title: The period of the somite segmentation clock is sensitive to Notch activity.
abstract: The number of vertebrae is defined strictly for a given species and depends on the number of somites, which are the earliest metameric structures that form in development. Somites are formed by sequential segmentation. The periodicity of somite segmentation is orchestrated by the synchronous oscillation of gene expression in the presomitic mesoderm (PSM), termed the "somite segmentation clock," in which Notch signaling plays a crucial role. Here we show that the clock period is sensitive to Notch activity, which is fine-tuned by its feedback regulator, Notch-regulated ankyrin repeat protein (Nrarp), and that Nrarp is essential for forming the proper number and morphology of axial skeleton components. Null-mutant mice for Nrarp have fewer vertebrae and have defective morphologies. Notch activity is enhanced in the PSM of the Nrarp(-/-) embryo, where the ~2-h segmentation period is extended by 5 min, thereby forming fewer somites and their resultant vertebrae. Reduced Notch activity partially rescues the Nrarp(-/-) phenotype in the number of somites, but not in morphology. Therefore we propose that the period of the somite segmentation clock is sensitive to Notch activity and that Nrarp plays essential roles in the morphology of vertebrae and ribs.
authors.affiliation: Laboratory of Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
authors.forename: Woong
authors.initials: W
authors.lastname: Kim
authors.forename: Takaaki
authors.initials: T
authors.lastname: Matsui
authors.forename: Masataka
authors.initials: M
authors.lastname: Yamao
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishibashi
authors.forename: Kota
authors.initials: K
authors.lastname: Tamada
authors.forename: Toru
authors.initials: T
authors.lastname: Takumi
authors.forename: Kenji
authors.initials: K
authors.lastname: Kohno
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Oba
authors.forename: Shin
authors.initials: S
authors.lastname: Ishii
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sakumura
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Bessho
mesh_terms: D000818:Animals; D001683:Biological Clocks; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D011859:Radiography; D051880:Receptors, Notch / Q000378:metabolism*; D019170:Somites / Q000378:metabolism*; D013131:Spine / Q000000981:diagnostic imaging / Q000196:embryology*; D015854:Up-Regulation
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C499040:Nrarp protein, mouse; D011506:Proteins; D051880:Receptors, Notch