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Cis-interactions between Notch and Delta generate mutually exclusive signalling states

David Sprinzak, Amit Lakhanpal, Lauren LeBon, Leah A. Santat, Michelle E. Fontes, Graham A. Anderson, Jordi Garcia-Ojalvo and Michael B. Elowitz ()
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David Sprinzak: Howard Hughes Medical Institute, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA
Amit Lakhanpal: Howard Hughes Medical Institute, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA
Lauren LeBon: Howard Hughes Medical Institute, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA
Leah A. Santat: Howard Hughes Medical Institute, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA
Michelle E. Fontes: Howard Hughes Medical Institute, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA
Graham A. Anderson: Stanford University School of Medicine, 269 Campus Drive, Stanford, California 94305, USA
Jordi Garcia-Ojalvo: Universitat Politècnica de Catalunya, Colom 11, E-08222 Terrassa, Spain
Michael B. Elowitz: Howard Hughes Medical Institute, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA

Nature, 2010, vol. 465, issue 7294, 86-90

Abstract: Notch–delta cell-fate decisions The Notch–Delta signal transduction pathway is critical for many processes in development and disease, with a particular role in generating distinct cell fates among groups of initially equivalent cells and sharply defining neighbouring regions in developing tissues. Recent research has provided an increasingly comprehensive list of components and molecular interactions underlying Notch signalling, without revealing how these two proteins lead to clear cell-fate decisions. Sprinzak et al. use quantitative time-lapse microscopy to show that Notch levels in a given cell are ultrasensitive to the amount of Delta present at the surface of the same cell — as opposed to that exposed by its neighbours. This abrupt molecular switch means that a cell becomes exclusively a sender of Delta signalling (with high Delta and low Notch) or a receiver (vice versa). Numerical modelling shows how this new design principle enhances the sharpness of developmental boundaries set by classical lateral inhibition.

Date: 2010
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DOI: 10.1038/nature08959

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