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Mechanisms of Meiosis – MOM

Katja WASSMANN

Sexual reproduction requires the generation of haploid gametes through two meiotic divisions, named meiosis I and II. In mammals and especially humans, female gametogenesis is highly error prone, leading to the generation of oocytes harbouring the wrong chromosome content.

Projects in my group aim at dissecting the molecular mechanisms underlying the two meiotic divisions with a focus on oocytes, to understand how errors occur. The central question we study deals with the issue of how meiosis I-specific events are executed only in meiosis I, and those of meiosis II only in meiosis II.

Keywords: Meiosis, Oocytes, Cohesin, Phosphoproteome, Cell cycle, Aneuploidy

+33 (0)157278148    katja.wassmann(at)ijm.fr    https://www.researchgate.net/profile/Katja-Wassmann

Research

  • In meiosis, key events need to happen in the correct order, and at the right time, otherwise the generation of healthy gametes is compromised. In our projects we focus on elucidating the underlying regulatory mechanisms of meiosis-specific events with a special focus on oocytes, to gain insights into how these events are put into place in the correct developmental context, e.g. meiosis I or II.Specific features of the meiotic divisions (meiosis I and II):
    • Homologous chromosomes (each consisting of two sister chromatids) are paired and segregated in meiosis I, and sister chromatids in meiosis II
    • Kinetochores (the attachment sites for the bipolar spindle) of the two paired sister chromatids are co-oriented to the same pole in meiosis I, and bioriented to opposite poles in meiosis II (named mono- and bipolar orientation or attachment, respectively).
    • The cohesin complex, which is holding sister chromatids together, is removed in a step-wise manner, from chromosome arms in meiosis I, and the centromere region in meiosis II.
    • Transition from meiosis I into meiosis II occurs without intervening S-phase

     

    An additional specificity of vertebrate oocytes is the requirement to implement two cell cycle arrests: One before entry into meiosis I, in prophase I, which lasts decades in humans; a second arrest in metaphase of meiosis II, called CSF-arrest, to await fertilization.

     

    The overarching question of our projects is the following:

    How are the two successive meiotic divisions implemented without mixing up meiosis I and meiosis II specific events?

 

         Our research questions:

 

  • Model systems we use in the lab:Projects1) Meiotic cell cycle control, Cdk-Cyclin specificities and threshold levelsWe think that a global view on mitotic kinase substrate phosphorylation and dephosphorylation, to dissect common principles governing the meiotic divisions, will be key to understand how transition from meiosis I to meiosis II is regulated. Currently we use budding yeast as a model system for this question, to gain insights into this special cell cycle transition in a simple model system, removing an additional layer of complexity that can be expected in oocytes.Additionally, we study Cyclin specificity and Cdk threshold levels for implementing meiosis-specific cell cycle events, using frog and mouse oocytes. We have discovered that at least two M-phase cyclins- Cyclin A2 and B3- occupy specific roles that are not redundant with other cyclins. Both cyclins have functions related to ordering meiosis I and meiosis II-specific events. Our projects aim at identifying specific substrates of these cyclins, and the molecular mechanisms underlying their meiosis-specific roles. 

    2) Step-wise cohesin removal in mammalian oocytes

     

    Step-wise cohesin removal is brought about by protection of the centromeric cohesin subunit Rec8 from cleavage by the protease Separase at the centromere region in meiosis I, and by removing this protection before sister chromatid segregation in meiosis II. Protection is due to the recruitment of Sgo2, which brings the phosphatase PP2A to the centromere to maintain Rec8 there in a dephosphorylated state. However, several open questions are remaining, starting with the question of how Separase activity is controlled to get inhibited and activated twice, and how proteins involved in protection do so in meiosis I, but not meiosis II, and only in the centromere region.

     

    3) Kinetochore attachments and checkpoint controls in mammalian oocytes

     

    Again related to our main question of how meiosis I and meiosis II events are implemented at the correct time, we want to understand how checkpoints can recognize the correct attachments in their proper context, e.g. monopolar attachments to segregate chromosomes in meiosis I, and bipolar attachments in meiosis II to segregate sister chromatids. Additionally we address whether both kinetochores are functional in meiosis I when they are mono-oriented and fused.

 

 

Members

Group Leader:

Katja WASSMANN
Phone : +33 (0)157278148
Mail : katja.wassmann (at) ijm.fr

Members:

Eulalie BUFFIN, MCF

Aude DUPRE, CR

Sandra TOUATI, CR

Safia EL JAILANI, PhD Student

Damien CLADIERE, Engineer

Samih EL AARAJ, Master 2

Emmanuelle MARJAULT, Engineer

Irem POLAT, PhD Student

 

 

Selected Publications

Bouftas N.*, Schneider L.*, Halder M., Demmig R., Baack M., Cladière D., Walter M., Al Abdallah H., Kleinhempel C., Messaritaki R., Müller J., Passarelli F., Wehrle P., Heim A., Wassmann K.#+ and Mayer T.U.#

Cyclin-B3 prevents Emi2/Xerp1 from setting up precocious CSF-arrest in oocyte meiosis I,

Dev. Cell (2022) 57, 2305-2320

(*co first-authors, #co-corresponding authors, +lead author)

 

Nikalayevich E., El Jailani S., Cladière D., Gryaznova Y., Fosse C., Touati S.A., Buffin E., and Wassmann K.

Aurora B/C-dependent phosphorylation promotes Rec8 cleavage in mammalian oocytes

Current Biology (2022) doi: 10.1016/j.cub.2022.03.041, in press

 

Gryaznova Y., Keating L.*, Touati S.A.*, Caldière D., El Yakoubi W., Buffin E., and Wassmann K.

Kinetochore individualization in meiosis I is required for centromeric cohesin removal in meiosis II,

EMBO J. (2021) 40, e106797                         (*co second-authors)

 

Mehmet E. Karasu*, Bouftas N.*, Keeney S., and Wassmann K.

Cyclin B3 promotes anaphase I onset in oocyte meiosis,

J Cell Biol. (2019) 218, 1265-1281                            (*co first-authors)

 

Vallot A., Leontiou I., El Yakoubi W., Cladière D., Bolte S., Buffin E.*, and Wassmann K.*+

Tension-induced error correction, and not kinetochore attachment status activates the SAC in an Aurora-B/C-dependent manner in oocytes,

Current Biology (2018) 28, 130-139                            (*co-corresponding authors, + lead author )

 

El Yakoubi W., Buffin E., Cladière D, Gryaznova Y., Berenguer I., Touati S.A., Gómez R. , Suja J.A.,van Deursen J.M., and Wassmann, K.

Mps1 kinase-dependent Sgo2 centromere localization mediates cohesin protection in mouse oocyte meiosis I,

Nature Communications (2017) DOI: 10.1038/s41467-017-00774-3

 

Touati S., Buffin E., Cladière D., Rachez C., Hached K., van Deursen J.M., and Wassmann K.

Mouse oocytes depend on BubR1 for proper chromosome segregation but not prophase I arrest,

Nature Communications (2015) DOI: 10.1038/ncomms7946

 

Chambon J.P., Touati S., Berneau S., Cladière D., Hebras C., Groeme R., McDougall A., and Wassmann K.

The PP2A inhibitor I2PP2A is essential for sister chromatid segregation in meiosis II,

Current Biology (2013) 23, 485-490

 

Touati S., Cladière D, Lister L.M., Leontiou I., Chambon J.P., Rattani A., Böttger F., Stemmann O., Nasmyth K., Herbert M., and Wassmann K.

Cyclin A2 is required for sister chromatid segregation, but not Separase control, in mouse oocyte meiosis,

Cell Reports (2012) 29, 1077-1087

 

Kudo N.R.*, Wassmann K.*, Anger M., Schuh M., Wirth G.K., Xu H., Helmhart W., Kudo H., Mckay M., Maro B., Ellenberg J., de Boer P., and Nasmyth K.

Resolution of Chiasmata in Oocytes Requires Separase-Mediated Proteolysis,

Cell (2006) 126, 135-146                               (*co first-authors)

 

Wassmann K.*, Niault T., and Maro B.

Metaphase I Arrest Upon Activation of the Mad2-Dependent Spindle Checkpoint in Mouse Oocytes

Curr. Biol. (2003) 13, 1596-1608                   (*corresponding author)

All the publications

Publications

Varela Salgado, M., Adriaans, I. E., Touati, S. A., Ibanes, S., Lai-Kee-Him, J., Ancelin, A., Cipelletti, L., Picas, L., & Piatti, S. (2024). Phosphorylation of the F-BAR protein Hof1 drives septin ring splitting in budding yeast. Nature Communications, 15(1), 3383. https://doi.org/10.1038/s41467-024-47709-3
Celebic, D., Polat, I., Legros, V., Chevreux, G., Wassmann, K., & Touati, S. A. (2024). Qualitative rather than quantitative phosphoregulation shapes the end of meiosis I in budding yeast. The EMBO Journal. https://doi.org/10.1038/s44318-024-00032-5
Dupré, A., & Wassmann, K. (2023). [Cyclin B3: Locking female meiosis to await fertilization]. Medecine Sciences: M/S, 39(3), 289–292. https://doi.org/10.1051/medsci/2023019
Nikalayevich, E., & Wassmann, K. (2022). Protocol to measure cleavage efficiency of the meiotic cohesin subunit Rec8 by separase in mouse oocytes using a biosensor. STAR Protocols, 3(4), 101714. https://doi.org/10.1016/j.xpro.2022.101714
Wassmann, K. (2022). Separase Control and Cohesin Cleavage in Oocytes: Should I Stay or Should I Go? Cells, 11(21), 3399. https://doi.org/10.3390/cells11213399
Bouftas, N., Schneider, L., Halder, M., Demmig, R., Baack, M., Cladière, D., Walter, M., Al Abdallah, H., Kleinhempel, C., Messaritaki, R., Müller, J., Passarelli, F., Wehrle, P., Heim, A., Wassmann, K., & Mayer, T. U. (2022). Cyclin B3 implements timely vertebrate oocyte arrest for fertilization. Developmental Cell, 57(19), 2305-2320.e6. https://doi.org/10.1016/j.devcel.2022.09.005
Nikalayevich, E., El Jailani, S., Dupré, A., Cladière, D., Gryaznova, Y., Fosse, C., Buffin, E., Touati, S. A., & Wassmann, K. (2022). Aurora B/C-dependent phosphorylation promotes Rec8 cleavage in mammalian oocytes. Current Biology, 32(10), 2281-2290.e4. https://doi.org/10.1016/j.cub.2022.03.041
Gryaznova, Y., Keating, L., Touati, S. A., Cladière, D., El Yakoubi, W., Buffin, E., & Wassmann, K. (2021). Kinetochore individualization in meiosis I is required for centromeric cohesin removal in meiosis II. The EMBO Journal, 40(7), e106797. https://doi.org/10.15252/embj.2020106797
Lemonnier, T., Daldello, E. M., Poulhe, R., Le, T., Miot, M., Lignières, L., Jessus, C., & Dupré, A. (2021). The M-phase regulatory phosphatase PP2A-B55δ opposes protein kinase A on Arpp19 to initiate meiotic division. Nature Communications, 12(1), 1837. https://doi.org/10.1038/s41467-021-22124-0
Jones, A. W., Flynn, H. R., Uhlmann, F., Snijders, A. P., & Touati, S. A. (2020). Assessing Budding Yeast Phosphoproteome Dynamics in a Time-Resolved Manner using TMT10plex Mass Tag Labeling. STAR Protocols, 1(1), 100022. https://doi.org/10.1016/j.xpro.2020.100022
Touati, S. A., Hofbauer, L., Jones, A. W., Snijders, A. P., Kelly, G., & Uhlmann, F. (2019). Cdc14 and PP2A Phosphatases Cooperate to Shape Phosphoproteome Dynamics during Mitotic Exit. Cell Reports, 29(7), 2105-2119.e4. https://doi.org/10.1016/j.celrep.2019.10.041
Touati, S. A., Kataria, M., Jones, A. W., Snijders, A. P., & Uhlmann, F. (2018). Phosphoproteome dynamics during mitotic exit in budding yeast. The EMBO Journal, 37(10), e98745. https://doi.org/10.15252/embj.201798745
Vallot, A., Leontiou, I., Cladière, D., El Yakoubi, W., Bolte, S., Buffin, E., & Wassmann, K. (2018). Tension-Induced Error Correction and Not Kinetochore Attachment Status Activates the SAC in an Aurora-B/C-Dependent Manner in Oocytes. Current Biology, 28(1), 130-139.e3. https://doi.org/10.1016/j.cub.2017.11.049
El Yakoubi, W., Buffin, E., Cladière, D., Gryaznova, Y., Berenguer, I., Touati, S. A., Gómez, R., Suja, J. A., van Deursen, J. M., & Wassmann, K. (2017). Mps1 kinase-dependent Sgo2 centromere localisation mediates cohesin protection in mouse oocyte meiosis I. Nature Communications, 8(1), 694. https://doi.org/10.1038/s41467-017-00774-3
Lam, F., Cladière, D., Guillaume, C., Wassmann, K., & Bolte, S. (2017). Super-resolution for everybody: An image processing workflow to obtain high-resolution images with a standard confocal microscope. Methods, 115, 17–27. https://doi.org/10.1016/j.ymeth.2016.11.003
Godfrey, M., Touati, S. A., Kataria, M., Jones, A., Snijders, A. P., & Uhlmann, F. (2017). PP2ACdc55 Phosphatase Imposes Ordered Cell-Cycle Phosphorylation by Opposing Threonine Phosphorylation. Molecular Cell, 65(3), 393-402.e3. https://doi.org/10.1016/j.molcel.2016.12.018
Touati, S. A., Buffin, E., Cladière, D., Hached, K., Rachez, C., van Deursen, J. M., & Wassmann, K. (2015). Mouse oocytes depend on BubR1 for proper chromosome segregation but not for prophase I arrest. Nature Communications, 6(1), 6946. https://doi.org/10.1038/ncomms7946
Cyclin B3 promotes anaphase I onset in oocyte meiosis | Journal of Cell Biology | Rockefeller University Press. (n.d.). Retrieved April 5, 2024, from https://rupress.org/jcb/article/218/4/1265/61870/Cyclin-B3-promotes-anaphase-I-onset-in-oocyte

 

Reviews

Dupré, A., & Wassmann, K. (2023). La cycline B3, verrou de la méiose femelle en attendant la fécondation. médecine/sciences, 39(3), 289–292. https://doi.org/10.1051/medsci/2023019
Bouftas, N., & Wassmann, K. (2022). Working in close quarters: biparental meiosis in the oocyte. EMBO Reports, 23(7), e55360. https://doi.org/10.15252/embr.202255360
Lemonnier, T., Dupré, A., & Jessus, C. (2020). The G2-to-M transition from a phosphatase perspective: a new vision of the meiotic division. Cell Division, 15(1), 9. https://doi.org/10.1186/s13008-020-00065-2
Keating, L., Touati, S. A., & Wassmann, K. (2020). A PP2A-B56—Centered View on Metaphase-to-Anaphase Transition in Mouse Oocyte Meiosis I. Cells, 9(2), 390. https://doi.org/10.3390/cells9020390
Bouftas, N., & Wassmann, K. (2019). Cycling through mammalian meiosis: B-type cyclins in oocytes. Cell Cycle, 18(14), 1537–1548. https://doi.org/10.1080/15384101.2019.1632139
Touati, S. A., & Uhlmann, F. (2018). A global view of substrate phosphorylation and dephosphorylation during budding yeast mitotic exit. Microbial Cell, 5(8), 389–392. https://doi.org/10.15698/mic2018.08.644
Marston, A. L., & Wassmann, K. (2017). Multiple Duties for Spindle Assembly Checkpoint Kinases in Meiosis. Frontiers in Cell and Developmental Biology, 5. https://doi.org/10.3389/fcell.2017.00109
El Yakoubi, W., & Wassmann, K. (2017). Meiotic Divisions: No Place for Gender Equality. In M. Gotta & P. Meraldi (Eds.), Cell Division Machinery and Disease (pp. 1–17). Springer International Publishing. https://doi.org/10.1007/978-3-319-57127-0_1
Touati, S. A., & Wassmann, K. (2016). How oocytes try to get it right: spindle checkpoint control in meiosis. Chromosoma, 125(2), 321–335. https://doi.org/10.1007/s00412-015-0536-7
Cells | Free Full-Text | Translational Control of Xenopus Oocyte Meiosis: Toward the Genomic Era. (n.d.). Retrieved April 5, 2024, from https://www.mdpi.com/2073-4409/9/6/1502

 

Book chapters

El Jailani, S., Wassmann, K., & Touati, S. A. (2024). Whole-Mount Immunofluorescence Staining to Visualize Cell Cycle Progression in Mouse Oocyte Meiosis. In A. Castro & B. Lacroix (Eds.), Cell Cycle Control: Methods and Protocols (pp. 211–227). Springer US. https://doi.org/10.1007/978-1-0716-3557-5_13
Nikalayevich, E., Bouftas, N., & Wassmann, K. (2018). Detection of Separase Activity Using a Cleavage Sensor in Live Mouse Oocytes. In M.-H. Verlhac & M.-E. Terret (Eds.), Mouse Oocyte Development: Methods and Protocols (pp. 99–112). Springer. https://doi.org/10.1007/978-1-4939-8603-3_11

Theses

Thesis defended:

  • Khaled Hached: 2006-2010
  • Sandra Touati: 2011- 2014
  • Antoine Vallot: 2014-2017
  • Nora Bouftas: 2015-2019
  •  Leonor Keating: 2017-2021

 

Thesis in progress:

  • Antoine Langeoire-Cassalta: 2019-
  • Dunja Čelebić: 2020-
  • Safia El Jailani: 2021-

Collaborations

Thomas Mayer, University of Konstanz, Germany

Evelyn Houliston, Laboratoire Océanologique de Villefranche-sur-Mer, France

GRANTS – FUNDING

Equipe FRM 2021-2024

ANR JCJC 2022-2025

ANR PRC 2019

News

04/07/2023 – Katja Wassmann, election as a member of the EMBO community

Job

We are recruiting an engineer (information to follow)