Understanding the physical origin of cell and tissue shapes

FOR BEGINNERS

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.

FOR SPECIALISTS

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.