Our research Projects
Collaborations: Léo Guignard (LIS, CENTURI, Marseille), Alfonso Martinez Arias (Universidad Pompeu Fabra, Barcelona), Matthias Merkel (CPT, CENTURI, Marseille), Philippe Roudot (I2M, CENTURI, Marseille), Vikas Trivedi (EMBL, Barcelona).
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 & Trivedi, Nature Com. 2022).
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.
adapted from Chan, Shivakumar, 2017
Collaborations: Thomas Lecuit (IBDM, Marseille), Edwin Munro (Univ of Chicago), Jean-François Rupprecht (CPT, Marseille)
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, Scientific Reports 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.