In a developing wing and through a technique called Clonal Analysis, the researchers manipulated groups of cells, among groups of normal cells, to remove Notch receptor expression. The scientists used the Drosophila wing because it is an excellent model to describe how cells behave when a certain gene is mutated and to determine and test how this mutation affects adjacent cells. This was the objective of the study designed by Isabelle Becam, post-doctoral researcher in Miln's Group and first author of the article. "As expected, the cells lacking Notch did not activate the pathway, but what was surprising was the observation that neighbouring cells did". Becam then questioned whether the absence of Notch in a group of mutated cells could cause activation.
Indeed, the analyses demonstrated that the Notch receptor sequesters the ligands and prevents these from connecting to the Notch receptors of adjoining cells. The experiments showed that the absence of the receptor in the mutated cells leaves many ligands free, ready to enter into contact with Notch receptors of the non-manipulated cells. "It is strange, but in the cell emitting the signal, Notch receptor captures the ligands by acting as a silencer while in the cell receiving the signal the binding of ligands with Notch allows activation of the pathway". "In fact", says Miln, "it is all to do with a fine balance between ligands and receptors of the emitting and receiving cell". In other words, Notch is a kind of double agent and exerts opposing functions: repressing or activating the pathway depending on whether it is located in cells emitting or receiving the signal. It must be noted that such a simple activation system involves multiple repression mechanisms, "because this is a crucial but also dangerous signalling pathway", explains Miln.
The researchers have discovered the self-repression mechanism of Notch in Drosophila and it
|Contact: Snia Armengou|
Institute for Research in Biomedicine (IRB Barcelona)