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 types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Avian Proteins
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Body Patterning* / drug effects
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Calcium Signaling* / drug effects
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Calcium-Binding Proteins
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Cell Line, Tumor
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Chick Embryo
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Egtazic Acid / analogs & derivatives*
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Egtazic Acid / pharmacology
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Gastrula / metabolism
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Gene Expression Regulation, Developmental / drug effects
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Glycosyltransferases / genetics
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Glycosyltransferases / metabolism
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H(+)-K(+)-Exchanging ATPase / metabolism
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Humans
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Ligands
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Models, Biological
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Nodal Protein
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Omeprazole / pharmacology
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Proteins / genetics
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Proteins / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptor, Notch1
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Receptors, Notch
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Serrate-Jagged Proteins
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Transcription Factors*
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism
Substances
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Avian Proteins
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Calcium-Binding Proteins
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Ligands
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Membrane Proteins
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NODAL protein, human
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NOTCH1 protein, human
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Nodal Protein
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Proteins
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RNA, Messenger
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Receptor, Notch1
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Receptors, Cell Surface
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Receptors, Notch
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Serrate-Jagged Proteins
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Transcription Factors
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Transforming Growth Factor beta
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delta protein
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Egtazic Acid
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Glycosyltransferases
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LFNG protein, Gallus gallus
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LFNG protein, human
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H(+)-K(+)-Exchanging ATPase
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1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
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Omeprazole