Wnt3a plays a major role in the segmentation clock controlling somitogenesis.
The vertebral column derives from somites generated by segmentation of presomitic mesoderm (PSM). Somitogenesis involves a molecular oscillator, the segmentation clock, controlling periodic Notch signaling in the PSM. Here, we establish a novel link between Wnt/beta-catenin signaling and the segmentation clock. Axin2, a negative regulator of the Wnt pathway, is directly controlled by Wnt/beta-catenin and shows oscillating expression in the PSM, even when Notch signaling is impaired, alternating with Lfng expression. Moreover, Wnt3a is required for oscillating Notch signaling activity in the PSM. We propose that the segmentation clock is established by Wnt/beta-catenin signaling via a negative-feedback mechanism and that Wnt3a controls the segmentation process in vertebrates.
Aulehla
Alexander
A
Abteilung Entwicklungsbiologie, Max-Planck-Institut für Immunbiologie, Stübeweg 51, D-79108, Freiburg, Germany.
Wehrle
Christian
C
Brand-Saberi
Beate
B
Kemler
Rolf
R
Gossler
Achim
A
Kanzler
Benoit
B
Herrmann
Bernhard G
BG
D000818:Animals; D060466:Axin Protein; D001683:Biological Clocks / Q000235:genetics / Q000502:physiology*; D019521:Body Patterning / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000196:embryology* / Q000378:metabolism; D004625:Embryo, Nonmammalian; D005246:Feedback / Q000502:physiology; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D019170:Somites / Q000166:cytology / Q000378:metabolism*; D013131:Spine / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014714:Vertebrates / Q000196:embryology* / Q000378:metabolism; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin
D060466:Axin Protein; C111729:Axin2 protein, mouse; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D051176:beta Catenin; C064045:delta protein; D016695:Glycosyltransferases; C498392:Lfng protein, mouse