Forces mécaniques et morphogenèse des tissus

Nous autres créatures vivantes interagissons avec le monde extérieur au travers de cinq sens, deux desquels sont basés sur des stimulus mécaniques (toucher et ouïe) et deux autres sur des stimulus chimiques (odorat et goût). Tout laisse penser que nos cellules peuvent aussi répondre à ces stimuli, cependant on ignore presque tout de la réponse cellulaire aux signaux mécaniques.

Notre équipe explore les lois qui gouvernent ces réponses en cherchant à répondre aux questions suivantes :

  • Quelles forces mécaniques permettent de déformer les cellules chez un embryon ?
  • Quel est l’éventail des réponses cellulaires à un stimulus mécaniques ?
  • Un stimulus mécanique peut-il, comme un signal chimique, devenir un signal entre deux tissus ?
  • Comment les cellules résistent-elles aux stress mécaniques sans subir un dommage irréversible ?

Nous utilisons principalement le nématode C. elegans dont l’embryon s’allonge très rapidement en l’absence de toute division cellulaire. Nous combinons analyse génétique (RNA interférence, cribles génétiques), des méthodes modernes d’imagerie (nano-ablation par laser, microscopie rapide, FRET, analyse d’images), ainsi que des concepts de physique.

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We work at the interface between developmental biology and physics, focusing on epithelial tissues, which form the architecture of most of our organs. Our ultimate goal is to understand how the laws of physics account for cytoskeleton and junction remodelling to trigger cell shape changes and enable embryo/organ morphogenesis.

Using the C. elegans model, we combine molecular genetics and modern imaging methods to analyse how the embryo elongates. Cell shape changes, rather than cell division or cell intercalation, drive embryonic elongation. The first part of this 3-hour long process solely depends on the epidermis, the second on an interaction between the epidermis and muscles.

Over the past years we contributed to define how proper positioning and assembly of adherens junctions (CeAJs) and hemidesmosome-like junctions (CeHDs) is critical for elongation. We have started to dissect the role of forces by analysing the relative mechanical contribution of the various epidermal sub-types to elongation, and through a continuum mechanics model of elongation. More recently, we brought the concept of communication between different cell types through mechanotransduction, and established that CeHDs are mechanical signalling platforms.

We have also studied how the excretory tube, which ensures osmotic homeostasis of the animal, elongates. We established that small changes in osmotic pressure promote vesicle fusion to allow extension of the luminal membrane.

Résultats importants

  • CeHDs: We showed how plectin/BPAG1e and BPAG1a homologues encoded by vab-10 maintain epidermal integrity against mechanical stress during elongation. Thereby, we contributed to define the nature of CeHDs attaching the epidermis to the ECM, and identified several proteins promoting their biogenesis.
  • Mechanotransduction: We found that CeHDs are sensitive to mechanical forces and transduce such forces into a signalling process during morphogenesis that helps remodel the cytoskeleton and junctions.
  • Forces in morphogenesis: We identified several pathways controlling myosin II activity, and found that myosin II is mainly active in a subset of cells. Modelling in collaboration with physicists has confirmed some of our genetic data.
  • Excretory tube: Using advanced electron microscopy approaches, we revealed that extension of this unicellular tube depends on the recruitment of peri-apical vesicles, which fuse with the lumen when osmotic conditions change.
  • Exosomes: We characterized the first transmembrane complex acting in apical trafficking. By doing so, we showed that apical secretion of some proteins involves the release of exosomes from multivesicular bodies, which is mediated by the V0 sector of the V-ATPase.


Today, in connection with the past analysis of cell shape changes and secretion, the lab will focus on the input of physical forces in morphogenesis. My view is that physics is at the crossroads of cell and developmental biology, and will provide major input to interpret key biological processes. It offers very important perspectives for the decade to come.

We will set forth to do so in coming years along the following lines:

  • Develop a mesoscopic model of elongation accounting for how mechanical forces drive embryonic elongation
  • Define the cellular process influenced by mechanical forces and work out the molecular pathway(s) involved in cell shape changes

The added value of C. elegans is to offer a physiological environment in which to study the input of forces, along with powerful genetic tools. The combination of active and resistance forces typifying the elongating worm embryo would be very difficult to reproduce in a cell culture system. In addition, C. elegans embryos offer much greater simplicity than most other live systems.


  • Daniel Riveline: ISIS/ IGBMC, Strasbourg (France); stretching device and micro-patterning.
  • Martine Ben Amar: LPS – ENS, Paris 5france); modeling.
  • Stephan Grill: Biotec, Dresden (Germany); modelling and fast imaging.
  • Gene Myers: MPI-CBG, Dresden (Germany); Light-sheet Microscopy.