We study how protein phosphorylation participates in the molecular control of early development.
The fusion of gametes at fertilization reconstitutes a cell with a diploid complement of chromosomes. Afterwards, this new zygote undergoes a rapid series of cell divisions followed by cell differentiations and migrations that lead to embryo formation. These events are initially controlled by maternal determinants that will be replaced progressively by proteins transcribed from zygotic DNA. The proteins shaping the new embryo are the object of continuous phosphorylation/dephosphorylation steps which orchestrate precisely their respective activities. The team investigates how these post-traductional modifications, and more precisely those due to the cyclin dependent kinases (CDKs), fit into the regulatory mechanisms controlling early development.
The model organism for these studies is the Sea urchin. Sea urchins are simple marine invertebrates that develop rapidly from eggs to swimming and feeding larvae. These echinoderms produce large amounts of gametes which give rise, after in vitro fertilization, to synchronously developing, transparent embryos. These properties facilitate biochemical and cell biology experiments, and the already sequenced genomes of the local species Paracentrotus lividus allows genomic and proteomic approaches. In addition, sea urchin oocytes are fertilized after completion of meiosis, in a haploid state (G1 phase) thus the first mitotic cell cycle is directly initiated, beginning by zygotic DNA replication.
The team studies how this first DNA replication is initiated and how CDKs control this cell cycle re-initiation. CDKs are not only critical cell cycle regulators they also control gene expression. In sea urchins, the transition toward zygotic gene expression progressively takes place in the blastula. The team uncovered in sea urchin a new CDK, CDK13, which is conserved in vertebrates and where it participates in the regulation of pre-mRNAs constitutive and alternative splicing. Its role during development is currently being investigated in P. lividus.