De Renzis Group

Cell dynamics and signalling during morphogenesis

Previous and current research

Tissue morphogenesis is triggered by shape changes in single cells or group of cells. This remodelling depends on a complex interaction between cortical forces exerted by the actin cytoskeleton and membrane homeostasis (i.e. vesicular trafficking and lipid metabolism). Using the early Drosophila embryo as model organism, we wish to understand how membrane trafficking and cytoskeletal dynamics are regulated during morphogenesis and how this, in turn, impacts on specific cell and tissue behaviour.

We have recently developed new optogenetic methods to manipulate key components of the membrane transport machinery and cytoskeletal regulators with cellular precision in situ during embryonic development (Figure 1). Using these novel tools in combination with two-photon microscopy we can now control protein function with high-spatio temporal precision and thus functionally link subcellular to supracellular processes during morphogenesis. We are also implementing optogenetics to study signalling systems and induce tissue-specific differentiation programmes at will.

Future projects and goals

Using a combination of imaging, genome engineering, optogenetic, and biochemical approaches, we wish to elucidate how machineries controlling intracellular trafficking re-organise during differentiation and how this in turn impacts on global changes in tissue morphology. One long-term goal of the group will be to reconstitute morphogenetic processes in naïve tissues using synthetic approaches.

Surface view of a Drosophila embryo at the onset of gastrulation. A pulse of laser light has been used to trigger the translocation of an actin inhibitor to the plasma membrane in a central stripe of cells. Optogentically activated cells lose their regular hexagonal shape and will fail to gastrulate. Image is pseudo-coloured according to fluorescence intensity (blue=low/yellow=high). See also Movie 1.
Confocal movie of an embryo at the onset of gastrulation (surface view). Using a pulse of two-photon laser (red box), an inhibitor of actin polymerisation was recruited to the plasma membrane in a central stripe of cells. Activated cells cannot contract and are pulled by neighbouring non-activated contracting cells.