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Approches physiques de la dynamique cellulaire et de la morphogenèse tissulaire

Nous cherchons à comprendre les principes physiques qui sous-tendent la morphogenèse des animaux. Pour ce faire, nous développons et appliquons des approches quantitatives pour observer, perturber et prévoir les mouvements morphogénétiques.

Notre travail porte sur des questions fondamentales de la morphogenèse des systèmes multicellulaires : comment les cellules génèrent, transmettent et répondent aux forces mécaniques, de l’échelle supramoléculaire à l’échelle multicellulaire ? Comment ces forces sont-elles couplées aux processus de signalisation et de différenciation cellulaires ? Comment les structures organisées et fonctionnelles émergent-elles de ces interactions ? Pour répondre à ces questions, nous nous concentrons sur trois aspects de la morphogenèse :

(1) L’organisation et la dynamique supramoléculaire des contacts cellulaires;

(2) La mécanique des contacts cellulaires et leur remodelage;

(3) Les changements d’état mécano-chimiques dans l’auto-organisation multicellulaire.

Nous développons des approches à la fois expérimentales et théoriques pour étudier plusieurs systèmes multicellulaires in vivo et in vitro : les embryons de drosophile et de C. elegans, et les organoïdes embryonnaires de souris. L’originalité de notre approche réside dans l’intégration à la fois de la physique (imagerie/mécanique/modélisation) et de la biologie expérimentale pour étudier la morphogenèse tissulaire de manière quantitative.

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Microscopie à fluorescence d'un embryon de C. elegans : membranes en cyan et histone en orange

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Membres de l'équipe

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Alumni

Ils ont contribué à nos activités
Hashmi Ali
Université d'Helsinki, boursier postdoctoral
Rulquin Charlotte
Marseille, professeur de lycée
Kong Weiyuan
Université de Paris, post-doctorant
Monika Ludanyi
Veracyte, Inc, chef d'équipe développement de produits
Girish Kale, Heidelberg
Boursier postdoctoral
Anaïs Baille, Dresde
Boursier postdoctoral
Eunice Chan
Université d'Aix Marseille, ingénieur
Olivier Loison
BearingPoint, Paris, data scientist
Pierre Mangeol
Université d'Aix Marseille, maître de conférences
Rémy Flores Flores
Toulouse, I2MC, chef de service imagerie
Olga Markova
Polytechnique LadHyX, boursier postdoctoral
Binh An Truongquang
Totalenergies Paris, lead data scientist
Jérémie Capoulade
Ingénieur système, Agence spatiale européenne, Pays-Bas
Matteo Rauzi
Université de Nice, France, chef de groupe

Les organismes qui nous financent

Ils soutiennent nos recherches
CENTURI
Fondation Recherche Medicale

ERC Synergy 2022 "Breakdance"

Galerie

fluorescence microscopy of a C. elegans embryo (membrane in magenta and Fizzled in cyan)
fluorescence microscopy of a C. elegans embryo (membrane in cyan and DNA in orange)
drosophila wing, spinning disk, 10X
illumination part of a home-made microscope
zoom on a part of the illumination setup of the lattice light sheet microscope

Approches physiques de la dynamique cellulaire et de la morphogenèse tissulaire

Mechanics of cell contacts and their remodelling

During tissue formation, cell contacts are remodelled by changes in adhesion forces and cell contractility (Lecuit and Lenne, Nature Rev Mol Cell Bio, 2007). To identify the nature of these forces and the mechanical properties of the contacts, we develop and apply physical methods such as laser nanodissection and optical tweezers micromanipulation (Bambardekar et al, PNAS 2015), which are now becoming widespread in the community. Quantification of cell shape changes induced by laser micromanipulation provides direct measurements of the forces acting at cell contacts, and reveals the viscoelastic properties of the tissue (Clément et al, Current Bio 2017). We have shown, using these methods, the distribution of forces (dependent on the molecular motor Myosin-II) that remodel cell contacts during epithelial morphogenesis (Rauzi, Nature Cell Bio 2008). We have shown the importance of geometry in the application of forces shaping cell contacts (Kale et al, Nature Comm 2018). We have highlighted the central role of viscous dissipation in cell and tissue shape changes (Clément et al, Current Bio 2017). The methods developed in our team, coupled with genetic perturbation and mechanical modeling, also reveal how adhesion molecules quantitatively control cell shapes by coupling to contractile forces (Chan, Shivakumar, eLife 2017).
With these approaches, we continue exploring several aspects of cell contact mechanics including the dynamic interplay of adhesion, biochemical signaling, and actomyosin contractility shapes cell contacts using Drosophila and C. elegans embryos as model systems.

Mechanochemical state changes in multicellular self-organization

The formation of multicellular organisms is based on symmetry breaking and tissue patterning events. Among these, the process of gastrulation transforms an apparently homogeneous group of cells into the outline of an organism with recognisable body axes and tissue layers. Our aim is to understand the organizational principles underlying the process of gastrulation in mammals, using an in vitro system composed of embryonic stem cells, called gastruloid. We have recently shown how differentiation, coupled with a change in the mechanical behavior of cells, generates large-scale flow, which in turn polarizes the multicellular system and defines distinct germ layers (Hashmi et al, eLife 2022). This mechanism is reminiscent of the process that occurs at the primitive streak in the embryo and has the characteristics of a mechanochemical phase transition (Lenne and Trivedi, Nature Comm 2022).

New approaches to tissue morphogenesis

Our team has developed and applied over the years several approaches to study cell dynamics and tissue morphogenesis. Such approaches include mechanical measurements and imaging methods. To probe the mechanics of cells in tissues, we introduced optical tweezers for direct manipulation of cell contacts (Bambardekar, PNAS 2015; Chardès et al, JOVE 2018). We have validated and implemented force inference methods in epithelia from cell and tissue scale (Kong et al, 2019, Code available here). We strive to implement long-term imaging methods, including light sheet and non-linear microscopy,  to image the multicellular choreography and the changes of biochemical states leading to the formation of tissues and organs.

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