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

Author

Listed:
  • 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)

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.

Suggested Citation

  • David Sprinzak & Amit Lakhanpal & Lauren LeBon & Leah A. Santat & Michelle E. Fontes & Graham A. Anderson & Jordi Garcia-Ojalvo & Michael B. Elowitz, 2010. "Cis-interactions between Notch and Delta generate mutually exclusive signalling states," Nature, Nature, vol. 465(7294), pages 86-90, May.
    • Handle: RePEc:nat:nature:v:465:y:2010:i:7294:d:10.1038_nature08959
    DOI: 10.1038/nature08959
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    Cited by:

    1. Xiaochan Xu & Philip Allan Seymour & Kim Sneppen & Ala Trusina & Anuska la Rosa Egeskov-Madsen & Mette Christine Jørgensen & Mogens Høgh Jensen & Palle Serup, 2023. "Jag1-Notch cis-interaction determines cell fate segregation in pancreatic development," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Sophie K Kay & Heather A Harrington & Sarah Shepherd & Keith Brennan & Trevor Dale & James M Osborne & David J Gavaghan & Helen M Byrne, 2017. "The role of the Hes1 crosstalk hub in Notch-Wnt interactions of the intestinal crypt," PLOS Computational Biology, Public Library of Science, vol. 13(2), pages 1-28, February.

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