Abstract
Periodic formation of somites is controlled by the segmentation clock, where the oscillator Hes7 regulates cyclic expression of the Notch modulator Lunatic fringe. Here, we show that Hes7 also regulates cyclic expression of the Fgf signaling inhibitor Dusp4 and links Notch and Fgf oscillations in phase. Strikingly, inactivation of Notch signaling abolishes the propagation but allows the initiation of Hes7 oscillation. By contrast, transient inactivation of Fgf signaling abolishes the initiation, whereas sustained inactivation abolishes both the initiation and propagation of Hes7 oscillation. We thus propose that Hes7 oscillation is initiated by Fgf signaling and propagated/maintained anteriorly by Notch signaling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism*
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Biological Clocks* / drug effects
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Cleavage Stage, Ovum / drug effects
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Cleavage Stage, Ovum / metabolism*
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Fibroblast Growth Factors / antagonists & inhibitors
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Fibroblast Growth Factors / metabolism*
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Gene Expression Regulation, Developmental / drug effects
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Mice
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Mice, Knockout
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Models, Biological
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Mutation / genetics
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Pyrroles / pharmacology
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Receptors, Notch / antagonists & inhibitors
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Receptors, Notch / metabolism*
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Signal Transduction* / drug effects
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Somites / drug effects
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Somites / metabolism*
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Triglycerides / pharmacology
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gamma-Aminobutyric Acid / analogs & derivatives
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gamma-Aminobutyric Acid / pharmacology
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Hes7 protein, mouse
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Pyrroles
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Receptors, Notch
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SU 5402
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Triglycerides
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gamma-Aminobutyric Acid
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Fibroblast Growth Factors
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1,2-dilinolenoyl-3-(4-aminobutyryl)propane-1,2,3-triol