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:

Project 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.

Project 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.

Project 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.

• Team leader

  • 
    Katharina WASSMANN, Chercheur, WASSMANN LAB
    

    +33 (0)1 57 27 81 48, room 322B

  Members

  • 
    Eulalie BUFFIN, Enseignant-chercheur, WASSMANN LAB
    

    +33 (0)1 57 27 80 35, room 322B
  • 
    Damien CLADIERE, Ingénieur en biologie, WASSMANN LAB
    

    +33 (0)1 57 27 80 66, room 322B
  • 
    Aude-Isabelle DUPRE, Chercheur, WASSMANN LAB
    

    +33 (0)1 57 27 80 35, room 322B
  • 
    Safia EL JAILANI, Doctorante, WASSMANN LAB
    

    +33 (0)1 57 27 80 66, room 322B
  • 
    Emmanuelle MARJAULT, Doctorante, WASSMANN LAB
    

    +33 (0)1 57 27 80 66, room 322B
  • 
    Irem POLAT, Doctorante, WASSMANN LAB
    

    +33 (0)1 57 27 80 66, room 322B
  • 
    Sandra TOUATI, Chercheur, WASSMANN LAB
    

    +33 (0)1 57 27 80 35, room 322B