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

Ángel Raya, Yasuhiko Kawakami, Concepción Rodríguez-Esteban, Marta Ibañes, Diego Rasskin-Gutman, Joaquín Rodríguez-León, Dirk Büscher, José A. Feijó and Juan Carlos Izpisúa Belmonte ()
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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
Juan Carlos Izpisúa Belmonte: The Salk Institute for Biological Studies

Nature, 2004, vol. 427, issue 6970, 121-128

Abstract: 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.

Date: 2004
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DOI: 10.1038/nature02190

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