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

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.

Illustration 1

Nuclear migration in the Drosophila oocyte

Membrane organisation in the Drosophila oocyte

Illustration 3

Collective migration of tracheal cells in the Drosophila embryo

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
Maëlys LOH PhD Student
Fanny ROLAND GOSSELIN PhD Student

Dynein-mediated transport and membrane trafficking control PAR3 polarised distribution.

Jouette J, Guichet A, Claret SB. Elife. 2019 Jan 23;8:e40212. doi: 10.7554/eLife.40212. PMID: 30672465 Free PMC article.

 

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. Nat Commun. 2017 Apr 27;8:15168. doi: 10.1038/ncomms15168. PMID: 28447612 Free PMC article.

 

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 Jan 15;142(2):363-74. doi: 10.1242/dev.113472. PMID: 25564624

 

PI(4,5)P2 produced by the PI4P5K SKTL controls apical size by tethering PAR-3 in Drosophila epithelial cells.

Claret S, Jouette J, Benoit B, Legent K, Guichet A.Curr Biol. 2014 May 19;24(10):1071-9. doi: 10.1016/j.cub.2014.03.056. Epub 2014 Apr 24.PMID: 24768049

 

A developmentally regulated two-step process generates a noncentrosomal microtubule network in Drosophila tracheal cells.

Brodu V, Baffet AD, Le Droguen PM, Casanova J, Guichet A. Dev Cell. 2010 May 18;18(5):790-801. doi: 10.1016/j.devcel.2010.03.015. PMID: 20493812

 

The centrosome-nucleus complex and microtubule organization in the Drosophila oocyte.

Januschke J, Gervais L, Gillet L, Keryer G, Bornens M, Guichet A.Development. 2006 Jan;133(1):129-39. doi: 10.1242/dev.02179. Epub 2005 Nov 30.PMID: 16319114

 

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 Dec;135(23):3829-38. doi: 10.1242/dev.029009. Epub 2008 Oct 23. PMID: 18948416

GFP-Tagged Protein Detection by Electron Microscopy Using a GBP-APEX Tool in Drosophila. Bernard F, Jouette J, Durieu C, Le Borgne R, Guichet A, Claret S. Frontiers in Cell and Developmental Biology. (2021)

 

Nuclear Migration in the Drosophila Oocyte. Loh M, Guichet A, Bernard F. Journal of Visualized Experiments. (2021)

 

Autoinhibition of Cnn binding to γ-TuRCs prevents ectopic microtubule nucleation and cell division defects. Tovey CA, Tsuji C, Egerton A, Bernard F, Guichet A, de la Roche M, Conduit PT. Journal of Cell Biology (2021)

 

Microtubules originate asymmetrically at the somatic golgi and are guided via Kinesin2 to maintain polarity within neurons. Mukherjee A, Brooks PS, Bernard F, Guichet A, Conduit PT.  Elife. (2020)

 

Dual control of Kinesin-1 recruitment to microtubules by Ensconsin in Drosophila neuroblasts and oocytes. Metivier M, Monroy B, Gallaud E, Caous R, Pascal A, Richard-Parpaillon L, Guichet A, Ori-McKenney K, Giet R. Development (2019)

 

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

 

Nucleus positioning within Drosophila egg chamber. Bernard F, Lepesant JA, Guichet A. Semin Cell Dev Biol. (2018)

 

“Phosphoinositides and Cell Polarity in the Drosophila Egg Chamber”. Jouette J, Claret S, Guichet A. Results Cell Differentiation. (2017)

 

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)

 

Reliance of Wolbachia on High Rates of Host Proteolysis Revealed by a Genome-Wide RNAi Screen of Drosophila Cells. White PM, Serbus LR, Debec A, Codina A, Bray W, Guichet A, Lokey RS, Sullivan W. Genetics. (2017)

 

Methods to establish a Drosophila cell line. Drosophila. Debec A, Megraw T, Guichet A (2015) : Methods and Protocols. (2015)

 

Visualizing microtubule networks during Drosophila oogenesis using fixed and live imaging. Legent K, Tissot N, Guichet A. Methods Mol Biol . (2015)

 

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)

 

Establishment and mitotic characterization of new Drosophila acentriolar cell lines from DSas-4 mutant. Lecland N, Debec A, Delmas A, Pereira S, Malmanche N, Bouissou A, Dupré C, Jourdan A, Raynaud-Messina B, Maiato H, Guichet A, Biology Open (2013)

 

Drosophila Tubulin Binding Cofactors B is required for microtubule network formation and for cell polarity. Baffet A, Benoit B, Januschke J, Audo J, Gourhand V, Roth S, Guichet A. Molecular Biology of the Cell. (2012).

 

Nucleoporin 98-96 function is required for transit amplification divisions in the germ line of Drosophila melanogaster. Parrott BB, Chiang Y, Hudson A, Sarkar A, Guichet A, Schulz C.PLoS One. (2011)

 

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)

 

Phosphatidylinositol 4,5-bisphosphate directs spermatid cell polarity and exocyst localization in Drosophila. Fabian L, Wei HC, Rollins J, Noguchi T, Blankenship JT, Bellamkonda K, Polevoy G, Gervais L, Guichet A, Fuller MT, Brill JA. Molecular Biology of the Cell. (2010)

 

Drosophila stathmins bind tubulin heterodimers with high and variable stoichiometries.

Lachkar S, Lebois M, Steinmetz MO, Guichet A, Lal N, Curmi PA, Sobel A, Ozon S. J Biol Chem. (2010)

 

Interplay between Rab5 and PtdIns(4,5)P2 controls early endocytosis in the Drosophila germline.

Compagnon J, Gervais L, Roman MS, Chamot S, Guichet A. Journal of Cell Science. (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. Nicolas E, Chenouard N, Olivo-Marin JC, Guichet A. Molecular Biology of the Cell. (2009)

 

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).

 

Overexpression of partner of numb induces asymmetric distribution of the PI4P 5-Kinase Skittles in mitotic sensory organ precursor cells in Drosophila. Perdigoto CN, Gervais L, Overstreet E, Fischer J, Guichet A, Schweisguth F. PLoS One (2008)

 

Rab6 and the secretory pathway affect oocyte polarity in Drosophila. Januschke J, Nicolas E, Compagnon J, Formstecher E, Goud B, Guichet A. Development (2007).

 

Mise en place de la polarité au sein de l’ovocyte de drosophile, Guichet A, Biofutur, (2007)

 

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, Bornens 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).

 

Essential role of endophilin A in synaptic vesicle budding at the Drosophila neuromuscular junction. Guichet A, Wucherpfennig T, Dudu V, Etter S, Wilsch-Brauniger M, Hellwig A, Gonzalez-Gaitan M, Huttner WB, Schmidt AA. EMBO J. (2002).

 

Drosophila Stathmin : A microtubule destabilizing factor involved in nervous system formation. Ozon, S., Guichet, A., Gavet, O., Roth, S., Sobel, A., Molecular Biology of the Cell. (2002).

 

A germline-specific gap junction protein required for survival of differentiating early germ cells.Tazuke SI, Schulz C, Gilboa L, Fogarty M, Mahowald AP, Guichet A, Ephrussi A, Wood CG, Lehmann R, Fuller MT. Development. (2002)

 

Stable anterior anchoring of the oocyte nucleus is required to establish dorsoventral polarity of the Drosophila egg. Guichet, A., Peri, F., Roth, S. Developmental Biology. (2001).

 

Oocyte polarity depends on regulation of gurken by vasa.Tomancak, P., Guichet, A , Závorszky, P., Ephrussi, A., Development (1998).

 

Relief of gene repression by Torso signaling: role of capicua in Drosophila terminal and dorsoventral patterning. Jiménez J, Guichet A, Ephrussi A, Casanova J. Genes and Development (2000).

 

The nuclear receptor homologue Ftz-F1 and the homeodomain protein Ftz are mutually dependent cofactors. Guichet, A., Copeland, J. W. R., Erdélyi, M., Hlousek, D., Závorszky, P., Ho, J., Brown, S., Percival-Smith, A., Krause, H. M. and Ephrussi, A., (1997). Nature. 385 ; 548-552.

 

Ftz-F1 is a cofactor in Ftz activation of the Drosophila engrailed gene. Florence, B., Guichet, A., Ephrussi, A. and Laughon, A.,. Development. (1997)

 

Requirement for Drosophila cytoplasmic tropomyosin in oskar mRNA localisation. Erdélyi, M., Michon, A., Guichet, A., Bogucka Glotzer, J. and Ephrussi, A.). Nature. (1995)

 

 

  • Julie Jouette (2017) : Phosphoinositides et contrôle de la polarité cellulaire : régulations croisées entre la PIP5K Skittles et les protéines de polarité PAR1 et PAR3.
  • Nicolas Tissot (2015) : Relation croisée entre le positionnement du noyau et l’organisation des microtubules dans la polarisation de l’ovocyte chez la drosophile : approche par microscopie optique ex-vivo et photomanipulation
  • Pierre-Marie Le Droguen (2013) : Rôle du réseau de microtubules lors de la morphogénèse du système trachéal dans l’embryon de drosophile
  • Alexandre Baffet (2010) : Organisation des microtubules et polarité cellulaire chez la Drosophile
  • Julien Compagnon (2008) : Etude du trafic vésiculaire au cours de l’ovogenèse chez la Drosophile
  • Louis Gervais (2006): Etude des relations entre la dynamique du réseau de microtubules et le transport polarisé dans l’ovocyte.
  • Jens Januschke (2005) : mRNA localization in the Drosophila oocyte

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