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Notch activity acts as a sensor for extracellular calcium during vertebrate left–right determination

Author

Listed:
  • Ángel Raya

    (The Salk Institute for Biological Studies)

  • Yasuhiko Kawakami

    (The Salk Institute for Biological Studies)

  • Concepción Rodríguez-Esteban

    (The Salk Institute for Biological Studies)

  • Marta Ibañes

    (The Salk Institute for Biological Studies)

  • Diego Rasskin-Gutman

    (The Salk Institute for Biological Studies)

  • Joaquín Rodríguez-León

    (Instituto Gulbenkian de Ciencia)

  • Dirk Büscher

    (The Salk Institute for Biological Studies)

  • José A. Feijó

    (Instituto Gulbenkian de Ciencia
    Faculdade de Ciencias, Universidade Lisboa)

  • Juan Carlos Izpisúa Belmonte

    (The Salk Institute for Biological Studies)

Abstract

During vertebrate embryo development, the breaking of the initial bilateral symmetry is translated into asymmetric gene expression around the node and/or in the lateral plate mesoderm. The earliest conserved feature of this asymmetric gene expression cascade is the left-sided expression of Nodal, which depends on the activity of the Notch signalling pathway. Here we present a mathematical model describing the dynamics of the Notch signalling pathway during chick embryo gastrulation, which reveals a complex and highly robust genetic network that locally activates Notch on the left side of Hensen's node. We identify the source of the asymmetric activation of Notch as a transient accumulation of extracellular calcium, which in turn depends on left–right differences in H+/K+-ATPase activity. Our results uncover a mechanism by which the Notch signalling pathway translates asymmetry in epigenetic factors into asymmetric gene expression around the node.

Suggested Citation

  • Ángel Raya & Yasuhiko Kawakami & Concepción Rodríguez-Esteban & Marta Ibañes & Diego Rasskin-Gutman & Joaquín Rodríguez-León & Dirk Büscher & José A. Feijó & Juan Carlos Izpisúa Belmonte, 2004. "Notch activity acts as a sensor for extracellular calcium during vertebrate left–right determination," Nature, Nature, vol. 427(6970), pages 121-128, January.
    • Handle: RePEc:nat:nature:v:427:y:2004:i:6970:d:10.1038_nature02190
    DOI: 10.1038/nature02190
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    Cited by:

    1. Stefano Ciliberti & Olivier C Martin & Andreas Wagner, 2007. "Robustness Can Evolve Gradually in Complex Regulatory Gene Networks with Varying Topology," PLOS Computational Biology, Public Library of Science, vol. 3(2), pages 1-10, February.

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