Physical approaches to cell dynamics and tissue morphogenesis
Group leader : P.F. Lenne
Understanding the physical origin of cell and tissue shapes
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.
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.
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.
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.
April 6th, 2020
Wnt ligands regulate the asymmetric divisions of neuronal progenitors in C. elegans embryos
September 10th, 2018
Tissue 'melting' sculpts embryo
April 27th, 2018
Polarization-resolved microscopy reveals a muscle myosin motor-independent mechanism of molecular actin ordering during sarcomere maturation.
October 5th, 2017
Viscoelastic Dissipation Stabilizes Cell Shape Changes during Tissue Morphogenesis
May 24th, 2017
Patterned cortical tension mediated by N-cadherin controls cell geometric order in the Drosophila eye.
March 3rd, 2015
Direct laser manipulation reveals the mechanics of cell contacts in vivo.
October 29th, 2013
Principles of E-Cadherin Supramolecular Organization In Vivo.
August 17th, 2012
Bond flexibility and low valence promote finite clusters of self-aggregating particles.
December 1st, 2008
Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis.
October 10th, 2019
Experimental validation of force inference in epithelia from cell to tissue scale
November 27th, 2018
Distinct contributions of tensile and shear stress on E-cadherin levels during morphogenesis
October 12th, 2016
Laser Ablation to Probe the Epithelial Mechanics in Drosophila.
February 1st, 2016
Molecular clustering in the cell: from weak interactions to optimized functional architectures.
January 15th, 2016
Measuring forces and stresses in situ in living tissues.
July 22nd, 2015
Calcium Spikes in Epithelium: study on Drosophila early embryos.
January 8th, 2015
Superresolution measurements in vivo: imaging Drosophila embryo by photoactivated localization microscopy.
August 22nd, 2014
Probing cell mechanics with subcellular laser dissection of actomyosin networks in the early developing Drosophila embryo.
August 1st, 2014
Clustering of low-valence particles: structure and kinetics.
May 5th, 2014
Setting-up a simple light sheet microscope for in toto imaging of C. elegans development.
February 18th, 2014
Membrane microdomains: from seeing to understanding.
February 22nd, 2013
Cortical forces in cell shape changes and tissue morphogenesis.
May 1st, 2012
Calcium signaling in developing embryos: focus on the regulation of cell shape changes and collective movements.
March 2nd, 2011
FCS diffusion laws in two-phase lipid membranes: determination of domain mean size by experiments and Monte Carlo simulations.
January 1st, 2011
Force generation, transmission, and integration during cell and tissue morphogenesis.
December 23rd, 2010
Planar polarized actomyosin contractile flows control epithelial junction remodelling.
September 1st, 2009
Probing cell-surface dynamics and mechanics at different scales.
November 1st, 2008
Fluorescence fluctuations analysis in nanoapertures: physical concepts and biological applications.
September 1st, 2008
Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation.
June 5th, 2008
A two-tiered mechanism for stabilization and immobilization of E-cadherin.
August 1st, 2007
Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis.
July 26th, 2006
Dynamic molecular confinement in the plasma membrane by microdomains and the cytoskeleton meshwork.
December 30th, 2005
Fluorescence correlation spectroscopy diffusion laws to probe the submicron cell membrane organization
September 9th, 2005