Spyros Artavanis-Tsakonas Lab

WELCOME TO THE ARTAVANIS LAB

Acquisition of specific cell fates during development depends on an intricate interplay of signalling pathways. Using Drosophila as our main experimental system we have been dissecting and studying a developmentally fundamental and evolutionary conserved cell signalling mechanism, the Notch pathway. Mutations in Notch signalling result in the abnormal development of a very broad spectrum of structures in Drosophila while Notch signalling malfunction in humans has been associated with specific pathologies including neoplastic conditions. The central element of this signalling pathway is the Notch surface receptor. A signal through Notch does not seem to convey specific instructions to the cell but rather modulates the ability of a non-terminally differentiated cell to receive and/or interpret developmental signals that result in differentiation, proliferation or even apoptosis. The Notch pathway is thus a fundamental regulator of cell fates in development, which is functionally and structurally conserved in metazoans and in general links the fate of one cell to that of its cellular neighbour through the interaction of the Notch surface receptor with membrane-bound ligands on the adjacent cell.

Using genetic and molecular approaches we have been studying this signaling mechanism at different levels. We are interested in understanding mechanistic aspects of the various steps that are essential for transmitting the extracellular signal to the nucleus as well as the controlling circuitry that can modulate Notch signal activity. We are using both mice and Drosophila not only to address the conservation of biological principles across species but also to take advantage of the distinct experimental approaches each system offers.

Genomic and genetic approaches are employed to identify the genetic circuitry that can modulate Notch signaling and examine how Notch signals integrate their action with other cell signalling pathways. We are particularly interested to ask if there are underlying rules that govern signalling crosstalk across tissues and across species. We have a long-standing interest to use Drosophila genetics as a tool to address problems relevant to human biology and have recently been using Drosophila to model and dissect Spinal Muscular Atrophy. We are also using mouse transgenesis on one hand to model a Notch related neurodegenerative disease that is associated with ischemic strokes and vascular dementia and on the other to examine the involvement of Notch in mammary gland carcinogenesis and intestinal development in mammals.