De Renzis Group
Membrane dynamics during tissue morphogenesis and differentiation
Cross-section of a developing Drosophila embryo showing polarised trafficking of Notch signalling components (ventral is down). The signalling receptor Notch is endocytosed (green dots) together with its ligand Delta (blue dots), specifically in cells undergoing invagination (ventral furrow formation)
The de Renzis group investigates how the machinery that controls trafficking within cells is reorganised as tissues form, and how that affects embryonic development.
Previous and current research
Our research is focused on understanding how machineries controlling intracellular trafficking are re-organised during cell and tissue morphogenesis and how this, in turn, impacts on specific cell and tissue behavior during embryonic development. We address these questions using the early Drosophila embryo as a model system during cellularisation and early gastrulation stages.
Cellularisation of the Drosophila embryo provides an excellent system to study mechanisms linking membrane trafficking and cell/tissue morphogenesis. It takes around an hour for a syncytium of ~6000 nuclei to complete the process of cellularisation, a particular form of cytokinesis involving a massive mobilisation of intracellular membranes. The end result of this process is the formation of a fully polarised ephitelium. Concomitantly, the embryo undergoes extensive remodelling of gene expression characterised by the activation of zygotic transcription. This transition immediately precedes gastrulation, when tissue differentiation becomes increasingly dramatic. Because zygotic transcription is required for cellularisation, it can directly influence the differentiation of the plasma membrane by differentially regulating the distribution of proteins and lipids in different cell types.
We have developed a system based on chromosomal rearrangements and microarrays that have allowed, for the first time, the identification of the entire set of zygotic genes active at cellularisation. We have applied this approach to identify the genes controlling the polarised activation of Notch trafficking in the early embryo (see figure). We are now combining high-resolution imaging methods to follow the spatio-temporal modulation of trafficking pathways in live Drosophila embryos at the subcellular scale.
Future projects and goals
Using a combination of imaging, genetics and biochemical approaches we wish to identify the cell biological basis underlying the pathways controlling changes in membrane dynamics during morphogenesis. Our long-term goal is to analyse the differentiation of intracellular pathways in other cell types and tissues. We wish to elucidate how machineries controlling intracellular trafficking reorient during differentiation and how this in turn impacts on global changes in tissue morphology.