Cell Division and Reproduction
Group Leader: Julien DUMONTPhD, Research Director CNRS
Institut Jacques Monod
Bât. Buffon – Room 402-404B
15 rue Hélène Brion
75205 Paris Cedex 13 – FRANCE
Approximately 15% of couples are confronted with an infertility problem. The potential causes are the poor quality of the germ cells or gametes (sperm and oocyte), or an impaired embryo development. A major challenge in reproductive biology is to understand the mechanisms of these defects.
During cell division, the chromosomes, carriers of genetic information, are divided into two equal sets between the daughter cells. The faithful distribution of chromosomes is a fundamental element of the genetic stability of cells and organisms. Aneuploidy, which corresponds to the presence of an incorrect number of chromosomes, leads to the formation of embryos that are generally non-viable or show severe developmental defects. Our project aims to study the mechanisms that ensure the formation of oocytes and embryos with the correct number of chromosomes, which is essential for reproduction.
We study the mechanisms of assembly and the functioning of the cellular machinery allowing the correct distribution of chromosomes in meiosis and mitosis. This machinery is composed of a spindle formed by microtubules (green in figure 1), some of which contact chromosomes (magenta). Interactions between spindle microtubules and chromosomes are central to the process of chromosome segregation and are regulated differently in meiosis and in mitosis.
Our approach is multidisciplinary and relies on state-of-the-art genetic, biochemical, cellular and microscopic tools. Our favorite model system is the nematode worm Caenorhabditis elegans, which shares the vast majority of its genes and key mechanisms of reproduction and development with mammals. We also study “non-model” nematodes to develop an evolutionary understanding of the mechanisms of cell division in the context of reproduction.
Quantitative biology and modeling , Development and evolution , Cellular dynamics and signaling , Genome and chromosome dynamics , Models, Molecular and cellular pathologies
1/ Edwards, F., Maton, G., Gareil, N., Canman, J.C. & Dumont, J. BUB-1 promotes amphitelic chromosome biorientation via multiple activities at the kinetochore.
eLife 2018;7:e40690 (2018), doi: 10.7554/eLife.40690
2/ Laband, K., Lacroix, B., Edwards, F., Canman, J.C. & Dumont, J.
Live imaging of C. elegans oocytes and early embryos.
Methods Cell Biol, 145:217-236 (2018), doi: 10.1016/bs.mcb.2018.03.025
3/ Lacroix, B., Letort, G., Pitayu, L., Sallé, J., Stefanutti, M., Maton, G., Ladouceur, AM., Canman, J.C., Maddox, PS., Maddox, AS., Minc, N., Nédélec, F. & Dumont, J. Microtubule dynamics scale with cell size to set spindle length and assembly timing.
Dev Cell, 45:496-511 e496. (2018), doi: 10.1016/j.devcel.2018.04.022
Highlighted in Dev Cell 45:421-423, (2018)
Highlighted on F1000 #eval793546852
4/ Laband, K., Le Borgne, R., Edwards, F., Stefanutti, M., Canman, J.C., Verbavatz, J-M. & Dumont, J.
Chromosome segregation occurs by microtubule pushing in oocytes
Nat Comm, Nov 14;8(1):1499, (2017), doi: 10.1038/s41467-017-01539-8
5/ Gigant, E.*, Stefanutti, M.*, Laband, K., Gluszek-Kustusz, A., Edwards, F., Maton, G., Lacroix, B., Canman, J.C., Welburn, J. & Dumont, J.
Inhibition of ectopic microtubule assembly by the kinesin-13 KLP-7MCAK prevents chromosome segregation and cytokinesis defects in oocytes
Development, 144(9):1674-1686, (2017), doi: 10.1242/dev.147504
6/ Maton, G.*, Edwards, F.*, Lacroix, B., Stefanutti, M., Laband, K., Lieury, T., Kim, T., Espeut, J., Canman, J.C., & Dumont, J.
Kinetochore components are required for central spindle assembly
Nat Cell Biol, 17(5):697-705 (2015), doi: 10.1038/ncb3150
7/ Dumont, J., Oegema, K. & Desai, A. A kinetochore-independent mechanism drives anaphase chromosome separation during acentrosomal meiosis.
Nat Cell Biol, 12(9):894-901 (2010), doi: 10.1038/ncb2093
Dispatched in Current Biology 25, R554–R557, (2015).