TEAM

Physical approaches to cell dynamics and tissue morphogenesis

Group leader : P.F. Lenne

Understanding the physical origin of cell and tissue shapes

FOR BEGINNERS

We aim to identify the physical principles controlling the generation of tissue shapes (morphogenesis), in particular how mechanical forces sculpt tissues during embryonic development. To do so, we develop and apply quantitative approaches to observe, perturb and predict morphogenesis. We study how cell collectives generate and respond to mechanical forces, differentiate and self-organize, by probing different scales, from the molecular organization of cell-cell contacts to the global shape of tissues.

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FOR SPECIALISTS
1. Mechanics of cell contacts and tissue morphogenesis

The shaping of tissues and organs relies on the ability of cells to adhere together and to deform in a coordinated manner. It is therefore key to understand how cell-generated forces produce cell shape changes, and how such forces transmit through a group of adhesive cells to generate tissue flows at the embryo scale. In this context, we develop and apply approaches to probe local and global mechanics. For example, we use optical manipulation to measure the forces acting at cell contacts and their material properties. We identify the time-dependent viscoelastic properties of cell contacts and how they impinge on tissue morphogenesis.

2. Axis formation and polarization

How do animals and tissues acquire specific axes (e.g. anteroposterior or dorsoventral) during morphogenesis?  Addressing this question is crucial to understand the formation of the body plan in animals and the organization of cell collections into functional organs.

In the group, we focus on how multicellular systems generate axes and how cells polarize in the embryo.

Axis formation in embryonic organoids

How mechanical constraints guide embryonic patterning and axis formation has been little studied, especially in mammalian development. We address this question using 3D aggregates of mouse embryonic stem cells that self-organize into embryonic organoids called Gastruloids. Gastruloids undergo robust and reproducible symmetry breaking, axial organization, gastrulation-like movement and gene expression patterns mirroring events in the embryo.Our working model is that gene expression at the cellular scale modulates the biomechanics of cell contacts, which triggers morphogenetic movements and mechanical stresses. In turn, they modulate and orient patterns of gene expression within the tissues. To test this hypothesis, we develop a systematic approach, in which single- and multi-cellular dynamics can be interrogated, using live imaging of Gastruloids over days to generate quantitative maps of tissue flows and tissue mechanical stresses. We control mechanochemical conditions, to see how they affect single cell and collective cell behaviour during the self-organization process.

brachuryevolution kineticmaps

Cell polarization in tissues

We dissect the mechanisms of cell polarity establishment using the  C. elegans embryo as a model system. We focus on the coupling between biochemical signaling and cell/tissue mechanics. In particular, we determine how neuronal precursors locally integrate Wnt signalling by visualizing ligand/receptor interactions both in vivo and in vitro.

emb3_stack

3. Technological developments

Our group develops optical-based approaches to study cell dynamics and tissue morphogenesis, including laser manipulation, laser nanodissection, fluorescence fluctuations spectroscopy and light-sheet microscopy.


Selected publications

PUBLICATION

Wnt ligands regulate the asymmetric divisions of neuronal progenitors in C. elegans embryos

Shilpa Kaur, Pauline Mélénec, Sabrina Murgan, Guillaume Bordet, Pierre Recouvreux, Pierre-François Lenne, Vincent Bertrand
Development 2020 147: dev183186 doi: 10.1242/dev.183186 Published 6 April 2020 PMID: 32156756

PUBLICATION

Tissue 'melting' sculpts embryo

Pierre-François Lenne, Vikas Trivedi
Nature . 2018 Sep;561(7723):315-316. doi: 10.1038/d41586-018-06108-7. PMID: 30224727

PUBLICATION

Polarization-resolved microscopy reveals a muscle myosin motor-independent mechanism of molecular actin ordering during sarcomere maturation.

Loison, Weitkunat M, Kaya-Çopur A, Nascimento Alves C, Matzat T, Spletter ML, Luschnig S, Brasselet S, Lenne PF, Schnorrer F.
PLoS Biol. 2018 Apr 27;16(4):e2004718. doi: 10.1371/journal.pbio.2004718. PMID: 29702642

PUBLICATION

Viscoelastic Dissipation Stabilizes Cell Shape Changes during Tissue Morphogenesis

Raphaël Clément, Benoît Dehapiot, Claudio Collinet, Thomas Lecuit, Pierre-François Lenne
Current Biology

PUBLICATION

Patterned cortical tension mediated by N-cadherin controls cell geometric order in the Drosophila eye.

Chan EH, Chavadimane Shivakumar P, Clément R, Laugier E, Lenne PF.
Elife. 2017 May 24;6. pii: e22796. PMID: 28537220

PUBLICATION

Direct laser manipulation reveals the mechanics of cell contacts in vivo.

Bambardekar K, Clément R, Blanc O, Chardès C, Lenne PF.
Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1416-21. PMID: 25605934

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

Bond flexibility and low valence promote finite clusters of self-aggregating particles.

Markova O, Alberts J, Munro E, Lenne PF.
Phys Rev Lett. 2012 Aug 17;109(7):078101. PMID: 23006403

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

Experimental validation of force inference in epithelia from cell to tissue scale

Weiyuan Kong, Olivier Loison, Pruthvi Chavadimane Shivakumar, Eunice HoYee Chan, Mehdi Saadaoui, Claudio Collinet, Pierre-François Lenne, Raphaël Clément
Sci Rep . 2019 Oct 10;9(1):14647. doi: 10.1038/s41598-019-50690-3. PMID: 31601854

PUBLICATION

Distinct contributions of tensile and shear stress on E-cadherin levels during morphogenesis

Girish R Kale, Xingbo Yang, Jean-Marc Philippe, Madhav Mani, Pierre-François Lenne, Thomas Lecuit
Nat Commun . 2018 Nov 27;9(1):5021. doi: 10.1038/s41467-018-07448-8. PMID: 30479400

PUBLICATION

Laser Ablation to Probe the Epithelial Mechanics in Drosophila.

Shivakumar PC, Lenne PF.
Methods Mol Biol. 2016;1478:241-251. PMID: 27730586

PUBLICATION

Molecular clustering in the cell: from weak interactions to optimized functional architectures.

Recouvreux P, Lenne PF.
Curr Opin Cell Biol. 2016 Feb;38:18-23. PMID: 26829487

PUBLICATION

Measuring forces and stresses in situ in living tissues.

Sugimura K, Lenne PF, Graner F.
Development. 2016 Jan 15;143(2):186-96. PMID: 26786209

PUBLICATION

Calcium Spikes in Epithelium: study on Drosophila early embryos.

Markova O, Sénatore S, Chardès C, Lenne PF.
Sci Rep. 2015 Jul 22;5:11379. PMID: 26198871

PUBLICATION

Superresolution measurements in vivo: imaging Drosophila embryo by photoactivated localization microscopy.

Truong Quang BA, Lenne PF.
Methods Cell Biol. 2015;125:119-42. PMID: 25640427

PUBLICATION

Probing cell mechanics with subcellular laser dissection of actomyosin networks in the early developing Drosophila embryo.

Rauzi M, Lenne PF.
Methods Mol Biol. 2015;1189:209-18. PMID: 25245696

PUBLICATION

Clustering of low-valence particles: structure and kinetics.

Markova O, Alberts J, Munro E, Lenne PF.
Phys Rev E Stat Nonlin Soft Matter Phys. 2014 Aug;90(2):022301. PMID: 25215732

PUBLICATION

Setting-up a simple light sheet microscope for in toto imaging of C. elegans development.

Chardes C., Melenec P., Bertrand V. And Lenne P.F.
J Vis Exp. 2014 May 5;(87). PMID: 24836407

PUBLICATION

Membrane microdomains: from seeing to understanding.

Truong-Quang BA, Lenne PF.
Front Plant Sci. 2014 Feb 18;5:18. PMID: 24600455

PUBLICATION

Cortical forces in cell shape changes and tissue morphogenesis.

Rauzi M, Lenne PF.
Curr Top Dev Biol. 2011;95:93-144 PMID: 21501750

PUBLICATION

Calcium signaling in developing embryos: focus on the regulation of cell shape changes and collective movements.

Markova O, Lenne PF.
Semin Cell Dev Biol. 2012 May;23(3):298-307. PMID: 22414534

PUBLICATION

FCS diffusion laws in two-phase lipid membranes: determination of domain mean size by experiments and Monte Carlo simulations.

Favard C, Wenger J, Lenne PF, Rigneault H.
Biophys J. 2011 Mar 2;100(5):1242-51. PMID: 21354397

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

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

Probing cell-surface dynamics and mechanics at different scales.

Lenne PF.
Histochem Cell Biol. 2009 Sep;132(3):247-52. PMID: 19633983

PUBLICATION

Fluorescence fluctuations analysis in nanoapertures: physical concepts and biological applications.

Lenne PF, Rigneault H, Marguet D, Wenger J.
Histochem Cell Biol. 2008 Nov;130(5):795-805. PMID: 18800223

PUBLICATION

Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation.

Lasserre R, Guo XJ, Conchonaud F, Hamon Y, Hawchar O, Bernard AM, Soudja SM, Lenne PF, Rigneault H, Olive D, Bismuth G, Nunès JA, Payrastre B, Marguet D, He HT.
Nat Chem Biol. 2008 Sep;4(9):538-47. PMID: 18641634

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

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

Dynamic molecular confinement in the plasma membrane by microdomains and the cytoskeleton meshwork.

Lenne PF, Wawrezinieck L, Conchonaud F, Wurtz O, Boned A, Guo XJ, Rigneault H, He HT, Marguet D.
EMBO J. 2006 Jul 26;25(14):3245-56. PMID:16858413

PUBLICATION

Fluorescence correlation spectroscopy diffusion laws to probe the submicron cell membrane organization

Laure Wawrezinieck, Hervé Rigneault, Didier Marguet, Pierre-François Lenne
Biophys J . 2005 Dec;89(6):4029-42. doi: 10.1529/biophysj.105.067959. Epub 2005 Sep 30. PMID: 16199500

PUBLICATION

Enhancement of single-molecule fluorescence detection in subwavelength apertures.

Rigneault H, Capoulade J, Dintinger J, Wenger J, Bonod N, Popov E, Ebbesen TW, Lenne PF.
Phys Rev Lett. 2005 Sep 9;95(11):117401. PMID:16197045

Lab Twitter


Funding

ANR

FRM

CENTURI

Members more

valentin Dunsing victoria Dupuis   simon Gsell   Claire Chardes Raphael Clement Kenji Nishizawa Pierre Recouvreux Sham Tlili
Pierre-françois Lenne
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Pierre-françois Lenne

Researcher

Pierre-François studied physics at the University of Paris and Ecole Normale Supérieure of Paris, France, before completing his PhD in soft matter physics at the University of Grenoble, France. After postdoctoral research in the cell biology and biophysics unit of EMBL (Heidelberg, Germany), he joined the National Centre for Scientific Research (CNRS) as a Chargé de Recherche (research scientist) in the Fresnel Institute of Marseille. Group leader at the Institute for Developmental Biology of Marseilles-Luminy (IBDM) and CNRS research director since 2009, his current research focuses on cell dynamics and mechanics in the context of tissue morphogenesis.

valentin Dunsing
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valentin Dunsing

Researcher

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  • 7ème - TPR2
victoria Dupuis
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victoria Dupuis

Technical staff

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alice Gros

PhD student

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  • 7ème - TPR2
simon Gsell
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simon Gsell

Postdoctoral fellow

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  • 7ème - TPR2
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Katia Barrett

PhD student

Claire Chardes
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Claire Chardes

Technical staff

Claire Chardès joined the team in 2009. Claire graduated in 2004 from the engineer school ENSPM (‘Ecole Nationale Supérieure de Physique de Marseille). Her project focuses on light sheet microscopy (SPIM and DSLM). She also participates in other projects in optics, image processing and image analysis.

Raphael Clement
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Raphael Clement

Researcher

Raphaël is interested in the physical aspects of shape generation during embryonic developement. He joined the team in 2015 as a research scientist (Chargé de Recherche CNRS), after completing his PhD in Paris (Matière et Systèmes Complexes, Paris Diderot) and a postdoctoral fellowship in Nice (J.A. Dieudonné, Nice Sophia-Antipolis).

Kenji Nishizawa
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Kenji Nishizawa

Postdoctoral fellow

Pierre Recouvreux
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Pierre Recouvreux

University lecturer

Pierre joined the lab in September 2013 as a University lecturer. He studied physics at the Ecole Normale Supérieure de Lyon (France) before focusing his research on the physics of biological systems. Pierre completed his PhD at the Institut Curie (Paris, France) working on the mechanical properties of single chromatin fibers using magnetic tweezers (under the supervision of J-L. Viovy). In 2010, he joined the group of Marileen Dogterom (AMOLF Insitute, Amsterdam) as a postdoctoral researcher. He worked on the microtubule-based establishment of polarization in fission yeast cells. In the group Pierre is now working on the physical aspects of neurulation in Caenorhabditis elegans embryos, in collaboration with the group of Vincent Bertrand at the IBDM.

Sham Tlili
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Sham Tlili

Researcher

Alumni

Overview

Model organism
Biological process studied
  • Axis formation
  • Gastrulation
Technical approaches
  • Molecular biology
  • Experimental embryology
Medical applications
  • Tissue engineering