1. Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
2. Instituto Gulbenkian de Ciencia, Rua Da Quinta Grande n6, 2780-901 Oeiras, Portugal
3. Centro de Biotecnologia Vegetal, Faculdade de Ciencias, Universidade Lisboa, 1749-016 Lisboa, Portugal
4. These authors contributed equally to this work

Correspondence to: Juan Carlos Izpisúa Belmonte¹ Email: belmonte@salk.edu

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.

1. Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
2. Instituto Gulbenkian de Ciencia, Rua Da Quinta Grande n6, 2780-901 Oeiras, Portugal
3. Centro de Biotecnologia Vegetal, Faculdade de Ciencias, Universidade Lisboa, 1749-016 Lisboa, Portugal
4. These authors contributed equally to this work

Correspondence to: Juan Carlos Izpisúa Belmonte¹ Email: belmonte@salk.edu

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