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- Title
Notch activity acts as a sensor for extracellular calcium during vertebrate left-right determination.
- 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
- 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.
- Publication
Nature, 2004, Vol 427, Issue 6970, p121
- ISSN
1476-4687
- Publication type
Journal Article
- DOI
10.1038/nature02190