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 F ，Lewis J 《CURRENT OPINION IN GENETICS & DEVELOPMENT》

Completing the set of h/E(spl) cyclic genes in zebrafish: her12 and her15 reveal novel modes of expression and contribute to the segmentation clock.

Shankaran SS ，Sieger D ，Schröter C ，Czepe C ，Pauly MC ，Laplante MA ，Becker TS ，Oates AC ，Gajewski M ... -  《DEVELOPMENTAL BIOLOGY》

Noise-resistant and synchronized oscillation of the segmentation clock.

Horikawa K ，Ishimatsu K ，Yoshimoto E ，Kondo S ，Takeda H ... -  《-》

Mouse Nkd1, a Wnt antagonist, exhibits oscillatory gene expression in the PSM under the control of Notch signaling.

Ishikawa A ，Kitajima S ，Takahashi Y ，Kokubo H ，Kanno J ，Inoue T ，Saga Y ... -  《MECHANISMS OF DEVELOPMENT》

Oscillator mechanism of Notch pathway in the segmentation clock.

Somites are formed by periodic segmentation of the presomitic mesoderm (PSM). This periodic event is controlled by the segmentation clock, where Notch signaling plays an essential role. The basic helix-loop-helix factor Hes7, a Notch effector, is cyclically expressed by negative feedback and regulates cyclic expression of Lunatic fringe (Lfng), a Notch modulator. Lfng then seems to periodically inhibit Notch, leading to oscillation in Notch activity. It is thought that these coupled negative feedback loops by Hes7 and Lfng are important for sustained and synchronized oscillations in the PSM. Of interest, another Notch effector, Hes1, is cyclically expressed by many cell types such as neuroblasts, suggesting that this clock is widely distributed and regulates many biological events. This review summarizes the recent finding about roles and mechanism of Notch signaling in the segmentation clock and discusses the significance of Hes1 oscillation in non-PSM cells.

Kageyama R ，Masamizu Y ，Niwa Y 《DEVELOPMENTAL DYNAMICS》