Notch activity acts as a sensor for extracellular calcium during vertebrate left-right determination |
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Authors: | Raya Angel Kawakami Yasuhiko Rodríguez-Esteban Concepción Ibañes Marta Rasskin-Gutman Diego Rodríguez-León Joaquín Büscher Dirk Feijó José A Izpisúa Belmonte Juan Carlos |
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Affiliation: | Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA. |
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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. |
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