FGF signaling acts upstream of the NOTCH and WNT signaling pathways to control segmentation clock oscillations in mouse somitogenesis.
Fibroblast growth factor (FGF) signaling plays a crucial role in vertebrate segmentation. The FGF pathway establishes a posterior-to-anterior signaling gradient in the presomitic mesoderm (PSM), which controls cell maturation and is involved in the positioning of segmental boundaries. In addition, FGF signaling was shown to be rhythmically activated in the PSM in response to the segmentation clock. Here, we show that conditional deletion of the FGF receptor gene Fgfr1 abolishes FGF signaling in the mouse PSM, resulting in an arrest of the dynamic cyclic gene expression and ultimately leading to an arrest of segmentation. Pharmacological treatments disrupting FGF signaling in the PSM result in an immediate arrest of periodic WNT activation, whereas NOTCH-dependent oscillations stop only during the next oscillatory cycle. Together, these experiments provide genetic evidence for the role of FGF signaling in segmentation, and identify a signaling hierarchy controlling clock oscillations downstream of FGF signaling in the mouse.
Wahl
Matthias B
MB
Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Deng
Chuxia
C
Lewandoski
Mark
M
Pourquié
Olivier
O
D000818:Animals; D001683:Biological Clocks / Q000235:genetics; D002970:Cleavage Stage, Ovum / Q000378:metabolism / Q000502:physiology*; D004622:Embryo, Mammalian; D005260:Female; D005346:Fibroblast Growth Factors / Q000502:physiology*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D011247:Pregnancy; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D051880:Receptors, Notch / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D019170:Somites / Q000196:embryology* / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D051153:Wnt Proteins / Q000378:metabolism / Q000502:physiology*
D051880:Receptors, Notch; D051153:Wnt Proteins; D014212:Tretinoin; D005346:Fibroblast Growth Factors; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1