Wednesday 29 October 2003
A transcriptional oscillator
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.
vertebral segmentation anomalies
Giudicelli F, Lewis J. The vertebrate segmentation clock. Curr Opin Genet Dev. 2004 Aug;14(4):407-14. PMID: #15261657#
Saga Y, Takeda H. The making of the somite: molecular events in vertebrate segmentation. Nat Rev Genet. 2001 Nov;2(11):835-45. PMID: #11715039#