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Just the right size

The separation of the genetic material in form of chromosomes depends on a microtubule structure called the spindle. Spindle formation and function are complex and involve several regulators, which all have to precisely collaborate to faithfully distribute chromosomes during the cell division process. A recent publication by the HFSP Research Grant Awardee Arp Schnittger and team presents the first spindle as a 3D computational model, allowing to test and further explore the molecular processes of chromosome segregation by the spindle.

During cell division, the previously duplicated chromosomes, the carriers of the genetic information, must be distributed to the daughter cells in such a way that each daughter cell receives exactly one complete set of chromosomes. The chromosomes are distributed by the spindle, which usually forms in the middle of the dividing cell. Each spindle has two poles, one in each future daughter cell, to which one of the duplicated chromosomes is then moved. Disruptions in this process can lead to severe developmental disorders such as Down's syndrome or cancer.

© François Nédélec and Helen Saville, University of Cambridge, United Kingdom

 

Dozens of proteins are involved in the formation of the spindle. The function of which is often not or only partially understood. A computer simulation could therefore be used to test whether the data already collected is sufficient to create a complex structure such as the spindle. In addition, other characteristics that are not yet known can be predicted and used as a hypothesis for experimental work.

Many studies on cell division have used the frog Xenopus laevis or the baker's yeast Saccharomyces cerevisiae as model systems. However, the spindle in the frog is very large (40um) and contains approx. 300,000 microtubules. This size makes a computer simulation extremely difficult. In contrast, the spindle in yeast is relatively small (1.4 um) and is formed by only about 40 microtubules. The spindle of Arabidopsis thaliana, a widely used model in molecular plant research, lies between these extremes with a length of approx. 8 um and 2,000 microtubules.

Now, the international HFSP Research Grant team, including researchers from the UK, France, and Belgium and led by Arp Schnittger, a scientist at the University of Hamburg, Germany, has created the first three-dimensional computer simulation of the Arabidopsis spindle and, thus, of a spindle at all. The team was also able to experimentally identify an important regulator of spindle formation and validate their simulation using plants in which the described spindle regulator was not functional anymore. This simulation will be an important tool for researchers studying microtubule dynamics and cell division control.

Reference

The cell cycle controls spindle architecture in Arabidopsis by activating the augmin pathway.
Romeiro Motta M, Nédélec F, Saville H, Woelken E, Jacquerie C, Pastuglia M, Stolze SC, Van De Slijke E, Böttger L, Belcram K, Nakagami H, De Jaeger G, Bouchez D, Schnittger A. Dev Cell. 2024 Aug 23:S1534-5807(24)00484-2. doi: 10.1016/j.devcel.2024.08.001. 

 

HFSP reference: RGP0023/2018

HFSP Research Grant Awardees: 

  • Arp Schnitter, University of Hamburg, GERMANY
  • Jacques Dumais, Universidad Adolfo Ibáñez, CHILE
  • Olivier Hamant, Laboratoire Reproduction et Développement des Plantes - INRA, CNRS, UCBL1, ENS de Lyon, FRANCE
  • Eric Mjolsness, University of California, USA