Vesicular Trafficking and Cell Signalling

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For a long time vesicular trafficking has been regarded only as a transport mechanism for proteins. However this view has dramatically evolved and vesicular trafficking is now known to be involved in many key developmental events like cell signalling and the establishment of cell polarity, but also in tumor formation.

Our group is using mainly the fruitfly (Drosophila melanogaster) as a model system to study how vesicular trafficking regulates cell signalling during development. In particular, we are interested in the role of endocytosis in the spatiotemporal control of receptor activity and signal transduction. We are presently focusing on two topics: Collective cell migration and Notch signalling.

Cell migration is a fascinating process that involves polarization of cells. Metastases form through the migration of cells from the primary tumor. Evidences accumulate that metastatic migrations are not performed by individual cells, but by cells migrating collectively. To study such collective cell migration we use the egg chamber of the fruit fly Drosophila, where a group of cell named border cells migrates as a small cluster. These cells are attracted through the activation of Receptor Tyrosine Kinases, and we have recently demonstrated that the activity of these receptors is polarized through the action of two distinct endocytic transport steps. We are currently further investigating this regulation. In particular, we want to understand how endocytosis regulates the formation of motile structure and how this is coordinated in a group, so that the entire cluster moves in the right direction. Furthermore, we want to determine if the molecular mechanisms identified are conserved in other system, such as other collective migrations in vivo in Drosophila and in mammals.

Notch signalling is a cell-cell signalling pathway conserved in all animal species studied so far. It is fundamental for development through the regulation of cell differentiation, cell proliferation and cell death. In particular, Notch plays an important role in the maintenance of stem cells and in the proper development of the mammalian hematopoietic system. We have previously involved the endocytic pathway in the regulation of the Notch ligand during asymmetric cell division in the peripheral nervous system of Drosophila. We are currently further investigating the role of endocytosis in the regulation of both the Notch receptor and the ligand during asymmetric cell division in vivo in flies, but also in mammalian cell culture assays.

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