Abstract The capacity to resume meiosis is progressively acquired during oogenesis and is ultimately restricted to fully grown oocytes. Meiotic resumption is triggered by hormonal stimulation and requires activation of Cdk1, the universal driver of M-phase entry. Cdk1 activation occurs in two steps: an initial activation of Cdk1, followed by an amplification phase that drives cell cycle re-entry. The first step depends on the accumulation of proteins that promote Cdk1 activation, while the second step involves a regulatory network of kinases and phosphatases. Using TMT-based quantitative proteomics, we reveal that growing oocytes first acquire the ability to regulate protein homeostasis in response to hormonal stimulation, and only later gain the competence to amplify initial Cdk1 activity and enter meiosis. Notably, protein accumulation, occurring independently of Cdk1 activation, is controlled by both translational and non-translational mechanisms. Together, our findings show that the molecular competence to trigger Cdk1 activation is acquired in a stepwise manner during oocyte growth. The earliest regulatory layer is the acquisition of the ability to respond to hormonal stimulation by accumulating proteins that are required for efficient Cdk1 activation and meiotic resumption.

Oocyte meiotic divisions represent a critical process in sexual reproduction, as a diploid non-dividing oocyte is transformed into a haploid fertilizable egg, as a prelude for the subsequent embryonic divisions and differentiation. Although cell differentiation and proliferation are governed by transcription, oocyte maturation and early embryonic divisions depend entirely on changes in protein abundance and post-translational modifications. Here, we analyze the abundance and phosphorylation of proteins during Xenopus oocyte meiotic maturation. We reveal significant shifts in protein stability, related to spindle assembly, DNA replication, and RNA-binding. Our analysis pinpoints broad changes in phosphorylation correlating with key cytological meiotic milestones, noteworthy changes in membrane trafficking, nuclear envelope disassembly, and modifications in microtubule dynamics. Additionally, specific phosphorylation events target regulators of protein translation, Cdk1 and the Mos/MAPK pathway, thereby providing insight into the dynamics of Cdk1 activity, as related to the meiotic cell cycle. This study sheds light on the orchestration of protein dynamics and phosphorylation events during oocyte meiotic divisions, providing a rich resource for understanding the molecular pathways orchestrating meiotic progression in the frog, and most likely applicable to other vertebrate species.

In 1830, Cuvier and Geoffroy Saint-Hilaire confronted each other in a famous debate on the unity of the animal kingdom, which permeated the zoology of the 19th century. From that time, a growing number of naturalists attempted to understand the large-scale relationships among animals. And among all the questions, that of the origin of vertebrates was one of the most controversial. Analytical methods based on comparative anatomy, embryology and paleontology were developed to identify convincing homologies that would reveal a logical sequence of events for the evolution of an invertebrate into the first vertebrate. Within this context, several theories have clashed on the question of the identity of the ancestor of vertebrates. Among the proposals, a group of rather discrete organisms, the ascidians, played a central role. Because he had discovered an ascidian with a particularly atypical larval development, the Molgula, Henri de Lacaze-Duthiers, a rigorous and meticulous naturalist, became involved in the ascidian hypothesis. While the visionary mind of Lacaze-Duthiers led him to establish a particularly innovative methodology and the first marine biology station in Europe, at Roscoff, the tailless tadpole of the Molgula prevented him from recognizing the ancestor of vertebrates. This old 19th century story echoes the ever-present questions driving the field of Eco-Evo-Devo.

Édouard Chatton (1883Édouard Chatton ( -1947) ) est un biologiste majeur de la première moitié du 20 e siècle qui a consacré sa vie à l'étude des êtres microscopiques qui peuplent toutes les eaux de la planète, les protistes.D'abord chercheur à l'Institut Pasteur, il est ensuite professeur des universités à Strasbourg, à Montpellier et à la Sorbonne.Il dirige les stations marines de Sète puis de Banyuls-sur-Mer.Il accumule les découvertes qui fondent la biologie cellulaire moderne et conceptualise la distinction du monde vivant entre procaryotes et eucaryotes.Ses figures scientifiques révèlent son remarquable talent de dessinateur et de coloriste.Édouard Chatton est aussi peintre amateur, maîtrisant avec dextérité la peinture à l'huile, l'aquarelle et le pastel.La recherche artistique du peintre influe-t-elle sur les illustrations scientifiques réalisées par le chercheur ?Les objets d'études du scientifique irriguent-ils la démarche esthétique du peintre ?Si les deux types de pratique, dessins scientifiques et tableaux du peintre amateur, ne semblent pas s'interpénétrer, il est un troisième type de réalisation beaucoup plus troublant.Il s'agit de grandes planches cartonnées recouvertes de dessins, destinées à illustrer les cours d'Édouard Chatton en amphithéâtre.Ces planches, harmonieuses, colorées de façon surprenante, emplies de formes ondulantes, étranges et énigmatiques, sont chargées d'une merveilleuse beauté et dégagent une séduction esthétique immédiate.Les découvrir est une occasion originale d'aborder la question de la convergence entre art et science.ABSTRACT.Édouard Chatton (1883-1947) was a major biologist of the first half of the 20 th century, who devoted his life to the study of the microscopic organisms that live in all waters of the planet, the protists.Initially a researcher at the Pasteur Institute, he became a professor at the universities of Strasbourg, Montpellier and the Sorbonne.He directed the marine stations at Sète and Banyuls-sur-Mer.His discoveries laid the foundations for modern cell biology, and he conceptualized the distinction between prokaryotes and eukaryotes in the living world.His scientific drawings reveal his remarkable talent as a draftsman and colorist.Édouard Chatton was also an amateur painter, mastering oil paint, watercolor and pastel.Did the painter's artistic eye influence the scientific illustrations produced by the researcher?Did the scientific objects of the biologist influence the painter's aesthetic approach?If the two types of practice -scientific drawings and paintings by the amateur painter -do not seem to interpenetrate, there is a third type of production that leaves room for questioning.These are large cardboard sheets covered with drawings, used to illustrate Édouard Chatton's amphitheater lectures.These harmonious, surprisingly colored boards, filled with undulating, strange and enigmatic shapes, are charged with marvelous beauty and exude an immediate aesthetic seduction.Discovering them is an original opportunity to tackle the question of the convergence between art and science.

cAMP-PKA signaling initiates the crucial process of oocyte meiotic maturation in many animals, but inhibits it in vertebrates. To address this 'cAMP paradox', we exchanged the key PKA substrate ARPP19 between representative species, the vertebrate Xenopus and the cnidarian Clytia, comparing its phosphorylation and function. We found that, as in Xenopus, Clytia maturing oocytes undergo ARPP19 phosphorylation on a highly conserved Gwl site, which inhibits PP2A and promotes M-phase entry. In contrast, despite a PKA phosphorylation signature motif recognizable across most animals, Clytia ARPP19 was only poorly phosphorylated by PKA in vitro and in vivo. Furthermore, unlike Xenopus ARPP19, exogenous Clytia ARPP19 did not delay Xenopus oocyte maturation. We conclude that, in Clytia, ARPP19 does not intervene in oocyte maturation initiation because of both poor recognition by PKA and the absence of effectors that mediate vertebrate oocyte prophase arrest. We propose that ancestral ARPP19 phosphorylated by Gwl has retained a key role in M-phase across eukaryotes and has acquired new functions during animal evolution mediated by enhanced PKA phosphorylation, allowing co-option into oocyte maturation regulation in the vertebrate lineage.

ABSTRACT In many animal species, elevated cAMP-PKA signaling initiates oocyte meiotic maturation upon hormonal stimulation, whereas in vertebrates, it acts as a negative regulator of this process. To address this “cAMP paradox”, we have focused on ARPP19 proteins. Dephosphorylation of Xenopus ARPP19 on a specific PKA site has been identified as a key step in initiating oocyte maturation. We first tracked evolution of the ARPP19 PKA phosphorylation site, revealing that it appeared early during the emergence of metazoans. This contrasts with strong conservation across eukaryotes of a phosphorylation site for the kinase Gwl in ARPP19 proteins, able to transform them into potent PP2A-B55 inhibitors and thus promote M-phase entry. We then compared the phosphorylation and function of Xenopus ARPP19 with its orthologue from the jellyfish Clytia , a model species showing cAMP-induced oocyte maturation. We confirmed that Clytia ARPP19 is phosphorylated on the conserved Gwl site in vitro as well as in maturing Xenopus and Clytia oocytes, behaving as a PP2A inhibitor and contributing to Cdk1 activation. However, Gwl-phosphorylated ARPP19 was unable to initiate oocyte maturation in Clytia , suggesting the presence of additional locks released by hormonal stimulation. Clytia ARPP19 was in vitro phosphorylated by PKA uniquely on the predicted site, but it was a much poorer substrate of PKA and of its antagonizing phosphatase, PP2A-B55δ, than the Xenopus protein. Correspondingly, PKA-phosphomimetic Clytia ARPP19 had a much weaker inhibitory activity on meiosis resumption in Xenopus oocytes than its Xenopus counterpart. Hence, poor recognition of Clytia ARPP19 by PKA and the absence of its targets in Clytia oocytes account for the cAMP paradox. This cross-species study of ARPP19 illustrates how initiation of oocyte maturation has complexified during animal evolution, and provides further insight into its biochemical regulation.

1872, France. An eminent zoologist of the time, Henri de Lacaze-Duthiers, realises one of his most important goals: he creates a new journal, focused on zoological discoveries, which he calls "Archives de Zoologie Experimentale et Generale". His motivations were threefold. The first was to participate in the intellectual reconstruction of France, humiliated by the defeat against Prussia in 1871. The second was to promote a new way of conceiving and doing zoology: zoology should be approached through experience (and not just observation), and it should be general, including everything related to animal life (embryology, physiology, histology, ecology). The third was to acquire freedom and autonomy by liberating himself from the conservative journal that had a quasi-monopoly on zoology at the time, "Les Annales de sciences naturelles". The Archives, which had a difficult start, had an impressive success, revealing young talents from all over Europe and reporting on major discoveries, until their last issue in 1981. This article recounts their adventure.

Présentation de Lucien Joliet et de Henri de Lacaze-Duthiers

Why revive, 200 years after his birth, the personality and work of the zoologist Henri de Lacaze-Duthiers (1821-1901)? Did his work have a lasting impact on research until today? In what way can his career enrich the scientists of today? His evocation should bring some answers to these questions. We will follow him from his youth in an austere castle in the southwest of France to Paris where his taste for natural sciences and his republican convictions are affirmed; then in his first scientific expeditions where his passion for the world of marine invertebrates is triggered. We will witness the progression of his scientific work nourished by his multiple trips to the coasts and his university career, from Lille to Paris. Once he reached academic consecration, we will see him conceptualize the refoundation of zoology into a reso-lutely experimental discipline, by proposing a corpus of pioneering methods. We will leave him as the builder of the first marine stations of Roscoff and Banyuls-sur-Mer which, until today, are at the heart of European marine biology.

À partir de 1873 et jusqu’en 1883, Henri de Lacaze-Duthiers, professeur de zoologie à la Sorbonne et membre de l’Institut, loue à Roscoff, à l’année, une « maison nouvelle » meublée située place de l’Église et propriété de Mme Rolland. Cette maison a constitué le noyau initial du laboratoire de zoologie expérimentale créé sur le papier, à Roscoff, le 20 août 1872.

Lorsque Lacaze-Duthiers est nommé professeur à la Sorbonne en 1869, il a consacré les seize années précédentes à des recherches approfondies sur divers invertébrés marins. Ces travaux l’ont conduit à élaborer une nouvelle méthode de pratique et d’enseignement de la zoologie. Jusqu’alors, scientifiques et étudiants observaient dans leur faculté, à la ville, des animaux morts, conservés dans l’alcool depuis parfois de longues années et souvent altérés par le temps et les liquides chimiques de conservation. Ils ne les avaient généralement jamais vus vivants et ignoraient leurs conditions de vie. Les sciences dites « de la vie » reposaient sur l’étude de collections d’êtres morts ! Des expéditions de terrain avaient néanmoins vu le jour au milieu du XIXe siècle sous l’impulsion notoire de Henri Milne-Edwards, directeur de thèse de Lacaze-Duthiers, dans le but d’observer des animaux vivants et dans leur milieu naturel.

Oocytes are held in meiotic prophase for prolonged periods until hormonal signals trigger meiotic divisions. Key players of M-phase entry are the opposing Cdk1 kinase and PP2A-B55δ phosphatase. In Xenopus, the protein Arpp19, phosphorylated at serine 67 by Greatwall, plays an essential role in inhibiting PP2A-B55δ, promoting Cdk1 activation. Furthermore, Arpp19 has an earlier role in maintaining the prophase arrest through a second serine (S109) phosphorylated by PKA. Prophase release, induced by progesterone, relies on Arpp19 dephosphorylation at S109, owing to an unknown phosphatase. Here, we identified this phosphatase as PP2A-B55δ. In prophase, PKA and PP2A-B55δ are simultaneously active, suggesting the presence of other important targets for both enzymes. The drop in PKA activity induced by progesterone enables PP2A-B55δ to dephosphorylate S109, unlocking the prophase block. Hence, PP2A-B55δ acts critically on Arpp19 on two distinct sites, opposing PKA and Greatwall to orchestrate the prophase release and M-phase entry.

On the occasion of the 200th anniversary of the birth of Henri de Lacaze-Duthiers, one of the most curious and active scientific minds among 19th century naturalists, this article retraces his scientific career and recalls the long-term changes he made in the practice of science: promotion of experimental zoology, foundation of a modern scientific journal and establishment of the marine stations of Roscoff and Banyuls.

The study of oocytes has made enormous contributions to the understanding of the G2/M transition. The complementarity of investigations carried out on various model organisms has led to the identification of the M-phase promoting factor (MPF) and to unravel the basis of cell cycle regulation. Thanks to the power of biochemical approaches offered by frog oocytes, this model has allowed to identify the core signaling components involved in the regulation of M-phase. A central emerging layer of regulation of cell division regards protein translation. Oocytes are a unique model to tackle this question as they accumulate large quantities of dormant mRNAs to be used during meiosis resumption and progression, as well as the cell divisions during early embryogenesis. Since these events occur in the absence of transcription, they require cascades of successive unmasking, translation, and discarding of these mRNAs, implying a fine regulation of the timing of specific translation. In the last years, the Xenopus genome has been sequenced and annotated, enabling the development of omics techniques in this model and starting its transition into the genomic era. This review has critically described how the different phases of meiosis are orchestrated by changes in gene expression. The physiological states of the oocyte have been described together with the molecular mechanisms that control the critical transitions during meiosis progression, highlighting the connection between translation control and meiosis dynamics.