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

  • 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?

    Model systems we use in the lab:

     

    Projects

     

    1) Meiotic cell cycle control, Cdk-Cyclin specificities and threshold levels

     

    We 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.

 

Our research questions:

Group Leader:

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

Members:

Eulalie Buffin, MCF

Aude Dupré, CR

Sandra Touati, CR

Dunja Čelebić, PhD

Safia El Jailani, PhD

Antoine Langoire-Cassalta, PhD

Damien Cladière, Ingénieur

 

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)

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)

 

Nikalayevich E., Bouftas N., and Wassmann K.

A live sensor as a readout for Separase activity in mouse oocyte meiosis,

Methods in Mol. Biol. (2018) 18, 99-112

 

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

 

Lam F., Cladière D., Guillaume C., Wassmann K., and Bolte S.

Superresolution for everybody: An image processing workflow to obtain  3D-SIM-like images in bulky samples with a standard confocal microscope,

Methods, Special Issue: Image Processing in Biology (2016), pii S1046-2023 (16) 30436-4

 

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

 

Reviews

 

Bouftas N. and Wassmann K.

Working in close quarters: Biparental meiosis in the oocyte

Embo Reports, accepted (May 13, 2022)

 

Keating L., Touati S.A., and Wassmann K.

A PP2A-B56 centered view on metaphase-to-anaphase transition in mouse oocyte meiosis I

Cells (2020) 9, 390-406

 

Bouftas N. and Wassmann K.

Cycling through mammalian meiosis: B-type cyclins in oocytes

Cell Cycle (2019)14, 1537-1548

 

Marston A. and Wassmann K.

Multiple duties for spindle assembly checkpoint kinases in meiosis

Front. Cell Dev. Biol. (2017) DOI: 10.3389/fcell.2017.00109

 

El Yakoubi W. and Wassmann K.

Meiotic divisions: no place for gender equality

Adv. Exp. Med. Biol. (2017) 1002, 1-17

 

Touati S.A. and Wassmann K.

How oocytes try to get it right: Spindle checkpoint control in meiosis.

Chromosoma (2016) 125, 321-335

 

Publications des membres de l’équipe depuis 2015

The M-phase regulatory phosphatase PP2A-B55δ opposes protein kinase A on Arpp19 to initiate meiotic division.

Lemonnier T, Daldello EM, Poulhe R, Le T, Miot M, Lignières L, Jessus C, Dupré A.Nat Commun. 2021 Mar 23;12(1):1837. doi: 10.1038/s41467-021-22124-0.PMID: 33758202 Free PMC article.

 

Assessing Budding Yeast Phosphoproteome Dynamics in a Time-Resolved Manner using TMT10plex Mass Tag Labeling.

Jones AW, Flynn HR, Uhlmann F, Snijders AP, Touati SA.STAR Protoc. 2020 Jun 19;1(1):100022. doi: 10.1016/j.xpro.2020.100022.PMID: 32685930 Free PMC article.


Cdc14 and PP2A Phosphatases Cooperate to Shape Phosphoproteome Dynamics during Mitotic Exit.

Touati SA, Hofbauer L, Jones AW, Snijders AP, Kelly G, Uhlmann F.Cell Rep. 2019 Nov 12;29(7):2105-2119.e4. doi: 10.1016/j.celrep.2019.10.041.PMID: 31722221 Free PMC article.

 

Phosphoproteome dynamics during mitotic exit in budding yeast.

Touati SA, Kataria M, Jones AW, Snijders AP, Uhlmann F.EMBO J. 2018 May 15;37(10):e98745. doi: 10.15252/embj.201798745. Epub 2018 Apr 12.PMID: 29650682 Free PMC article.

 

PP2ACdc55 Phosphatase Imposes Ordered Cell-Cycle Phosphorylation by Opposing Threonine Phosphorylation.

Godfrey M, Touati SA, Kataria M, Jones A, Snijders AP, Uhlmann F.Mol Cell. 2017 Feb 2;65(3):393-402.e3. doi: 10.1016/j.molcel.2016.12.018. Epub 2017 Jan 26.PMID: 28132839 Free PMC article.

 

Control of Cdc6 accumulation by Cdk1 and MAPK is essential for completion of oocyte meiotic divisions in Xenopus.

Daldello EM, Le T, Poulhe R, Jessus C, Haccard O, Dupré A.J Cell Sci. 2015 Jul 15;128(14):2482-96. doi: 10.1242/jcs.166553. Epub 2015 Jun 19.PMID: 26092930

 

Reviews:

 

Translational Control of Xenopus Oocyte Meiosis: Toward the Genomic Era.

Meneau F, Dupré A, Jessus C, Daldello EM.Cells. 2020 Jun 19;9(6):1502. doi: 10.3390/cells9061502.PMID: 32575604 Free PMC article. Review.

 

The G2-to-M transition from a phosphatase perspective: a new vision of the meiotic division.

Lemonnier T, Dupré A, Jessus C.Cell Div. 2020 May 25;15:9. doi: 10.1186/s13008-020-00065-2. eCollection 2020.PMID: 32508972 Free PMC article. Review.

 

A global view of substrate phosphorylation and dephosphorylation during budding yeast mitotic exit.

Touati SA, Uhlmann F.Microb Cell. 2018 Jul 25;5(8):389-392. doi: 10.15698/mic2018.08.644.PMID: 30175109 Free PMC article.

 

 

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-

Thomas Mayer, University of Konstanz, Germany

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

Equipe FRM 2021-2024

ANR JCJC 2022-2025

ANR PRC 2019

We are recruiting an engineer (information to follow)