Previous and current research
Segmentation, or the use of serially repeated anatomical units is a fundamental feature of the body plan of many animal phyla. The segmented architecture of the vertebrate embryo and its relationship to the segmented structures of the adult has been appreciated for centuries, but the mechanisms establishing this spatial pattern during embryogenesis are only just being deciphered. In zebrafish embryos, as in all vertebrates, the reiterated skeleton and muscles of the adult are formed from the embryonic paraxial mesoderm. Beginning in the anterior of the embryo, this tissue progressively segments through the serial formation of epithelialized blocks of cells called somites from the more posterior, mesenchymal pre-somitic mesoderm (PSM). A remarkable insight into the control of vertebrate segmentation has come from recent findings of dynamic, wave-like gene expression patterns sweeping through the PSM prior to somite formation. These expression domains travel anteriorly through the PSM from the tailbud, then arrest at a location that predicts the site of a future somite boundary. These cyclic expression patterns are believed to represent the activity of coordinated biochemical oscillators in the cells of the PSM, and this oscillator has been dubbed the segmentation clock. Despite recent progress indicating that genes and proteins of the Delta/Notch signal transduction system are critical components of its structure, we do not yet understand the molecular mechanism driving its oscillation, the details of the oscillation dynamics, or the mechanism coordinating the oscillation phases of neighboring cells. Furthermore, we still do not understand how the output of this clock communicates timing information to the PSM cells that will respond morphologically by forming the regularly spaced boundaries of somites.

By understanding the mechanism of the oscillator and how it generates boundaries in a tissue with changing geometry, we may learn about how the rate of sequential segment formation is coordinated with overall embryonic body growth. Indeed, how patterning and growth are coordinated during embryogenesis remains a central, and largely unexplored issue in biology. Further, from an evolutionary perspective, we may learn about the genetics of segment number change. Since changes in oscillator period would alter segment size, and therefore segment number, variation in oscillator structure may be a mechanism underlying the tremendous change in vertebral number seen with the phylum vertebrata e.g. ten segments in some frogs versus hundreds in snakes.

Finally, the discovery of a new kind of biochemical oscillator is cause for great scientific excitement. All other biological oscillators, such as the circadian clock, appear to regulate the timing of biological phenomena, whereas the segmentation oscillator is used by the animal to measure distance. How does the embryo interpret the distance? Is the oscillator used in other patterning tasks? Is it also used for timing? What differences and similarities exist between the mechanisms of circadian and segmentation oscillators? We may expect that the comparison of the logical structure of these oscillators will reveal generalized principles of the organization and stability of biochemical networks that will guide efforts to interpret genome structure and expression.