Deciphering the somite segmentation clock: beyond mutants and morphants.
The regular pattern of somite segmentation depends on a clock, the somite segmentation clock, in the form of a gene expression oscillator, operating in the presomitic mesoderm (the PSM) at the tail end of the vertebrate embryo. Genetic screens and other approaches have identified a variety of genes, including components and targets of the Notch signalling pathway, that show transcriptional oscillations in this region and appear to be necessary for correct segmentation. Mathematical modelling shows that the oscillations could plausibly be generated by a simple mechanism of delayed negative feedback, based on autoinhibition of Notch target genes of the Hes/her family by their own protein products. To move beyond plausible models to an experimentally validated theory, however, it is necessary to measure the parameters on which the proposed model is based and to devise ways of probing the dynamics of the system by means of timed disturbances so as to compare with the model's predictions. Some progress is being made in these directions.
Lewis
Julian
J
Vertebrate Development Laboratory, Cancer Research UK London Research Institute, London, United Kingdom. julian.lewis@cancer.org.uk
Ozbudak
Ertugrul M
EM
D000818:Animals; D001683:Biological Clocks / Q000235:genetics / Q000502:physiology*; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D019170:Somites / Q000378:metabolism*
D018398:Homeodomain Proteins