title: Setting the tempo in development: an investigation of the zebrafish somite clock mechanism.
abstract: The somites of the vertebrate embryo are clocked out sequentially from the presomitic mesoderm (PSM) at the tail end of the embryo. Formation of each somite corresponds to one cycle of oscillation of the somite segmentation clock--a system of genes whose expression switches on and off periodically in the cells of the PSM. We have previously proposed a simple mathematical model explaining how the oscillations, in zebrafish at least, may be generated by a delayed negative feedback loop in which the products of two Notch target genes, her1 and her7, directly inhibit their own transcription, as well as that of the gene for the Notch ligand DeltaC; Notch signalling via DeltaC keeps the oscillations of neighbouring cells in synchrony. Here we subject the model to quantitative tests. We show how to read temporal information from the spatial pattern of stripes of gene expression in the anterior PSM and in this way obtain values for the biosynthetic delays and molecular lifetimes on which the model critically depends. Using transgenic lines of zebrafish expressing her1 or her7 under heat-shock control, we confirm the regulatory relationships postulated by the model. From the timing of somite segmentation disturbances following a pulse of her7 misexpression, we deduce that although her7 continues to oscillate in the anterior half of the PSM, it governs the future somite segmentation behaviour of the cells only while they are in the posterior half. In general, the findings strongly support the mathematical model of how the somite clock works, but they do not exclude the possibility that other oscillator mechanisms may operate upstream from the her7/her1 oscillator or in parallel with it.
authors.affiliation: Vertebrate Development Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.
authors.forename: François
authors.initials: F
authors.lastname: Giudicelli
authors.forename: Ertuğrul M
authors.initials: EM
authors.lastname: Ozbudak
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Wright
authors.forename: Julian
authors.initials: J
authors.lastname: Lewis
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D001683:Biological Clocks / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018869:Heat-Shock Response / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D019170:Somites / Q000502:physiology*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C460099:HER7 protein, zebrafish; C064045:delta protein; C491619:her1 protein, zebrafish