Our research Projects



Collaborations: Alfonso Martinez Arias (Universidad Pompeu Fabra, Barcelona), Simon Gsell (IRPHE, CENTURI, Marseille), Léo Guignard (LIS, CENTURI, Marseille) , Matthias Merkel (CPT, CENTURI, Marseille), Philippe Roudot (I2M, CENTURI, Marseille), Olivier Theodoly (LAI, CENTURI, Marseille), Vikas Trivedi (EMBL, Barcelona), Virgile Viasnoff (CINAM, CENTURI, Marseille).

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.

Self-patterning of featherS in bird embryos

In 2023 we started a new project on the development of feathers on the dorsal skin of bird embryos. The feathers are formed from cellular aggregates that we can observe early in development, called primordia. These feather primordia do not form randomly inside the tissue, but they are distributed in a rather stereotypic fashion that is species-specific. Broadly speaking, we distinguish two types of bird species, based on the distribution of the feather primordia: some present a regular periodic pattern (e.g., chicken and quail), and some others present a more random distribution (e.g., ostrich and emu). We focus mainly on the first category, to understand the mechanisms that are responsible for the pattern regularity observed.

This system is particularly interested because there is a very close interplay between chemical cues (morphogens) and physical cues (stresses). The two kinds of cues mutually influence each other during the whole process, so it is very challenging to recognize the effect of one of the two aspects alone. Hence, thanks to the know-how of our group, we will investigate the role of the physical cues in the spontaneous emergence of the periodic patterns of feather primordia, by looking at the forces both at the level of the cell contacts and at larger scale.

Collaborations: Marie Manceau (CIRB, Collège de France, Paris).