Biology of the oocyte

Cells proliferate by means of the mitotic cell cycle, which underlies development, growth and maintenance in all living organisms. While the cell cycle has fascinated biologists for many years, unravelling the mechanisms that drive cell division is far from complete. M-phase entry is a switch-like transition orchestrated by phosphorylation of hundreds of proteins that govern the mechanics of cell division. These “mitotic substrates” are controlled by a cohort of kinases and phosphatases, themselves regulated by two master enzymes: the mitotic kinase Cdk1-Cyclin B (MPF for M-phase Promoting Factor) and its antagonizing phosphatase, PP2A. Since meiotic divisions use the same molecular players than mitosis, oocytes have been used as a historically important model system to study cell division.

Our work is dedicated to the understanding of the control of meiotic divisions by using the Xenopus oocyte as a model system. Oocytes are arrested in prophase of the 1st meiotic division, assimilated to a late G2 arrest. The release from the prophase block of frog oocytes is triggered by progesterone. This steroid induces a rapid decrease of the cAMP concentration and PKA activity, allowing de novo synthesis of Cyclin B1 and Mos kinase from stored mRNAs. These proteins lead to MPF activation, promoting the 1st meiotic division. MPF activity falls during anaphase I, due to partial Cyclin degradation, and rises again leading to entry into meiosis II. The oocyte arrests at metaphase II, because of the stabilization of MPF by Mos.

Our projects focus on several questions:

1. The role of the PKA substrate, Arpp19, in preventing M-phase entry;

2. Activating Cdk1 in meiosis: role of Arpp19 and deciphering the interactome of Cdk1-Cyclin B complexes;

3. Beyond Xenopus meiosis: Arpp19 as a master regulator in other models;

4. The translational control of meiotic divisions.


Read our review articles!

Meneau F, Dupré A, Jessus C and Daldello EM (2020) Translational control of Xenopus oocyte meiosis: toward the genomic era. Cells, 9, 1502. PMCID: PMC7348711 DOI: 10.3390/cells9061502

Lemonnier T, Dupré A and Jessus C (2020) The G2-to-M transition from a phosphatase perspective: a new vision of the meiotic division. Cell Division, 15, 9. PMCID: PMC7249327 DOI: 10.1186/s13008-020-00065-2

Jessus C, Munro C and Houliston E (2020) Managing the oocyte meiotic arrest-Lessons from frogs and jellyfish. Cells, 9, 1150. PMCID: PMC7290932 DOI: 10.3390/cells9051150

Dupré A and Jessus C (2017) The Yin and Yang of Arpp19 phosphorylation: arresting or releasing cell division in "Phosphorylation", Open Access Book, Edited by Dr Claude Prigent. InTechOpen Publisher.

Haccard O and Jessus C (2011) Greatwall kinase, Arpp19 and protein phosphatase 2A: shifting the mitosis paradigm. Chapter in "Cell Cycle in Development. Results Probl Cell Differ". Editor: J Kubiak, Springer Verlag Publishers. 53, pp.219-234. PMID: 21630148

Dupré A, Haccard O and Jessus C (2011) Mos in the oocyte: how to use MAPK independently of growth factors and transcription to control meiotic divisions. J. Signal. Transduc. 2011, 350-412. PMID: 21637374

Jessus C (2010) MPF and the control of meiotic divisions: old problems, new concepts. Chapter in "Oogenesis. The Universal process", Editors: MH Verlhac & A Villeneuve, Wiley-Blackwell Editions. pp 227-265.

Jessus C and Haccard O (2007) Calcium's double punch. Nature 449, 297-298. PMID: 17882212 DOI: 10.1038/449297a

Haccard O and Jessus C (2006) Oocyte maturation, Mos and cyclins; a matter of synthesis. Cell Cycle 5, 1152-1159. PMID: 16760654


The prophase arrest is controlled by a high activity of PKA. Meiosis resumption relies on a drop in PKA activity, hence the dephosphorylation of a critical PKA substrate. This step leads to the further activation of MPF and the Mos/MAPK cascade that induce the completion of meiotic division. Our recent results reveal that:

1. Arpp19 is the long sought PKA substrate controlling M-phase entry in Xenopus oocytes. Once phosphorylated by PKA at S109, it inhibits MPF activation and maintains the prophase block. Its dephosphorylation, which takes place within 30 min in response to progesterone stimulation, is needed to overcome this blockade (Dupré et al, Nature Commun, 2014).

2. We recently discovered that the phosphatase that antagonizes PKA by dephosphorylating Arpp19 at S109 corresponds to PP2A-B55delta (Lemonnier et al, Cell Division, 2020; Lemonnier et al, Nature Commun, 2021).

3. At the time of MPF activation, several hours after hormonal stimulation, PP2A-B55delta, Gwl and Arpp19 are pivotal effectors within the Cdk1 auto-regulatory loop (Dupré et al, Cell Cycle, 2017; Dupré et al, J Cell Sci, 2013).

Therefore, Arpp19 and PP2A-B55delta play a dual role in the oocyte at both extremities of the signalling cascade leading to MPF activation: they control the starting point as well as the Cdk1 final point, active PP2A-B55delta dephosphorylating Arpp19 at S109 at the beginning, and being inhibited by S67-phosphorylated Arpp19 at the end.

Future directions

The mechanisms underlying entry into M-phase are still ill-defined. Based on the conserved nature of cell cycle components and since meiotic and mitotic divisions share identical molecular players, we use a powerful physiological model system, oocyte meiotic maturation, to cover this lack of knowledge.

Our project focuses on 4 questions:

  • The role of Arpp19 in preventing M-phase entry. We are identifying by mass spectrometry the partners of Arpp19 under its various phosphorylated forms. The function of these new partners as transducers of Arpp19 inhibitory effects towards Cdk1 are addressed by combining expression or inhibition of these proteins in Xenopus oocytes.
  • Activating Cdk1 during meiosis: role of Arpp19 and deciphering the interactome of Cdk1-Cyclin B complexes. The active form of Arpp19 that sustains Cdk1 activation is not uniquely phosphorylated at S67, but is also phosphorylated at S109. We are deciphering the positive control exerted by S109-S67-phosphorylated Arpp19 on meiotic divisions. We also discovered that Cdk1-Cyclin B dimers are included into large molecular weight complexes, suggesting that MPF would not be the canonical Cdk1-Cyclin B dimer but a much larger complex including unknown partners. We carry an in-deep biochemical analysis of Cdk1-containing complexes in order to get an exhaustive knowledge of the protein partners of Cdk1, their dynamics and their roles in the activation of Cdk1.
  • Beyond Xenopus meiosis: Arpp19 as a master regulator in other species? In some invertebrates, such as the jellyfish, meiosis resumption works in a reverse way compared to vertebrates, PKA requiring to be activated for further Cdk1 activation to occur (Jessus et al, Cells, 2020). In collaboration with the group of Evelyn Houliston, we aim at understanding how Arpp19 is positioned in this paradoxical effect of PKA on the resumption of meiosis.
  • The translational control of meiotic divisions. During meiotic maturation, transcription is mostly silent. In most vertebrates, except small rodents, protein synthesis is required for MPF activation (Meneau et al, Cells, 2020). We study the role and the regulation of mRNA translation during meiotic maturation: identification and functions of de novo translated mRNAs, control of their translation (cis-acting elements and new RNA-binding proteins).