The vertebrate segmentation clock.
In vertebrate embryos, somite segmentation is controlled by a molecular clock, in the form of a transcriptional oscillator that operates in the presomitic mesoderm. Most of the genes implicated in the oscillator belong to the Notch pathway; a recently discovered exception is the Wnt pathway gene Axin2. Experiments have revealed several negative feedback loops that might generate oscillations, leading to at least four different theories. The simplest of these is based on direct autoinhibition of certain members of the hairy/E(spl) family of Notch target genes--Hes7 in the mouse, and her1 and her7 in the zebrafish. A mathematical account of this mechanism explains some surprising observations and suggests that the period of oscillation is chiefly determined by the transcriptional and translational delays--the times required to make a molecule of the mRNA and a molecule of the protein.
Giudicelli
François
F
Vertebrate Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. francois.giudicelli@cancer.org.uk
Lewis
Julian
J
D000818:Animals; D060466:Axin Protein; D051792:Basic Helix-Loop-Helix Proteins; D001683:Biological Clocks / Q000502:physiology*; D019521:Body Patterning / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D047108:Embryonic Development / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D051880:Receptors, Notch; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014714:Vertebrates / Q000196:embryology*; D051153:Wnt Proteins
D060466:Axin Protein; D051792:Basic Helix-Loop-Helix Proteins; D003598:Cytoskeletal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D014157:Transcription Factors; D051153:Wnt Proteins; C111729:Axin2 protein, mouse; C430525:Hes7 protein, mouse