The initiation and propagation of Hes7 oscillation are cooperatively regulated by Fgf and notch signaling in the somite segmentation clock.
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.
Niwa
Yasutaka
Y
Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
Masamizu
Yoshito
Y
Liu
Tianxiao
T
Nakayama
Rika
R
Deng
Chu-Xia
CX
Kageyama
Ryoichiro
R
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001683:Biological Clocks / Q000187:drug effects; D002970:Cleavage Stage, Ovum / Q000187:drug effects / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D011758:Pyrroles / Q000494:pharmacology; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D019170:Somites / Q000187:drug effects / Q000378:metabolism*; D014280:Triglycerides / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D051792:Basic Helix-Loop-Helix Proteins; D005346:Fibroblast Growth Factors; D011758:Pyrroles; D051880:Receptors, Notch; D014280:Triglycerides; D005680:gamma-Aminobutyric Acid; C430525:Hes7 protein, mouse; C105686:SU 5402; C057077:1,2-dilinolenoyl-3-(4-aminobutyryl)propane-1,2,3-triol