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Notch signalling

A short cut to the nucleus

Nature volume 393, pages 304–305 (1998)Cite this article

Our bodies have a complicated structure, but the messages that pass between cells to coordinate the construction process are simple and few in kind. A handful of basic types of signal are used repeatedly, in different tissues and organisms, to direct cells along one developmental pathway or another according to the characters of their neighbours. The signalling mechanisms have been conserved in evolution and, if we are to understand development, we need to know how they work. A report by Schroeter and colleagues1 on page 382 of this issue, complemented by other studies appearing concurrently in Cell2 and in Current Biology3, settles an old controversy and gives a remarkably neat answer to the question of how the Notch signalling mechanism — one of the key modes of cell-cell communication in animal embryos — relays messages from the surface of a cell to the nucleus.

Notch is a transmembrane protein that acts as a signal receptor and is most famous for its function in neurogenesis4. Neuronal cells (neurons or committed neuroblasts) normally arise as isolated individuals within a sheet of non-neuronal cells. But when Notch signalling is defective, the neighbours of neuronal cells also develop as neuronal cells, producing an excess of neurons at the expense of other cell types. Studies in Drosophila, Caenorhabditis elegans and vertebrates have shown why. Nascent neuronal cells express a Notch ligand known as Delta, which is also a transmembrane protein. By binding to Notch in the membranes of the neighbouring cells, Delta normally delivers an inhibitory signal that prevents the neighbours from developing along the neuronal pathway. Where this lateral inhibition fails, adjacent cells behave in the same way; where it operates correctly, they are forced to be different.

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  1. the Imperial Cancer Research Fund, PO Box 123, WC2A 3PX, London, Lincolns Inn Fields, UK

    Julian Lewis

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Lewis, J. A short cut to the nucleus. Nature 393, 304–305 (1998). https://doi.org/10.1038/30597

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