Institut Jacques Monod
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Polarity and Morphogenesis

Antoine GUICHET

Our research team aims to elucidate the molecular mechanisms that control cell polarity and tissue morphogenesis in relation with the cytoskeleton and in particular with the microtubule network.

Keywords: Cell polarity, morphogenesis, microtubules, asymmetric transport, phospholipids, PAR protein complexes

+33 (0)157278076     antoine.guichet(at)ijm.fr     @GuichetLab

Research

The understanding of the mechanisms, which orchestrate tissue and organ formation and which control their architecture maintenance, is a fundamental question in biology. Tissue formation and associated homeostasis are coordinated through cellular processes that include cell polarity, cell adhesion and motility. The understanding of these processes is also essential to better understand the molecular mechanisms controlling the development of pathologies such as cancer.

Our research team aims to elucidate the molecular mechanisms that control cell polarity and tissue morphogenesis in relation with the cytoskeleton and in particular with the microtubule network. To do so we are using Drosophila development as model system and we focus our research especially on two axes.

  1. At a cellular level, by exploring cytoskeleton requirement for the oocyte polarity establishment during oogenesis. We are investigating the molecular mechanisms involved in protein and mRNA asymmetric transport and those required for the asymmetric positioning of the nucleus.
  2. At a tissue level, by studying cytoskeleton requirement in tissue morphogenesis. We are looking for the molecular processes controlling collective cell migration required for the establishment of the reparatory system during embryogenesis.

We are using both conventional and innovative methodologies by combining genetic, biophysics and cell biology technics. Furthermore, live imaging associated with advanced light microscopy and electron microscopy are the core our experiments.

Nuclear migration in the Drosophila oocyte

Membrane organisation in the Drosophila oocyte

Collective migration of tracheal
cells in the Drosophila embryo

 

The research topics of the team:

* Identification of mechanisms controlling the asymmetric positioning of the nucleus in the oocyte.

* Identification and characterisation of the different microtubule networks required for the oocyte polarisation.

* Relationship between the lipid domains connected to phosphatidylinositol(4,5) biphosphate and the polarity proteins in the intracellular organisation and the polarized transport.

* Characterisation of the cytoskeleton requirement, microtubules and actin, in the collective cell migration process controlling the formation of the tracheal branches in the embryo.

 

Nuclear migration in the Drosophila oocyte

 

Membrane organisation in the Drosophila oocyte

Collective migration of tracheal cells in the Drosophila embryo

Members

Group Leader:

Antoine GUICHET
Phone : +33 (0)157278076, +33 (0)157278087
Email : antoine.guichet(at)ijm.fr

 

Members:

Frédéric BERNARD Researcher
Véronique BRODU Researcher
Sylvain BRUN Researcher
Sandra CLARET Researcher
Jean-Antoine LEPESANT Emeritus Researcher
Sandra CARVALHO PhD Student
Fanny ROLAND GOSSELIN PhD Student
Joanna AOUAD Master 2
Nicolas ROBERT Master 2
Marie Caroline VIRON Master 2

Selected Publications

The Importance of the Position of the Nucleus in Drosophila Oocyte Development. Lepesant JA, Roland-Gosselin F, Guillemet C, Bernard F, Guichet A. Cells. (2024)

 

Kinesin-1 promotes centrosome clustering and nuclear migration in the Drosophila oocyte. Development. Loh, M., Bernard, F., Guichet, A. (2023).

 

Dynein-mediated transport and membrane trafficking control PAR3 polarised distribution. Jouette J, Guichet A, Claret S. eLIFE (2019)

 

Distinct molecular cues ensure a robust microtubule-dependent nuclear positioning in the Drosophila oocyte.Tissot N, Lepesant JA, Bernard F, Legent K, Bosveld F, Martin C, Faklaris O, Bellaïche Y, Coppey M, Guichet A. Nature Communication. (2017)

 

Microtubule-dependent apical restriction of recycling endosomes sustains adherens junctions during morphogenesis of the Drosophila tracheal system. Le Droguen PM, Claret S, Guichet A, Brodu V. Development. (2015)

 

PI(4,5)P2 produced by the PI4P5K Skittles controls the apical domain size by tethering PAR-3 in Drosophila epithelial cells. Claret S, Benoit B, Richard-Ferrec G, Guichet A, Current Biology. (2014)

 

A developmentally regulated two-step process generates a non-centrosomal microtubule network. Brodu V, Baffet A, Le Droguen PM, Casanova J, Guichet A. Developmental Cell . (2010)

 

PIP5K-dependent production of PIP2 sustains microtubule organization to establish polarized transport in the Drosophila oocyte. Gervais L, Claret S, Januschke J, Roth S, Guichet A. Development (2008).

 

The Centrosome Nucleus complex directs the formation of two orthogonal microtubule polarized transport in the Drosophila oocyte Januschke J, Gervais L, Gillet, L., Keryer G, Bornen M, Guichet A. Development. (2006).

 

Polar transport in the Drosophila oocyte requires Dynein and Kinesin I cooperation, Januschke J, Gervais L, Dass S, Kaltschmidt J, Lopez-Schier H, St. Johnston D, Brand A, Roth S and Guichet A. Current Biology (2002).

All the publications

Publications 

Mallart, C., Netter, S., Chalvet, F., Claret, S., Guichet, A., Montagne, J., Pret, A.-M., & Malartre, M. (2024). JAK-STAT-dependent contact between follicle cells and the oocyte controls Drosophila anterior-posterior polarity and germline development. Nature Communications, 15(1), 1627. https://doi.org/10.1038/s41467-024-45963-z
Lepesant, J.-A., Roland-Gosselin, F., Guillemet, C., Bernard, F., & Guichet, A. (2024). The Importance of the Position of the Nucleus in Drosophila Oocyte Development. Cells, 13(2), 201. https://doi.org/10.3390/cells13020201
Zhu, Z., Becam, I., Tovey, C. A., Elfarkouchi, A., Yen, E. C., Bernard, F., Guichet, A., & Conduit, P. T. (2023). Multifaceted modes of γ-tubulin complex recruitment and microtubule nucleation at mitotic centrosomes. Journal of Cell Biology, 222(10), e202212043. https://doi.org/10.1083/jcb.202212043
Loh, M., Bernard, F., & Guichet, A. (2023). Kinesin-1 promotes centrosome clustering and nuclear migration in the Drosophila oocyte. Development, dev.201728. https://doi.org/10.1242/dev.201728
Galenza, A., Moreno-Roman, P., Su, Y.-H., Acosta-Alvarez, L., Debec, A., Guichet, A., Knapp, J.-M., Kizilyaprak, C., Humbel, B. M., Kolotuev, I., & O’Brien, L. E. (2023). Basal stem cell progeny establish their apical surface in a junctional niche during turnover of an adult barrier epithelium. Nature Cell Biology. https://doi.org/10.1038/s41556-023-01116-w
Tovey, C. A., Tsuji, C., Egerton, A., Bernard, F., Guichet, A., de la Roche, M., & Conduit, P. T. (2021). Autoinhibition of Cnn binding to γ-TuRCs prevents ectopic microtubule nucleation and cell division defects. The Journal of Cell Biology, 220(8), e202010020. https://doi.org/10.1083/jcb.202010020
Loh, M., Guichet, A., & Bernard, F. (2021). Nuclear Migration in the Drosophila Oocyte. JoVE (Journal of Visualized Experiments), 171, e62688. https://doi.org/10.3791/62688
Bernard, F., Jouette, J., Durieu, C., Le Borgne, R., Guichet, A., & Claret, S. (2021). GFP-Tagged Protein Detection by Electron Microscopy Using a GBP-APEX Tool in Drosophila. Frontiers in Cell and Developmental Biology, 9. https://www.frontiersin.org/articles/10.3389/fcell.2021.719582
Mukherjee, A., Brooks, P. S., Bernard, F., Guichet, A., & Conduit, P. T. (2020). Microtubules originate asymmetrically at the somatic golgi and are guided via Kinesin2 to maintain polarity within neurons. ELife, 9, e58943. https://doi.org/10.7554/eLife.58943
Métivier, M., Monroy, B. Y., Gallaud, E., Caous, R., Pascal, A., Richard-Parpaillon, L., Guichet, A., Ori-McKenney, K. M., & Giet, R. (2019). Dual control of Kinesin-1 recruitment to microtubules by Ensconsin in Drosophila neuroblasts and oocytes. Development (Cambridge, England), 146(8), dev171579. https://doi.org/10.1242/dev.171579
Jouette, J., Guichet, A., & Claret, S. B. (2019). Dynein-mediated transport and membrane trafficking control PAR3 polarised distribution. ELife, 8, e40212. https://doi.org/10.7554/eLife.40212
Bernard, F., Lepesant, J.-A., & Guichet, A. (2018). Nucleus positioning within Drosophila egg chamber. Seminars in Cell & Developmental Biology, 82, 25–33. https://doi.org/10.1016/j.semcdb.2017.10.013
Tissot, N., Lepesant, J.-A., Bernard, F., Legent, K., Bosveld, F., Martin, C., Faklaris, O., Bellaïche, Y., Coppey, M., & Guichet, A. (2017). Distinct molecular cues ensure a robust microtubule-dependent nuclear positioning in the Drosophila oocyte. Nature Communications, 8(1), 15168. https://doi.org/10.1038/ncomms15168
White, P. M., Serbus, L. R., Debec, A., Codina, A., Bray, W., Guichet, A., Lokey, R. S., & Sullivan, W. (2017). Reliance of Wolbachia on High Rates of Host Proteolysis Revealed by a Genome-Wide RNAi Screen of Drosophila Cells. Genetics, 205(4), 1473–1488. https://doi.org/10.1534/genetics.116.198903
Jouette, J., Claret, S., & Guichet, A. (2017). Phosphoinositides and Cell Polarity in the Drosophila Egg Chamber. In M. Kloc (Ed.), Oocytes: Maternal Information and Functions (pp. 169–187). Springer International Publishing. https://doi.org/10.1007/978-3-319-60855-6_8
Debec, A., Megraw, T. L., & Guichet, A. (2016). Methods to Establish Drosophila Cell Lines. In C. Dahmann (Ed.), Drosophila: Methods and Protocols (pp. 333–351). Springer. https://doi.org/10.1007/978-1-4939-6371-3_21
Le Droguen, P.-M., Claret, S., Guichet, A., & Brodu, V. (2015). Microtubule-dependent apical restriction of recycling endosomes sustains adherens junctions during morphogenesis of the Drosophila tracheal system. Development, 142(2), 363–374. https://doi.org/10.1242/dev.113472
Legent, K., Tissot, N., & Guichet, A. (2015). Visualizing Microtubule Networks During Drosophila Oogenesis Using Fixed and Live Imaging. In D. P. Bratu & G. P. McNeil (Eds.), Drosophila Oogenesis: Methods and Protocols (pp. 99–112). Springer. https://doi.org/10.1007/978-1-4939-2851-4_7
Claret, S., Jouette, J., Benoit, B., Legent, K., & Guichet, A. (2014). PI(4,5)P2 Produced by the PI4P5K SKTL Controls Apical Size by Tethering PAR-3 in Drosophila Epithelial Cells. Current Biology, 24(10), 1071–1079. https://doi.org/10.1016/j.cub.2014.03.056
Lecland, N., Debec, A., Delmas, A., Moutinho-Pereira, S., Malmanche, N., Bouissou, A., Dupré, C., Jourdan, A., Raynaud-Messina, B., Maiato, H., & Guichet, A. (2013). Establishment and mitotic characterization of new Drosophila acentriolar cell lines from DSas-4 mutant. Biology Open, 2(3), 314–323. https://doi.org/10.1242/bio.20133327
Baffet, A. D., Benoit, B., Januschke, J., Audo, J., Gourhand, V., Roth, S., & Guichet, A. (2012). Drosophila tubulin-binding cofactor B is required for microtubule network formation and for cell polarity. Molecular Biology of the Cell, 23(18), 3591–3601. https://doi.org/10.1091/mbc.e11-07-0633
Parrott, B. B., Chiang, Y., Hudson, A., Sarkar, A., Guichet, A., & Schulz, C. (2011). Nucleoporin98-96 Function Is Required for Transit Amplification Divisions in the Germ Line of Drosophila melanogaster. PLOS ONE, 6(9), e25087. https://doi.org/10.1371/journal.pone.0025087
Brodu, V., Baffet, A. D., Le Droguen, P.-M., Casanova, J., & Guichet, A. (2010). A Developmentally Regulated Two-Step Process Generates a Noncentrosomal Microtubule Network in Drosophila Tracheal Cells. Developmental Cell, 18(5), 790–801. https://doi.org/10.1016/j.devcel.2010.03.015
Fabian, L., Wei, H.-C., Rollins, J., Noguchi, T., Blankenship, J. T., Bellamkonda, K., Polevoy, G., Gervais, L., Guichet, A., Fuller, M. T., & Brill, J. A. (2010). Phosphatidylinositol 4,5-bisphosphate Directs Spermatid Cell Polarity and Exocyst Localization in Drosophila. Molecular Biology of the Cell, 21(9), 1546–1555. https://doi.org/10.1091/mbc.e09-07-0582
Lachkar, S., Lebois, M., Steinmetz, M. O., Guichet, A., Lal, N., Curmi, P. A., Sobel, A., & Ozon, S. (2010). Drosophila Stathmins Bind Tubulin Heterodimers with High and Variable Stoichiometries. The Journal of Biological Chemistry, 285(15), 11667–11680. https://doi.org/10.1074/jbc.M109.096727
Compagnon, J., Gervais, L., Roman, M. S., Chamot-Bœuf, S., & Guichet, A. (2009). Interplay between Rab5 and PtdIns(4,5)P2 controls early endocytosis in the Drosophila germline. Journal of Cell Science, 122(1), 25–35. https://doi.org/10.1242/jcs.033027
Nicolas, E., Chenouard, N., Olivo-Marin, J.-C., & Guichet, A. (2009). A Dual Role for Actin and Microtubule Cytoskeleton in the Transport of Golgi Units from the Nurse Cells to the Oocyte Across Ring Canals. Molecular Biology of the Cell, 20(1), 556–568. https://doi.org/10.1091/mbc.e08-04-0360
Gervais, L., Claret, S., Januschke, J., Roth, S., & Guichet, A. (2008). PIP5K-dependent production of PIP2 sustains microtubule organization to establish polarized transport in the Drosophila oocyte. Development, 135(23), 3829–3838. https://doi.org/10.1242/dev.029009
Januschke, J., Nicolas, E., Compagnon, J., Formstecher, E., Goud, B., & Guichet, A. (2007). Rab6 and the secretory pathway affect oocyte polarity in Drosophila. Development, 134(19), 3419–3425. https://doi.org/10.1242/dev.008078
GUICHET, A. (2007). Mise en place de la polarité au sein de l’ovocyte de drosophile : (R)évolution du développement. Mise En Place de La Polarité Au Sein de l’ovocyte de Drosophile : (R)Évolution Du Développement, 281, 24–27.
Januschke, J., Gervais, L., Gillet, L., Keryer, G., Bornens, M., & Guichet, A. (2006). The centrosome-nucleus complex and microtubule organization in the Drosophila oocyte. Development, 133(1), 129–139. https://doi.org/10.1242/dev.02179
Januschke, J., Gervais, L., Dass, S., Kaltschmidt, J. A., Lopez-Schier, H., Johnston, D. St., Brand, A. H., Roth, S., & Guichet, A. (2002). Polar Transport in the Drosophila Oocyte Requires Dynein and Kinesin I Cooperation. Current Biology, 12(23), 1971–1981. https://doi.org/10.1016/S0960-9822(02)01302-7
Tazuke, S. I., Schulz, C., Gilboa, L., Fogarty, M., Mahowald, A. P., Guichet, A., Ephrussi, A., Wood, C. G., Lehmann, R., & Fuller, M. T. (2002). A germline-specific gap junction protein required for survival of differentiating early germ cells. Development, 129(10), 2529–2539. https://doi.org/10.1242/dev.129.10.2529
Guichet, A., Wucherpfennig, T., Dudu, V., Etter, S., Wilsch‐Bräuniger, M., Hellwig, A., González‐Gaitán, M., Huttner, W. B., & Schmidt, A. A. (2002). Essential role of endophilin A in synaptic vesicle budding at the Drosophila neuromuscular junction. The EMBO Journal, 21(7), 1661–1672. https://doi.org/10.1093/emboj/21.7.1661
Ozon, S., Guichet, A., Gavet, O., Roth, S., & Sobel, A. (2002). Drosophila Stathmin: A Microtubule-destabilizing Factor Involved in Nervous System Formation. Molecular Biology of the Cell, 13(2), 698–710. https://doi.org/10.1091/mbc.01-07-0362
Guichet, A., Peri, F., & Roth, S. (2001). Stable Anterior Anchoring of the Oocyte Nucleus Is Required to Establish Dorsoventral Polarity of the Drosophila Egg. Developmental Biology, 237(1), 93–106. https://doi.org/10.1006/dbio.2001.0354
Jiménez, G., Guichet, A., Ephrussi, A., & Casanova, J. (2000). Relief of gene repression by torso RTK signaling: role of capicua in Drosophila terminal and dorsoventral patterning. Genes & Development, 14(2), 224–231.
Tomancak, P., Guichet, A., Zavorszky, P., & Ephrussi, A. (1998). Oocyte polarity depends on regulation of gurken by Vasa. Development, 125(9), 1723–1732. https://doi.org/10.1242/dev.125.9.1723
Florence, B., Guichet, A., Ephrussi, A., & Laughon, A. (1997). Ftz-F1 is a cofactor in Ftz activation of the Drosophila engrailed gene. Development, 124(4), 839–847. https://doi.org/10.1242/dev.124.4.839
Guichet, A., Copeland, J. W. R., Erdélyi, M., Hlousek, D., Závorszky, P., Ho, J., Brown, S., Percival-Smith, A., Krause, H. M., & Ephrussi, A. (1997). The nuclear receptor homologue Ftz-F1 and the homeodomain protein Ftz are mutually dependent cofactors. Nature, 385(6616), 548–552. https://doi.org/10.1038/385548a0
Erdélyi, M., Michon, A.-M., Guichet, A., Glotzer, J. B., & Ephrussi, A. (1995). Requirement for Drosophila cytoplasmic tropomyosin in oskar mRNA localization. Nature, 377(6549), 524–527. https://doi.org/10.1038/377524a0
Overexpression of Partner of Numb Induces Asymmetric Distribution of the PI4P 5-Kinase Skittles in Mitotic Sensory Organ Precursor Cells in Drosophila | PLOS ONE. (n.d.). Retrieved February 19, 2024, from https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003072
Overexpression of Partner of Numb Induces Asymmetric Distribution of the PI4P 5-Kinase Skittles in Mitotic Sensory Organ Precursor Cells in Drosophila | PLOS ONE. (n.d.). Retrieved February 19, 2024, from https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003072

Theses

  • Maëlys Loh (2022) : Molecular asymmetries controlling nuclear positioning in the oocyte of Drosophila melanogaster
  • Julie Jouette (2017) : Cross-relationship between nuclear positioning and microtubule organisation in oocyte polarisation in Drosophila: an ex-vivo light microscopy and photomanipulation approach
  • Pierre-Marie Le Droguen (2013) : Role of the microtubule network in the morphogenesis of the tracheal system in the Drosophila embryo
  • Alexandre Baffet (2010) : Microtubule organisation and cell polarity in Drosophila
  • Julien Compagnon (2008) : Drosophila vesicle trafficking during ovogenesis
  • Louis Gervais (2006): Study of the relationship between microtubule dynamics and polarised transport in the Drosophila oocyte.
  • Jens Januschke (2005): mRNA localization in the Drosophila oocyte

Collaborations

GRANTS – FUNDING

Nuclear Deformation in Eukaryotes, Projet Emergence en Recherche, IDEX Université Paris Cité (coordinateurs Fred Bernard et Sylvain Brun).