Abstract
Left-sided expression of Nodal in the lateral plate mesoderm is a conserved feature necessary for the establishment of normal left-right asymmetry during vertebrate embryogenesis. By using gain- and loss-of-function experiments in zebrafish and mouse, we show that the activity of the Notch pathway is necessary and sufficient for Nodal expression around the node, and for proper left-right determination. We identify Notch-responsive elements in the Nodal promoter, and unveil a direct relationship between Notch activity and Nodal expression around the node. Our findings provide evidence for a mechanism involving Notch activity that translates an initial symmetry-breaking event into asymmetric gene expression.
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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Body Patterning / physiology*
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Enhancer Elements, Genetic
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Gene Expression Regulation / physiology*
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Hedgehog Proteins
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Membrane Proteins / physiology*
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Mice
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Nodal Protein
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Organizers, Embryonic / physiology
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Promoter Regions, Genetic
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Receptors, Notch
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Signal Transduction / physiology
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Situs Inversus / embryology
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transforming Growth Factor beta / genetics*
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Transforming Growth Factor beta / metabolism
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Zebrafish / embryology
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Zebrafish / genetics
Substances
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Hedgehog Proteins
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Membrane Proteins
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Nodal Protein
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Nodal protein, mouse
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Receptors, Notch
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Trans-Activators
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Transforming Growth Factor beta