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Spatial and Temporal Dynamics of the Notch Ligand Delta During Development in Drosophila Melagonaster

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Unravelling developmental cues

European researchers worked to elucidate the mechanisms involved in the regulation of Notch signalling during development. By focusing on the internalisation of the Notch ligand Delta, they provided important information on the dynamics of signalling and its potential link with disease.

Health

During development, one of the central signal transduction pathways implicated in the determination of cell fate is the Notch pathway. Signalling through the Notch receptors has been highly conserved through evolution. It mediates cell communication and essentially drives cell differentiation early in life. Given its involvement in many diseases including cancer, stroke and Alzheimer's disease, understanding how Notch signalling works is of high medical relevance. Scientists of the EU-funded DELTA project used the fruit fly Drosophila melanogaster to study the mechanism of action of central players in this pathway, like Delta. The Notch ligand Delta is also a transmembrane protein which requires specific modifications to accommodate signal transduction. Experimental evidence surprisingly suggests that Delta proteins need to be cleared from the membrane to exert a mechanical force on the Notch receptor in the adjacent cell. To investigate the intracellular fate of the Delta proteins after internalisation, researchers fused it with a fluorescent red protein. Through time-lapse confocal microscopy, they were able to detect Delta within different cellular compartments at different stages of larva development. Genetic studies revealed the modification enzymes essential for Delta endocytosis and recycling, and the stage during internal trafficking where Delta exerts its function on the Notch receptor. Taken together, the findings of the DELTA study provide important insight on the Notch signalling pathway. Besides advancing our understanding on the dynamic nature of Delta molecules, this information could form the basis to study the implication of Delta in Notch-related pathologies.

Keywords

Notch signalling, Delta, pathway, receptor, Alzheimer's, Drosophila, transduction, microscopy, enzymes, endocytosis, pathologies

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