Evolution and Development of Germ Cells
Principal Investigator: Jean-René HUYNH, DR2 CnrsLaboratory website
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 ring canals. 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. Our lab has taken a forward genetic strategy to find the genes regulating these different processes. We have mutagenized randomly the genome and generated mutant lines, which are defective in the formation of the germline. Based on this collection of mutants, we 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. We found that specialized mechanisms are involved.
2) How is the duration of cytokinesis regulated in germ cells? We identified mutations in DrosophilaAurora-B and Cyclin-B genes, which regulate complete abscission in germline stem cells and incomplete abscission in differentiating germ cells.
3) How do homologue chromosomes find each other during meiosis? We 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. We are studying how mobile DNA elements such as transposons are silenced in germline cells.
- Mathieu, J., Michel-Hissier, P., Boucherit, V., and Huynh, J.-R. (2022). The deubiquitinase USP8 targets ESCRT-III to promote incomplete cell division. Science 376, 818–823.
- Molla Herman, A., and Brasset, E. (2021). Rhino breaks the deadlock in Drosophila testis. PLoS Genet 17, e1009702.
- Molla-Herman, A., Angelova, M.T., Ginestet, M., Carré, C., Antoniewski, C., and Huynh, J.-R. (2020). tRNA Fragments Populations Analysis in Mutants Affecting tRNAs Processing and tRNA Methylation. Front Genet 11, 518949.
- Chanet, S., and Huynh, J.-R. (2020). Collective Cell Sorting Requires Contractile Cortical Waves in Germline Cells. Curr. Biol.
- Rubin, T., Macaisne, N., and Huynh, J.-R. (2020). Mixing and Matching Chromosomes during Female Meiosis. Cells 9.
- Vallés, A.M., and Huynh, J.-R. (2020). Isolation of stage-specific germ cells using FACS in Drosophila germarium. Methods Cell Biol. 158, 11–24.
- Hatkevich, T., Boudreau, V., Rubin, T., Maddox, P.S., Huynh, J.-R., and Sekelsky, J. (2019). Centromeric SMC1 promotes centromere clustering and stabilizes meiotic homolog pairing. PLoS Genet. 15, e1008412.
- Nicolas Christophorou, Thomas Rubin, Isabelle Bonnet, Marion Arnaud and Jean-René Huynh: Microtubule-driven nuclear rotations promote meiotic chromosome dynamics. Nature Cell Biology 2015 Oct 12.
- Anahi Molla-Herman, Ana Maria Vallés, Carine Ganem-Elbaz, Christophe Antoniewski and Jean-René Huynh: tRNA processing defects induce replication stress and Chk2-dependent disruption of piRNA transcription. the EMBO journal, 2015, Oct 15. pii: e201591006.
- Juliette Mathieu, Clara Moch, Sarah J. Radford, Paola Sampaio, Carolina Perdigoto, François Schweisguth, Allison Bardin, Claudio Sunkel, Kim McKim and Jean-René Huynh: Aurora B and cyclin B have opposite effects on the timing of cytokinesis abscission in Drosophila germ cells and in vertebrate somatic cells. Developmental Cell, 2013 Aug 12;26(3):250-65.
- Pierre Fichelson, Clara Moch, Kenzo Ivanovitch, Charlotte Martin , Clara M Sidor, Jean-Antoine Lepesant, Yohanns Bellaiche and Jean-René Huynh: Live-imaging of single stem cells within their niche reveals that a U3snoRNP component segregates asymmetrically and is required for self-renewal in Drosophila. Nature Cell Biology 2009, June: 11(6) 685-93.
- Bécam I. E., G. Tanentzpaf, J.-A. Lepesant, N. H. Brown and Jean-René Huynh: Integrin-independent repression of cadherin transcription by talin during axis formation in Drosophila. Nature Cell Biology 2005, May;7(5):510-6.
Huynh Jean-René, DR2 CNRS
Mathieu Juliette, CRCN CNRS
Rubin Thomas, CRCN INSERM
Molla-Herman Anahi, CRCN CNRS
Chanet Soline, CRCN CNRS
Postdoctoral fellows, PhD Students:
Munro Catriona, Postdoctoral fellow
Ginestet Maud, PhD student
Boucherit Virginie IE CDD CDF
Cadis-guillon Hugo, IE CDD CDF
Thauvin Marion, IE CDD CDF