A Notch feeling of somite segmentation and beyond.

Vertebrate segmentation is manifested during embryonic development as serially repeated units termed somites that give rise to vertebrae, ribs, skeletal muscle and dermis. Many theoretical models including the "clock and wavefront" model have been proposed. There is compelling genetic evidence showing that Notch-Delta signaling is indispensable for somitogenesis. Notch receptor and its target genes, Hairy/E(spl) homologues, are known to be crucial for the ticking of the segmentation clock. Through the work done in mouse, chick, Xenopus and zebrafish, an oscillator operated by cyclical transcriptional activation and delayed negative feedback regulation is emerging as the fundamental mechanism underlying the segmentation clock. Ubiquitin-dependent protein degradation and probably other posttranslational regulations are also required. Fgf8 and Wnt3a gradients are important in positioning somite boundaries and, probably, in coordinating tail growth and segmentation. The circadian clock is another biochemical oscillator, which, similar to the segmentation clock, is operated with a negative transcription-regulated feedback mechanism. While the circadian clock uses a more complicated network of pathways to achieve homeostasis, it appears that the segmentation clock exploits the Notch pathway to achieve both signal generation and synchronization. We also discuss mathematical modeling and future directions in the end.