De Renzis Group
Developmental modulation of intracellular trafficking during tissue morphogenesis
Cross-section of a developing Drosophila embryo showing polarised trafficking of Notch signaling components (ventral is down). The signaling receptor Notch is endocytosed (green dots) specifically in cells undergoing invagination (ventral furrow formation, mesoderm).
Previous and current research
Our research focuses on how cells reorganise their cyto-architecture during tissue morphogenesis. Using a combination of imaging techniques and biochemistry, the group aims to understand how changes in protein and membrane dynamics regulate changes in cell morphology and tissue movement during development.
The early Drosophila embryo provides an excellent system for our studies. In about 60 minutes a syncytium of ~6000 nuclei completes the process of cellularisation, a particular form of cytokinesis involving a massive mobilisation of intracellular membranes. Concomitantly, the embryo undergoes extensive remodelling of gene expression characterised by the activation of the zygotic genome and degradation of previously supplied maternal transcripts (maternal to zygotic transition). 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 has 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 mesoderm specific activation of Notch trafficking (see figure). Importantly, mesoderm specific trafficking patterns are not limited to Notch and Delta; many regulatory proteins involved in mesoderm morphogenesis show also similar trafficking patterns. It is likely that the mesoderm specific modulation of intracellular membrane dynamics represents a general regulatory principle operating during mesoderm morphogenesis.
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 in the early Drosophila embryo. Our long-term goal is to analyse the differentiation of intracellular pathways in other cell types and tissues as well. We wish to elucidate how machineries controlling intracellular trafficking reorient during differentiation and how this in turns impacts on global changes in tissue morphology.