Team 09: Epithelial Growth and Morphogenesis

The living world has an infinite variety of shapes and sizes at the scale of whole organisms and this diversity contributes to our wonder for nature. Nevertheless, the existence of this diversity is not based on aesthetic criteria but on functional constraints. This is the case with the neck of the giraffe, reaching the highest leaves, or the fins of the flying fish mimicking the wing of the birds. The same diversity of forms, based on the same functional constraints, exists also at the level of our organs. For example, the tree structure of our lungs maximizes the exchange surface between air and blood to facilitate gas exchange. It is therefore important to understand how our genes carve these organs into a specific form (morphogenesis) and with an appropriate size (growth). The study of mechanisms controlling growth and morphogenesis is based on dynamic multi-scale biological processes (molecular, cellular and tissular) and requires approaches involving developmental biology, genetics, cell biology and biophysics.

In addition to these basic aspects, our work is also medically relevant since 80% of cancers have an epithelial origin and deregulation of the mechanisms controlling their growth or their morphogenesis are involved in tumor development. In fact, many of the genes we are studying are tumor suppressors or oncogenes in humans. In addition, some of these genes are also involved in dystrophies in humans - including the gene encoding dystrophin, involved in Duchenne and Becker dystrophies - and their study in our system sheds a new light on their involvement in these genetic diseases.

 

Research

 The mechanisms controlling growth and morphogenesis are easier to study in epithelium because the epithelial cells have a relatively simple and very stereotyped form. Thus any defect in shape or size is easily observable and computable. In addition, the majority of our organs are made up of this cell type, characterized by closely juxtaposed cells, polarized, associated by intercellular junctions and resting on a basal lamina. We chose Drosophila (fruit fly) as a model organism, for the unequaled possibilities it offers in terms of genetic tools and cellular imaging. Specifically, we use follicular cells of the Drosophila ovaries as an in vivo epithelium model. The ovarian follicular epithelium has a morphology very similar to mammalian epithelia and a rapid but strictly controlled growth. Anatomically, this epithelium surrounds the germ cells within the reproductive organ, forming 'ovarian follicles' or 'egg chambers', precursors of the future egg. Interestingly, the elongation of the ovarian follicle, which progressively matures from a spherical to an elongated form, is generated by the follicular epithelium. 

Thus, the projects developed within the team focus on two axes:

1. Understand the growth coordination mechanisms between two adjacent tissues. For this, we analyze the modes of communication between the germ cells and the follicular cells, allowing the synchronization of their growth during the development of the ovarian follicles and thus ensuring the homeostasis of the reproductive organ

2. Understand the morphogenetic mechanisms leading to the elongation of ovarian follicles. We study on the one hand the involvement of the JAK-STAT pathway and the apical domain of follicular epithelial cells, in contact with the germ cells during the early elongation of the follicles. On the other hand, we analyze the involvement of the Dystrophin-Dystroglycan protein complex and the basal domain of the epithelium in the later follicle elongation phase and especially its implication in planar cell polarity and extracellular matrix organization. 

Research thematics

People

Last Name First Name Position Contact
Chloe ABREU profile picture ABREU Chloe -
Olivier BARDOT profile picture BARDOT Olivier Associate Professor
Lisa CALVARY profile picture CALVARY Lisa Ph.D Student
Cynthia DENNIS profile picture DENNIS Cynthia Post-doctoral Fellow
Corinne LOURS-CALET profile picture LOURS-CALET Corinne Associate Professor
Vincent MIROUSE profile picture MIROUSE Vincent Principal Investigator
Graziella RICHARD profile picture RICHARD Graziella Assistant Engineer
Brianne SIMON profile picture SIMON Brianne -
Caroline VACHIAS profile picture VACHIAS Caroline Research Engineer

Publications

  • 2020
  • 2018
    • S. Elis, A. Desmarchais, E. Cardona, S. Fouchecourt, R. Dalbies-Tran, T. Nguyen, V. Thermes, V. Maillard, P. Papillier, S. Uzbekova, J. Bobe, J. Couderc and P. Monget, “Genes Involved in Drosophila melanogaster Ovarian Function Are Highly Conserved Throughout Evolution.”, Genome Biol Evol, vol. 10 (10) , pp. 2629–2642, 2018.
    • H. Alegot, P. Pouchin, O. Bardot and V. Mirouse, “Jak-Stat pathway induces Drosophila follicle elongation by a gradient of apical contractility.”, eLife, vol. 7 , 2018.
  • 2017
    • J. Couderc, G. Richard, C. Vachias and V. Mirouse, “Drosophila LKB1 is required for the assembly of the polarized actin structure that allows spermatid individualization.”, PLoS ONE, vol. 12 (8) , pp. e0182279, 2017.
  • 2015
    • I. Brigaud, J. Duteyrat, J. Chlasta, S. Le Bail, J. Couderc and M. Grammont, “Transforming Growth Factor beta/activin signalling induces epithelial cell flattening during Drosophila oogenesis.”, Biology open, vol. 4 (3) , pp. 345–54, 2015.
  • 2014
    • C. Vachias, C. Fritsch, P. Pouchin, O. Bardot and V. Mirouse, “Tight coordination of growth and differentiation between germline and soma provides robustness for drosophila egg development.”, Cell Rep, vol. 9 (2) , pp. 531–41, 2014.
    • C. Lours-Calet, L. Alvares, A. El-Hanfy, S. Gandesha, E. Walters, D. Sobreira, K. Wotton, E. Jorge, J. Lawson, A. Kelsey Lewis, M. Tada, C. Sharpe, G. Kardon and S. Dietrich, “Evolutionarily conserved morphogenetic movements at the vertebrate head-trunk interface coordinate the transport and assembly of hypopharyngeal structures.”, Dev. Biol. (NY), vol. 390 (2) , pp. 231–46, 2014.
    • G. Borrel, N. Parisot, H. Harris, E. Peyretaillade, N. Gaci, W. Tottey, O. Bardot, K. Raymann, S. Gribaldo, P. Peyret, P. O'Toole and J. Brugere, “Comparative genomics highlights the unique biology of Methanomassiliicoccales, a Thermoplasmatales-related seventh order of methanogenic archaea that encodes pyrrolysine.”, BMC genomics, vol. 15 , pp. 679, 2014.
  • 2013
    • B. Aigouy and V. Mirouse, “ScientiFig: a tool to build publication-ready scientific figures.”, Nat. Methods, vol. 10 (11) , pp. 1048, 2013.
    • A. Baanannou, L. Mojica-Vazquez, G. Darras, JL. Couderc, D. Cribbs, M. Boube and H. Bourbon, “Drosophila distal-less and Rotund bind a single enhancer ensuring reliable and robust bric-a-brac2 expression in distinct limb morphogenetic fields.”, PLoS Genet., vol. 9 (6) , pp. e1003581, 2013.
    • P. Bardet, B. Guirao, C. Paoletti, F. Serman, V. Leopold, F. Bosveld, Y. Goya, V. Mirouse, F. Graner and Y. Bellaiche, “PTEN controls junction lengthening and stability during cell rearrangement in epithelial tissue.”, Dev. Cell, vol. 25 (5) , pp. 534–46, 2013.
    • G. Borrel, H. Harris, N. Parisot, N. Gaci, W. Tottey, A. Mihajlovski, J. Deane, S. Gribaldo, O. Bardot, E. Peyretaillade, P. Peyret, P. O'Toole and J. Brugere, “Genome Sequence of "Candidatus Methanomassiliicoccus intestinalis" Issoire-Mx1, a Third Thermoplasmatales-Related Methanogenic Archaeon from Human Feces.”, Genome announcements, vol. 1 (4) , 2013.
  • 2012
    • C. Penalva and V. Mirouse, “Tissue-specific function of Patj in regulating the Crumbs complex and epithelial polarity.”, Development, vol. 139 (24) , pp. 4549–54, 2012.
    • Y. Renaud, A. Baillif, J. Perez, M. Agier, E. Mephu Nguifo and V. Mirouse, “DroPNet: a web portal for integrated analysis of Drosophila protein-protein interaction networks.”, Nucleic Acids Res., vol. 40 (Web Server issue) , pp. W134–9, 2012.
  • 2010
    • V. Mirouse and M. Billaud, “The LKB1/AMPK polarity pathway.”, FEBS Lett., vol. 585 (7) , pp. 981–5, 2010.
    • C. Vachias, JL. Couderc and M. Grammont, “A two-step Notch-dependant mechanism controls the selection of the polar cell pair in Drosophila oogenesis.”, Development, vol. 137 (16) , pp. 2703–11, 2010.
    • H. Doerflinger, N. Vogt, I. Torres, V. Mirouse, I. Koch, C. Nusslein-Volhard and D. St Johnston, “Bazooka is required for polarisation of the Drosophila anterior-posterior axis.”, Development, vol. 137 (10) , pp. 1765–73, 2010.
    • E. Morais-de-Sa, V. Mirouse and D. St Johnston, “aPKC phosphorylation of Bazooka defines the apical/lateral border in Drosophila epithelial cells.”, Cell, vol. 141 (3) , pp. 509–23, 2010.
  • 2009
    • V. Mirouse, C. Christoforou, C. Fritsch, D. St Johnston and R. Ray, “Dystroglycan and perlecan provide a basal cue required for epithelial polarity during energetic stress.”, Dev. Cell, vol. 16 (1) , pp. 83–92, 2009.
  • 2008
    • L. Alvares, C. Lours, A. El-Hanfy and S. Dietrich, “Microsurgical manipulation of the notochord.”, Meth. Mol. Biol., vol. 461 , pp. 289–303, 2008.