TEAM

Tissue Architecture and Plasticity

Group leader : T. Lecuit

We study how epithelial tissues maintain a robust organisation and extensively remodel as they grow and change their shape during development.

FOR BEGINNERS

Epithelia form mechanical and chemical barriers that are both structurally robust and constantly remodelled during embryogenesis and organogenesis from nematodes to humans. Perturbations in this balance underlie solid cancer progression. How this is controlled is a fundamental unanswered question in biology. Our major ambition is to understand this problem using interdisciplinary approaches that combine the most quantitative analyses with physiological studies in whole organisms.  We decipher the biochemical underpinnings of cell and tissue mechanics, namely how forces are generated and how they produce deformations, and characterize their regulation by conserved signalling pathways. Our group requires the complementary expertise of cell and developmental biologists, physicists and engineers etc.

One of the most remarkable properties of living tissues is that they combine robustness in their organisation, and extensive plasticity in their dynamics. This is especially true in epithelial sheets, where cells are usually (but not always) arranged in monolayers. Through the tight association between cells mediated by adhesion molecules, in particular E-cadherin, cells are cohesive and allow the formation of epithelial barriers that separate different physiological environments and protect the organism against pathogens. Epithelia also extensively remodel during development, and in the adult. For instance, epithelia grow and produce new cells via cell division. Cells remodel their contacts and move with respect to each other and contribute to the remodelling of the tissue.

Through these remodelling events, tissues acquire complex shapes and maintain their final organization as new cells replace dead cells.

Tissue robustness requires adhesion mediated by E-cadherin complexes. Plasticity is an active process driven by actomyosin contractility whereby cells remodel their contacts. These forces are transmitted at the cell contacts by E-cadherin complexes.

We address the following major questions:

  • how forces emerge from interactions between motors, actin filaments and crosslinker.
  • How E-cadherin complexes control adhesion and force transmission.
  • How intercellular developmental signals control cell mechanics to drive tissue extension and invagination.
  • How cell division and tissue growth affect tissue mechanics and vice versa.

We use the fruitfly Drosophila to address these problems. The major components of cell mechanics and their regulation are shared with humans and this organism lends itself to a very powerful combination of functional, molecular and physical approaches. Our group is largely interdisciplinary and employs a large battery of experimental methods ranging from biochemistry, to genetics, quantitative imaging and modelling.

FOR SPECIALITS

The morphogenesis of animals has fascinated scientists for decades. Embryologists, geneticists, cell biologists and now physicists have considerably advanced our understanding of how multicellular organisms are formed. There are 3 major trends in the study of morphogenesis. A longstanding interest for the spatial control of cell identity/behaviour led to the identification of general principles of how information flow organizes morphogenesis. The cell biological foundation of morphogenesis emerged gradually and exploded 10 years ago with the advent of live imaging. The cell shape changes that underlie tissue invagination and extension were characterized: apical constriction, cell intercalation. Cell morphogenesis requires force generation and its spatial control by specific biochemical pathway. A more recent trend, fostered by a quantitative description of cell dynamics allows a quantitative/physical understanding of morphogenesis.  The field of tissue morphogenesis is thus a broadly expanding and active, interdisciplinary research area.

Research in Drosophila is at the forefront of our understanding of how biochemical pathways control cell mechanics and cell shape changes driving epithelial morphogenesis. Tissue elongation and invagination are two universal classes of tissue shape changes that drive gastrulation. Invagination of the mesoderm, on the ventral half of the embryo, has served as a paradigm for epithelial invagination driven by apical cell constriction. Similar processes drive neural tube closure in vertebrates, and invagination of the endoderm in nematodes, ascidians etc. Apical constriction requires apical Myosin-II (MyoII) phosphorylation by the kinase ROCK, which itself is activated by the small GTPase Rho1 and upstream GEF, such as RhoGEF2. Extension of the ventral lateral ectoderm called the germband, or germband extension (GBE), has become a paradigm for the study of epithelial extension. This process is driven by spatially ordered neighbour exchanges, or cell intercalation. During intercalation cell junctions are remodelled in a planar polarized manner. This is driven by the polarized enrichment of Myosin-II cables in ‘shrinking’, so called ‘vertical’ junctions (Fig. 1A), and the corresponding reduction in Ecad levels. As in apical constriction, MyoII polarized recruitment is dependent on upstream activation by ROCK, and RhoGEFs such as RhoGEF2(15). Thus, similar biochemical pathways underlie force generation in different morphogenetic processes. Recent studies points to deeper similarities. In apical constriction and cell intercalation, actomyosin networks alternate phases of deformation and stabilization. Cell deformation is driven by actomyosin concentration in medial apical contractile pulses (Fig. 1B). The frequency of pulses may define the speed of deformations. While stabilization is apical in mesoderm cells, it only occurs at shrinking ‘vertical’ junctions in the intercalating ectodermal cells (Fig. 1B, C). This ratchet mechanism emerged as a general feature of epithelial mechanics. Although mesoderm and ectodermal cells display similar pulsatile apical actomyosin contractility, their behaviour is different. In ectoderm cells, actomyosin pulses flow anisotropically, ie. in a planar polarized manner towards shrinking junctions (Fig. 1B). However, in mesoderm cells, pulses do not flow and drive an isotropic deformation (Fig. 1C). The presence or absence of flow is thus a point of developmental bifurcation between constriction (tissue invagination), and intercalation (tissue extension).

These findings lead to a general framework of morphogenesis based on i) spatial control over cell deformation by actomyosin flows and stabilization, and ii) temporal control by contractile pulses.

Open questions : A number of key general questions remain unanswered.

  • How is pulsatile contractility by actomyosin networks controlled?
  • What underlies the different mechanical properties of stabilizing and deforming actomyosin networks?
  • What controls the presence/absence of actomyosin flows and how is the flow oriented?
  • How are actomyosin forces transmitted at the cell-cell contacts? Is force transmission by adhesive clusters regulated by actomyosin tension? Does force transmission feedback on force generation?
  • What pathways are responsible for the spatial control over cell deformations and cell stabilization? What underlies planar polarization in intercalation? How do cells communicate during this process?
  • How are local mechanical properties coordinated between cells to achieve robust tissue deformation?

Main publications

PUBLICATION

Oscillation and polarity of E-cadherin asymmetries control actomyosin flow patterns during morphogenesis.

Levayer R, Lecuit T.
Dev Cell. 2013 Jul 29;26(2):162-75. PMID: 23871590

PUBLICATION

Adhesion disengagement uncouples intrinsic and extrinsic forces to drive cytokinesis in epithelial tissues.

Guillot C, Lecuit T.
Dev Cell. 2013 Feb 11;24(3):227-41. PMID: 23410938

PUBLICATION

Spatial regulation of Dia and Myosin-II by RhoGEF2 controls initiation of E-cadherin endocytosis during epithelial morphogenesis.

Levayer R, Pelissier-Monier A, Lecuit T.
Nat Cell Biol. 2011 May;13(5):529-40. PMID: 21516109

PUBLICATION

Planar polarized actomyosin contractile flows control epithelial junction remodelling.

Rauzi M, Lenne PF, Lecuit T.
Nature. 2010 Dec 23;468(7327):1110-4. PMID: 21068726

PUBLICATION

Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis.

Rauzi M, Verant P, Lecuit T, Lenne PF.
Nat Cell Biol. 2008 Dec;10(12):1401-10. PMID: 18978783

PUBLICATION

A two-tiered mechanism for stabilization and immobilization of E-cadherin.

Cavey M, Rauzi M, Lenne PF, Lecuit T.
Nature. 2008 Jun 5;453(7196):751-6. PMID: 18480755

PUBLICATION

Spatial control of actin organization at adherens junctions by a synaptotagmin-like protein Btsz.

Pilot F, Philippe JM, Lemmers C, Lecuit T.
Nature. 2006 Aug 3;442(7102):580-4. PMID: 16862128

PUBLICATION

Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation.

Bertet C, Sulak L, Lecuit T.
Nature. 2004 Jun 10;429(6992):667-71. PMID: 15190355

PUBLICATION

Trafficking through Rab11 endosomes is required for cellularization during Drosophila embryogenesis.

Pelissier A, Chauvin JP, Lecuit T.
Curr Biol. 2003 Oct 28;13(21):1848-57. PMID: 14588240
Other publications

PUBLICATION

Principles of E-Cadherin Supramolecular Organization In Vivo.

Truong Quang BA, Mani M, Markova O, Lecuit T, Lenne PF.
Curr Biol. 2013 Oct 29. pii: S0960-9822(13)01131-7. PMID:24184100

PUBLICATION

A global pattern of mechanical stress polarizes cell divisions and cell shape in the growing Drosophila wing disc.

Legoff L, Rouault H, Lecuit T.
Development. 2013 Oct;140(19):4051-9. PMID: 24046320

PUBLICATION

Mechanics of epithelial tissue homeostasis and morphogenesis.

Guillot C, Lecuit T.
Science. 2013 Jun 7;340(6137):1185-9. PMID: 23744939

PUBLICATION

Transcriptional and epigenetic signatures of zygotic genome activation during early drosophila embryogenesis.

Darbo E, Herrmann C, Lecuit T, Thieffry D, van Helden J.
BMC Genomics. 2013 Apr 5;14:226. http://www.ncbi.nlm.nih.gov/pubmed/23560912

PUBLICATION

Stability and dynamics of cell-cell junctions.

Collinet C, Lecuit T.
Prog Mol Biol Transl Sci. 2013;116:25-47. PMID: 23481189

PUBLICATION

Biomechanical regulation of contractility: spatial control and dynamics.

Levayer R, Lecuit T.
Trends Cell Biol. 2012 Feb;22(2):61-81. PMID: 22119497

PUBLICATION

Nuclear mechanics in differentiation and development.

Hampoelz B, Lecuit T.
Curr Opin Cell Biol. 2011 Dec;23(6):668-75. PMID: 22079175

PUBLICATION

Cell-to-cell contact and extracellular matrix. Editorial overview.

Lecuit T, Sonnenberg A.
Curr Opin Cell Biol. 2011 Oct;23(5):505-7. PMID: 21937209

PUBLICATION

Microtubule-induced nuclear envelope fluctuations control chromatin dynamics in Drosophila embryos.

Hampoelz B, Azou-Gros Y, Fabre R, Markova O, Puech PH, Lecuit T.
Development. 2011 Aug;138(16):3377-86. PMID: 21752932

PUBLICATION

Developmental biology. Gradient scaling and growth.

Le Goff L, Lecuit T.
Science. 2011 Mar 4;331(6021):1141-2. PMID: 21385701

PUBLICATION

Force generation, transmission, and integration during cell and tissue morphogenesis.

Lecuit T, Lenne PF, Munro E.
Annu Rev Cell Dev Biol. 2011;27:157-84. PMID: 21740231

PUBLICATION

An interview with Thomas Lecuit.

Lecuit T.
Development. 2010 Aug 1;137(15):2453-4. PMID: 20627959

PUBLICATION

alpha-catenin mechanosensing for adherens junctions.

Lecuit T.
Nat Cell Biol. 2010 Jun;12(6):522-4. PMID: 20453846

PUBLICATION

Lighting up developmental mechanisms: how fluorescence imaging heralded a new era.

Mavrakis M, Pourquié O, Lecuit T.
Development. 2010 Feb;137(3):373-87. PMID: 20081186

PUBLICATION

Repression of Wasp by JAK/STAT signalling inhibits medial actomyosin network assembly and apical cell constriction in intercalating epithelial cells.

Bertet C, Rauzi M, Lecuit T.
Development. 2009 Dec;136(24):4199-212. PMID: 19934015

PUBLICATION

Molecular bases of cell-cell junctions stability and dynamics.

Cavey M, Lecuit T.
Cold Spring Harb Perspect Biol. 2009 Nov;1(5):a002998. PMID: 20066121

PUBLICATION

Planar polarity and short-range polarization in Drosophila embryos.

Bertet C, Lecuit T.
Semin Cell Dev Biol. 2009 Oct;20(8):1006-13. PMID: 19486946

PUBLICATION

Developmental biology. Phase transition in a cell.

Le Goff L, Lecuit T.
Science. 2009 Jun 26;324(5935):1654-5. PMID: 19556492

PUBLICATION

Closing in on mechanisms of tissue morphogenesis.

Rauzi M, Lecuit T.
Cell. 2009 Jun 26;137(7):1183-5. PMID: 19563750

PUBLICATION

Current topics in developmental biology. Preface.

Lecuit T.
Curr Top Dev Biol. 2009;89:xi-xiii. doi: 10.1016/S0070-2153(09)89012-1. PMID: 19737639

PUBLICATION

Breaking down EMT.

Levayer R, Lecuit T.
Nat Cell Biol. 2008 Jul;10(7):757-9. PMID: 18591967

PUBLICATION

"Developmental mechanics": cellular patterns controlled by adhesion, cortical tension and cell division.

Lecuit T.
HFSP J. 2008 Apr;2(2):72-8. doi: PMID: 19404474

PUBLICATION

Imaging cellular and molecular dynamics in live embryos using fluorescent proteins.

Cavey M, Lecuit T.
Methods Mol Biol. 2008;420:219-38 PMID: 18641950

PUBLICATION

Orchestrating size and shape during morphogenesis.

Lecuit T, Le Goff L.
Nature. 2007 Nov 8;450(7167):189-92. PMID: 17994084

PUBLICATION

Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis.

Lecuit T, Lenne PF.
Nat Rev Mol Cell Biol. 2007 Aug;8(8):633-44. PMID: 17643125

PUBLICATION

Developmental control of nuclear size and shape by Kugelkern and Kurzkern.

Brandt A, Papagiannouli F, Wagner N, Wilsch-Bräuninger M, Braun M, Furlong EE, Loserth S, Wenzl C, Pilot F, Vogt N, Lecuit T, Krohne G, Grosshans J.
Curr Biol. 2006 Mar 21;16(6):543-52. PMID: 16458513

PUBLICATION

Developmental control of nuclear morphogenesis and anchoring by charleston, identified in a functional genomic screen of Drosophila cellularisation.

Pilot F, Philippe JM, Lemmers C, Chauvin JP, Lecuit T.
Development. 2006 Feb;133(4):711-23. PMID: 16421189

PUBLICATION

Cell adhesion: sorting out cell mixing with echinoid?

Lecuit T.
Curr Biol. 2005 Jul 12;15(13):R505-7. PMID: 16005283

PUBLICATION

Compartmentalized morphogenesis in epithelia: from cell to tissue shape.

Pilot F, Lecuit T.
Dev Dyn. 2005 Mar;232(3):685-94. PMID: 15712202

PUBLICATION

Adhesion remodeling underlying tissue morphogenesis.

Lecuit T.
Trends Cell Biol. 2005 Jan;15(1):34-42. PMID: 15653076

PUBLICATION

The fly Olympics: faster, higher and stronger answers to developmental questions. Conference on the Molecular and Developmental Biology of Drosophila.

Bejsovec A, Lecuit T, Modolell J.
EMBO Rep. 2004 Nov;5(11):1037-40. PMID: 15486566

PUBLICATION

Junctions and vesicular trafficking during Drosophila cellularization.

Lecuit T.
J Cell Sci. 2004 Jul 15;117(Pt 16):3427-33. PMID: 15252125

PUBLICATION

Regulation of membrane dynamics in developing epithelia.

Lecuit T.
Curr Opin Genet Dev. 2003 Aug;13(4):351-7. PMID: 12888007

PUBLICATION

Developmental biology: Flowers' wings, fruitflies' petals.

Desplan C, Lecuit T.
Nature. 2003 Mar 13;422(6928):123-4. PMID: 12634762

PUBLICATION

Developmental control of cell morphogenesis: a focus on membrane growth.

Desplan C, Lecuit T.
Nat Cell Biol. 2003 Feb;5(2):103-8. PMID: 12563275

Members more

Yannick Azou Deb sankar Banerjee   Claudio Collinet Charlène Guillot François Iv Ankita Jha Girish r. Kale Stephen Kerridge Loïc Le Goff   Manos Mavrakis Akankshi Munjal Vanessa Paduano Jean-marc Philippe Sabine Quitard Madan Rao
Thomas Lecuit
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Thomas Lecuit

Researcher

Yannick Azou
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Yannick Azou

University lecturer

Deb sankar Banerjee
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Deb sankar Banerjee

PhD student

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Alexandre Chuyen

Trainee

Claudio Collinet
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Claudio Collinet

Researcher

Charlène Guillot
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Charlène Guillot

PhD student

François Iv
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François Iv

Technical staff

Ankita Jha
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Ankita Jha

PhD student

Girish r. Kale
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Girish r. Kale

PhD student

Stephen Kerridge
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Stephen Kerridge

Researcher

Loïc Le Goff
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Loïc Le Goff

Researcher

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Qiyan Mao

Postdoctoral fellow

Manos Mavrakis
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Manos Mavrakis

Researcher

Akankshi Munjal
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Akankshi Munjal

PhD student

Vanessa Paduano
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Vanessa Paduano

PhD student

Jean-marc Philippe
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Jean-marc Philippe

Technical staff

Sabine Quitard
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Sabine Quitard

Technical staff

Madan Rao
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Madan Rao

University lecturer

Overview

Model organisms
Biological process studied
  • Cell and tissue morphogenesis, polarity
Biological techniques
  • Genetics, RNAi screening
  • Biochemistry, in vitro reconstituted assays
  • Quantitative live imaging of protein and cell dynamics
  • Cell biology
  • Optogenetics
  • Nano-ablation of subcellular structures
  • Modeling (through collaborations)