Created 28/11/2017 Updated 10/06/2018

We study the molecular mechanisms linking translational regulation to the control of cell cycle and embryonic development using mainly the sea urchin embryo as a model.

  

Unfertilized sea urchin eggs are haploid cells arrested after completion of their meiotic divisions at the G1 stage of the cell cycle. Translation activity is mainly repressed in unfertilized eggs, and increases after fertilization, independently of mRNA transcription and ribosome biogenesis. De novo protein synthesis is required for cell cycle progression. All known factors involved in translation are present. Several translational initiation and elongation factors are activated at fertilization, and are involved in the protein synthesis increase. For example amongst the prominent results, the translation of cyclin B, a key regulator of cell cycle progression, was shown to be highly dependent on the availability of the eIF4E translation factor, and on the mTOR pathway. We also demonstrated a new role of the MAP kinase pathway implicated in an early step of chromatin/microtubule attachment during mitosis progression after fertilization. Furthermore, our data revealed the existence of a new cell cycle checkpoint involving the translational inhibitor 4E-BP. De novo protein synthesis triggered by fertilization is dependent on stored maternal mRNAs. We have developed polysome profiling in sea urchin embryo (6), to identify cellular mRNA(s) whose translational status is (are) modified following fertilization. We showed that only a restricted subset of maternal mRNAs is translated after fertilization, encoding proteins involved in regulatory pathways; moreover, the mTOR pathway plays a differential role in the translation of specific mRNAs. These data suggest for the first time the existence of an alternative to the cap-dependent translation in response to fertilization, and that this alternative translation could be involved in proper progression of the cell cycle after fertilization. We develop functional, structural and system biology approaches to study translational control at fertilization at both translational level (the translational machinery) and post‐translational level (signaling kinases).

            In addition to the sea urchin model, we aim to identify new translational controls by analyzing marine multicellular organisms in several phyla of the tree of life (metazoans and macroalgae). These comparative approaches in distantly related phyla will enable the discovery of translational mechanisms that derive from innovation in specific lines or that correspond to development and/or conservation of ancestral mechanisms.      

Chassé H., Aubert J., Boulben S., Le Corguillé G., Corre E., Cormier P., Morales J. (2018) Translatome analysis at the egg-to-embryo transition in sea urchin. Nucleic Acids Research, 46(9), 4607–4621.  doi: 10.1093/nar/gky258

Cormier P. (2017) Translation regulator ballet in meiotic spindle. Cell Cycle (Invitation News and Views) doi: 10.1080/15384101.2017.1304732.

Chassé H., Boulben S., Costache V., Cormier P., Morales J. (2017) Analysis of translation using polysome profiling. Nucleic Acids Res. 45(3):e15 doi: 10.1093/nar/gkw907

Mulner-Lorillon O., Chassé H., Morales J., Bellé R., Cormier P. (2017) MAPK/ERK activity is required for the successful progression in mitosis in sea urchin embryos. Dev. Biol. 421(2):194-203 doi: 10.1016/j.ydbio.2016.11.018.

Cormier P., Chassé H., Cosson B., Mulner-Lorillon O., Morales J. (2016) Translational control in echinoderms: the calm before the storm. In « Evolution of the Protein Synthesis Machinery and its regulation » (Springer publishers). Editors: R. Jagus and G. Hernández. pp.413-434 DOI:10.1007/978-3-319-39468-8_16.

Chassé H, Mulner-Lorillon O, Boulben S, Glippa V, Morales J, Cormier P. (2016)  Cyclin B Translation Depends on mTOR Activity after Fertilization in Sea Urchin Embryos. PLoS One. 10; 11(3): e0150318. doi: 10.1371/journal.pone.0150318.

Picard V, Mulner-Lorillon O, Bourdon J, Morales J, Cormier P, Siegel A and Belle R. (2016) Model of the delayed translation of cyclin B maternal mRNA after sea urchin fertilization. Mol Reprod Dev doi: 10.1002/mrd.22746.