Cell-cell interactions and notch signalling pathways

Participants :

Spyros Artavanis-Tsakonas, organisateur (MGH Cancer Center, Harvard Medical School, USA), Seth Blair (University of Wisconsin, USA), Sarah Bray (University of Cambridge, UK), Chirstos Delidakis (Institute of Molecular Biology and Biotechnology, Greece), Silvia Fre (MGH Cancer Center, USA), Walter Gehring, organisateur (Biozentrum, University of Bale, Switzerland), Tasuku Honjo (Kyoto University, Japan), David Ish-Horowicz (Imperial Cancer Research Fund, UK), Alain Israel (Pasteur Institute, France), Tom Kadesch (University of Pennsylvania School of Medicine, HHMI, USA), Chris Kintner (The Salk Institute for Biological Studies, USA), Raphaël Kopan (Washington University School of Medicine, USA), Julian Lewis (ICRF, UK), Angeliki Louvi (ENS Paris, France), Marc Muskavitch (Indiana University, USA), Norbert Perrimon (Harvard Medical School, USA), James Posakony (University of California San Diego, USA), Olivier Pourquié (LGPD-IBDM, France)

A la suite de cette rencontre, parution de l’article « Notch Signaling: Cell Fate Control and Signal Integration in Development » dans la revue Science (Science  30 Apr 1999: Vol. 284, Issue 5415, pp. 770-776 – DOI: 10.1126/science.284.5415.770)

Compte rendu de Walter Gehring

« Notch signalling » in Les Treilles: a colloquium organized by Spyros Artavanis-Tsakonas, 8 – 14 May, 1999

In 1915, a mutation in the fruitfly with wing notches was found and named Notch, that has provided a key to our understanding of how cells ≠ signal to one another, how they communicate. The Notch gene and other genes involved in Notch signalling have been conserved during evolution and are found in all animals and also in humans. The protein molecule encoded by the Notch gene serves as a Receptor which is localized on the cell surface. A neighboring cell may carry the Ligand molecules, Delta and Serrate, on their surfaces. When the two cells come into close contact “kissing each other”), the Ligand binds to the Notch receptor and triggers a cascade of events called Notch Signalling, which transmits the signal from the cell surface to the cell nucleus where it elicits changes in the activity of certain garget genes. These changes in gene activity can lead to changes in cell fate. For example, during the formation of the nervous system, a cell has to decide whether to become a nerve cell or an epidermis cell. Notch is involved in this decision. Once a cell has entered the nerve cell pathway, Notch signalling prevents the neighboring cells from entering the nerve cell pathway and to become epidermal cells instead. By inactivating Notch, all cells turn into nerve cells and the embryo dies.

Notch signalling has become a major area of developmental biology with ramifications into tumor biology. Specialists from all over Europe, the United States and Japan met in Les Treilles to discuss the general aspects of Notch signalling as well as the detailed mechanism of Notch action. In the beautiful and relaxed ambiance of Les Treilles, the most lively discussions and provocative presentations were put forward, including the first demonstration in Drosophila that a fragment a Notch molecule can translocate from the cell surface to the nucleus, that Notch can induce cell fate changes leading to the formation of wings and legs on the head of the fly, and that Notch is also involved in forming boundaries, like the wing margin, via a complicated network of genetic interactions. All participants were highly satisfied with the colloquium and received numerous new ideas for further experimentation. The stimulating atmosphere and the “esprit of Les Treilles” is quite unique.  W. G

Communications présentées :

Spyros Artavanis-Tsakonas – Notch: a general tool for cell fate control

Seth Blair – Notch, compartments and boudaries

Sarah Bray – Intersection of Notch and other signalling pathways

Christos Delidakis – Transcriptional control by enhancer of split proteins

Walter Gehring – Notch signalling in eye development and transdetermination

Tasuku Honjo – Protealytic cleavage of the Notch receptor by interaction with the ligand & Molecular mechanism of Notch signaling in cultured cells

David Ish-Horowicz – Cell asymmetries

Alain Israel – Ex vivo analysis of the mammalian Notch signaling pathway

Tom Kadesch – Transcriptional events downstream of Notch

Chris Kintner – Targets of Notch signaling during Xenopus development

Raphaël Kopan – Proteolytic Processing in Notch signaling: A protease revealed?

Julian Lewis – Notch signalling and pattern formation in vertebrate fissnes

Marc Muskavitch – Regulation of Delta signalling in Drosophila

Norbert Perrimon – Role of Glycosylation in Notch signaling

James Posakony – The Notch pathway and cell fate specification in the Drosophila PNS

Olivier Pourquié – Links between the Notch pathway and the clock linked to segmentation in vertebrates

 

 

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