tied with one hand to the wall. How will they be able to stand next to one another?
By using the nematode Caenorhabditis elegans, the group of Verena Jantsch has been studying chromosome movement for a long time. “Lamins are known to support the shape and stability of the nucleus. The intricate network that lamins build is quite stiff and rigid. We wanted to know whether this rigidity of the lamina would pose an obstacle to the choreography of the chromosome dance. Movement is driven by microtubules in the cytoplasm, and the forces are transmitted through a protein interaction module spanning the nuclear membranes, to which one or both ends of the chromosomes are coupled. The lamina network is underneath the nuclear membranes,” explains first author Jana Link.
The researchers were able to show how lamins behave during this crucial chromosome movement process. They discovered that the lamina network within the cell nucleus loosens up during meiosis, allowing the rapid movement of the chromosomes. Shared first author Dimitra Paouneskou explains: “By using the above analogy, we can say that the loosening of the lamin network is like slightly opening up the knots that tie the one hand of the person to the wall. This way, both persons can now move easily towards one another, while walking alongside the wall”. Remarkably, the transient and reversible opening of the lamin network is timed exactly to the chromosome movement, which ensures that chromosomes can be aligned without being entangled or end up in a mess.
Most interestingly, cross talk between the lamina opening and events at the chromosomes themselves does exist. When the scientists artificially increased the rigidity of the lamina, they observed that the chromosomal movement was severely slowed down. This resulted in abnormal chromosome forms in nuclei, which were effectively culled by apoptosis. These described mechanisms of chromosomal movement are very conserved and thus comparable to the ones observed in mammals. Therefore, the results of this study provide an incentive to examine whether similar mechanisms are operating in mammalian cells, since chromosome mis-segregation can have fatal consequences on the health of the offspring in mammals as well.
Publication in Developmental Cell
Jana Link, Dimitra Paouneskou, Maria Velkova, Anahita Daryabeigi, Triin Laos, Sara Labella, Consuelo Barroso, Sarai Pacheco Pinol, Alex Montoya, Holger Kramer, Alexander Woglar, Antoine Baudrimont, Sebastian Mathias Markert, Christian Stigloher, Enrique Martinez-Perez, Alexander Dammermann, Manfred Alsheimer, Monique Zetka, and Verena Jantsch: Transient and Partial Nuclear Lamina Disruption Promotes Chromosome Movement in Early Meiotic Prophase. Developmental Cell, 2018