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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Journal of Theoretic...arrow_drop_down
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Journal of Theoretical Biology
Article . 2008 . Peer-reviewed
License: Elsevier TDM
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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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Article . 2008
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Modeling the segmentation clock as a network of coupled oscillations in the Notch, Wnt and FGF signaling pathways

Modeling the segmentation clock as a network of coupled oscillations in the notch, Wnt and FGF signaling pathways
Authors: Goldbeter, Albert; Pourquié, Olivier;

Modeling the segmentation clock as a network of coupled oscillations in the Notch, Wnt and FGF signaling pathways

Abstract

The formation of somites in the course of vertebrate segmentation is governed by an oscillator known as the segmentation clock, which is characterized by a period ranging from 30 min to a few hours depending on the organism. This oscillator permits the synchronized activation of segmentation genes in successive cohorts of cells in the presomitic mesoderm in response to a periodic signal emitted by the segmentation clock, thereby defining the future segments. Recent microarray experiments [Dequeant, M.L., Glynn, E., Gaudenz, K., Wahl, M., Chen, J., Mushegian, A., Pourquie, O., 2006. A complex oscillating network of signaling genes underlies the mouse segmentation clock. Science 314, 1595-1598] indicate that the Notch, Wnt and Fibroblast Growth Factor (FGF) signaling pathways are involved in the mechanism of the segmentation clock. By means of computational modeling, we investigate the conditions in which sustained oscillations occur in these three signaling pathways. First we show that negative feedback mediated by the Lunatic Fringe protein on intracellular Notch activation can give rise to periodic behavior in the Notch pathway. We then show that negative feedback exerted by Axin2 on the degradation of beta-catenin through formation of the Axin2 destruction complex can produce oscillations in the Wnt pathway. Likewise, negative feedback on FGF signaling mediated by the phosphatase product of the gene MKP3/Dusp6 can produce oscillatory gene expression in the FGF pathway. Coupling the Wnt, Notch and FGF oscillators through common intermediates can lead to synchronized oscillations in the three signaling pathways or to complex periodic behavior, depending on the relative periods of oscillations in the three pathways. The phase relationships between cycling genes in the three pathways depend on the nature of the coupling between the pathways and on their relative autonomous periods. The model provides a framework for analyzing the dynamics of the segmentation clock in terms of a network of oscillating modules involving the Wnt, Notch and FGF signaling pathways.

Keywords

Notch, Fibroblast Growth Factors -- physiology, Embryonic Development, Models, Biological, Feedback, Somitogenesis, Wnt, Segmentation, somitogenesis, Intercellular Signaling Peptides and Proteins -- physiology, Models, Biological Clocks, Receptors, Somites -- embryology, Chimie, FGF, Animals, Signal Transduction -- physiology, Physiological -- physiology, Notch -- physiology, Kinetics in biochemical problems (pharmacokinetics, enzyme kinetics, etc.), Body Patterning, Feedback, Physiological, model, Receptors, Notch, segmentation, oscillation, Biological, Embryonic Development -- physiology, Body Patterning -- physiology, Fibroblast Growth Factors, Wnt Proteins, Oscillation, Somites, Biological Clocks -- physiology, Wnt Proteins -- physiology, Intercellular Signaling Peptides and Proteins, Model, Signal Transduction

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
158
Top 10%
Top 10%
Top 1%
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