Figure 1. A 2-day-old chicken embryo diagrammatically shows sequential differentiation of the somitic mesoderm. Paraxial mesoderm is generated in the caudal-most region of the body through the gastrulation process. The more anteriorly located, the more mature the cells become. Segmentation takes place in an anterior to posterior order and produces a pair of somites one at a time. Segmentation is accompanied with drastic changes in the state of cells, including cell shape, constitution in a three-dimensional architecture, and cell differentiation. Soon after segmentation is completed, dermomyotome and sclerotome emerge and subsequently the myotome differentiates between them.

Figure 2. An outline of vertebrate segmentation. (a) The mode of segmentation is different between vertebrates and flies as seen in anology with the simultaneous and multiple cuts made by an egg slicer (flies), contrasted with the serial single slicing of a loaf of bread (vertebrates). (b) Segmentation processes are divided into three distinct steps. Molecular clock determines the rhythm of oscillation in the posterior PSM. This is resolved into a gene expression activity that shows a discrete segmental pattern at the presumptive boundary site. By following the segmental gene activities, cells at the boundary site manifest a dynamic change in shape, resulting in a separation of tissues to make a somite.

Figure 3. The segmenter acts as a ‘knife’ carving the somite. The segmenter was found as an activity that could induce an ectopic boundary when placed into a nonsegmentation site. The segmenter resides in specified cells that are posteriorly located to the presumptive boundary. Photos show a chicken embryo that received the segmenter in a nonsegmentation site. The treated side (right side of the body) has two miniature somites with an ectopic boundary that was caused by the graft. Brown cells are segmenter-producing cells transplanted from a donor embryo (quail). Modified from Sato et al. (2002).

Figure 4. Molecular clock counting the segmentation rhythm. L-fringe and c-hairy 1 (Notch-related molecules) are expressed in the way in which their expression forms waves from posterior to anterior in the PSM. PSM cells do not move, indicating that the cells oscillate expression of these genes once every cycle. The position where the expression stops is a future boundary site (indicated by scissors).

Figure 5. Cellular and tissue communications are important for the production of distinct compartments within a somite. A most recently formed somite is not determined along the dorsoventral and mediolateral axes. It then starts to receive a variety of signals emanating from neighbouring tissues and subsequently produces dermomyotome and sclerotome in its dorsal and ventral regions of the somite, respectively. For the sclerotome differentiation, the notochordal signals are crucial and they are mediated by Shh and Noggin. The surface ectoderm and dorsal neural tube send many kinds of secretory proteins to the dermomyotome. Meanwhile, the somite becomes polarized along the mediolateral axis by a condensation gradient of BMP4.

Figure 6. Somites impose the segmented pattern on neighbouring tissues. Spinal nerves normally favour the anterior half of each somite when they find their way to extend (left). When a somite is experimentally inverted along the antero-posterior axis, the spinal nerves extend their axons in the posterior half, which was originally of the anterior character. This experiment showed that the somitic segmentation has the initiative to instruct the periodic pattern of other tissues.

Figure 7. Identities of somites and Hox genes. Vertebrates have four clusters of Hox genes (Hox A–D) in different chromosomes. There is a colinearity between alignment of the genes on a cluster and spatial pattern of expression in the body; genes located at 3¢ end of cluster are expressed anteriorly whereas ones at 5¢ end are active in posterior regions of the body. This figure also shows a tight correlation between spatial patterns of Hox expression and morphological phenotypes. Another remarkable feature is that although the number of the somites in each morphologically distinct regions, for example the cervical, is different between chickens and mice, the A–P level of the interface between Hox 6-on and -off regions coincides with the position of fore limbs. Modified from Burke (2000).