Published in Current Biology: Simultaneous regulation of cytokinetic furrow and nucleus positions by cortical tension contributes to proper DNA segregation during late mitosis

Simultaneous regulation of cytokinetic furrow and nucleus positions by cortical tension contributes to proper DNA segregation during late mitosis.
Pacquelet, A., Jousseaume M., Etienne J., Michaux G., Current Biology, 31 October 2019

Errors in the distribution of genetic material during cell division can have dramatic consequences on the life of the daughter cells. In a study published in the journal Current Biology, researchers reveal the existence of a mechanism for the correction of errors in the distribution of novel DNA in which changes in cell tension play a vital role.

When a cell divides, its genetic material must be distributed equitably between its two daughter cells. This segregation of genetic material is an essential feature of cell division. In fact, a bad distribution of the DNA causes aneuploidy of the two daughter cells which can lead to their tumoral transformation.

The good distribution of chromosomes during cell division is a complex process, based on the success of several successive steps. The mitotic spindle, a structure composed of microtubules that form at the beginning of cell division, separates chromosomes into two equal lots. This spindle and a cytoskeletal protein, myosin, are then able to control the formation of a circular ring, called the dividing groove, cleaving the mother cell between the two chromosome batches. Despite the existence of this sophisticated cellular machinery, errors can occur in the separation of chromosomes or in the formation of the division furrow. These errors, by preventing the proper distribution of genetic material, can have dramatic consequences for the daughter cells. But mechanisms capable of correcting some of these errors exist. Several processes, involving biochemical signaling pathways, make it possible to correct the errors that occur during the separation of chromosomes by the mitotic spindle. In this study, researchers have demonstrated the existence of a new type of mechanism, based on changes in the biophysical properties of cells and to correct DNA segregation defects caused by errors in the positioning of the cell. division furrow.
For this, they used the caenorhabditis elegans worm embryo at the one-cell stage, the large size of which makes it easy to visualize the stages of division. They observed several types of mutant embryos in which the division furrow is poorly positioned relative to the mitotic spindle. In these embryos, the errors of positioning of the groove are due to an excess of myosin at one pole of the cell and lead initially to major chromosome segregation defects: one daughter-cell inherits all the chromosomes while the other n do not have one. The researchers, however, were surprised to observe that these defects are corrected at the end of cell division. This correction is possible thanks to the displacement of the division groove and to that, in the opposite direction, of one of the nuclei containing the chromosomes. They then combined genetic experiments, voltage and flux measurements and the development of a biophysical model to identify the mechanisms that allow these movements. They showed that the excess of myosin at a pole of the cell causes an excess of tension which induces the formation of "bubbles" in the cellular cortex. These bubbles first allow an expansion of the cortex which participates in the displacement of the division furrow. Then, when the groove is closed, the relaxation due to the formation of cortical bubbles creates a difference in intracellular pressure and results in the creation of a strong cytoplasmic flow. This flow provides the force that allows the groove to continue to move and also causes the displacement of the nucleus.

Thus the excess of myosin which causes the errors of positioning of the division furrow and the initial defects of segregation of the chromosomes also modifies the biophysical properties of the cell, in particular its cortical tension. The resulting physical changes - cortical bubble formation and the appearance of cytoplasmic flow - are responsible for the forces that allow the division furrow and genetic material to move. These biophysical mechanisms are therefore essential to ensure the equitable segregation of chromosomes.
 
 
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© Anne Pacquelet

Figure: An excess of myosin (in magenta on the images on the right) to the cortex leads to a bad positioning of the division furrow during the first division of C. elegans embryos. The two nuclei (containing the chromosomes) are then present in only one of the daughter cells (top images). The formation of cortical bubbles induces the displacement of the division furrow and one of the nuclei, thus allowing a fair distribution of the genetic material (middle and bottom images).

 

Actuality from INSB - CNRS

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