Understanding how germ cells develop is not only of paramount medical interest for reproductive medicine, but is also crucial to comprehend how animal shapes and forms evolve through generations. Jean-René Huynh and his team are focusing on how genetic information (through meiosis) and epigenetic information (through small RNAs) are transmitted to the next generation.
Germ cells are the only cells which are transmitted from one generation to the next and can be considered immortal. Germ cells produce highly specialized cells, called gametes, which carry the genetic and cytoplasmic information defining a given species and which can initiate the formation of an entire organism. Understanding how germ cells develop is not only of paramount medical interest for reproductive medicine, but is also crucial to comprehend how animal shapes and forms evolve through generations. Drosophila adult females present several key advantages as a model system to study germ cell development. In each ovary, there are germline stem cells (GSCs), which produce eggs (the female gamete) throughout the female life. It is thus possible to follow the entire development of germ cells from stem cell to fertilized egg in a single fly. Drosophila geneticists also keep on generating ever-more refined tools to control the function of every gene in the genome. It is for example possible to switch off one specific gene in germ cells at one precise time.
In females, GSCs are located at the anterior apex of a specialized structure called the germarium. GSCs divide asymmetrically leading to the formation of a self-renewing GSC and a differentiating cystoblast. The cystoblast then undergoes four rounds of asymmetric divisions with incomplete cytokinesis, leading to the formation of a cyst of 16 germline cells interconnected by cytoplasmic bridges called . Only one cell becomes the egg and goes through meiosis, while the 15 remaining cells become polyploidy nurse cells. Despite representing an excellent model system to study stem cell biology, cell cycle control, meiosis, cell fate determination or cell polarity, the germarium remains poorly explored.
1/ Jean-René Huynh and this team proposed that ribosome biogenesis is an important parameter of stem cell homeostasis (Fichelson et al, 2009). These results were later confirmed and extended in other organisms and model systems (see Le Bouteiller et al. 2013 and Zhang, Q. et al , Science 2014).
2/ They uncovered a function for CyclinB-Cdk-1 during abscission, occurring after anaphase onset, when CycB was previously thought to be entirely degraded (Mathieu J, et al. 2013). Late functions for CycB are confirmed for nuclear envelop reformation (Afonso, O. et al.).
3/ It was widely accepted that homologous chromosomes were paired in every Drosophila cells. They showed that homologues were not paired in germline stem cells, and became paired during the mitotic divisions preceding the “official” entry in meiosis (Christophorou et al, 2013, et aussi Joyce et al., 2013 et Cahoon and Hawley, 2013).
Jean-René and his team has taken a forward genetic strategy to find the genes regulating stem cell development, cell cycle control cell fate determination and cell polarity. They have mutagenized randomly the genome and generated mutant lines, which are defective in the formation of the germline. Based on this collection of mutants, they address the following questions:
1/ How is germline stem cell growth regulated? GSCs divide actively and need to recover their initial volume/mass quickly after each division. Jean-René Huynh and his team found that specialized mechanisms are involved.
2/ How is the number of germ cell divisions limited to four in the germarium? They identified mutations in Drosophila Aurora-B and Cyclin-B genes, which increase or decrease the number of rounds of division.
3/ How do homologue chromosomes find each other during meiosis? They are studying the potential role of the cytoplasmic cytoskeleton in regulating chromosome organization during the early steps of meiosis in the germarium.
4/ How is the germline genetic material protected from DNA damages? The genetic information contained in the female gamete needs to be safely transmitted to the next generation. Jean-René Huyn and his group are studying how a novel class of non-coding small RNAs protects the genome from DNA transposons.
• 1995 : Admitted to the Ecole Normale Supérieure, Paris, France
• 2003 : Ph. D. in Genetics, University of Cambridge, United Kingdom, Daniel St Johnston’s lab
• 2004 : Appointed Research scientist (CNRS, permanent position), Institut Jacques Monod, Paris, France, Jean-Antoine Lepesant's lab
• 2008 : Appointed Group leader at the Curie Institute, Paris, France
• 2017 : Senior position at Collège de France
• Main Prize, Ville de Paris 2009-2013
• Bronze Medal (Best Young Researchers), CNRS, 2007
Nov 2015, Nat Cell Biol
Dec 2013, PLoS Genet
May 2005, Nat. Cell Biol