Harvard Medical School, Boston | United States
The body axis of vertebrates is composed of a serial repetition of similar anatomical modules, termed segments or metameres. This particular mode of organization is especially conspicuous at the level of the periodic arrangement of vertebrae in the spine. The segmental pattern is established during embryogenesis when the somites, the embryonic segments of vertebrates, are rhythmically produced from the paraxial mesoderm. This process involves the segmentation clock, a traveling oscillator that interacts with a maturation wave called the wavefront to produce the periodic series of somites. This clock drives the dynamic expression of cyclic genes in the presomitic mesoderm and requires Notch and Wnt signaling. Microarray studies of the mouse presomitic mesoderm transcriptome reveal that the segmentation clock drives the periodic expression of a large network of cyclic genes involved in cell signaling. In humans, mutations in the genes associated to the function of this oscillator result in abnormal segmentation of the vertebral column such as those seen in congenital scoliosis. Whereas the segmentation clock is thought to set the pace of vertebrate segmentation, the translation of this pulsation into the reiterated arrangement of segment boundaries along the AP axis involves dynamic gradients of FGF and Wnt signaling. The FGF signaling gradient is established based on an unusual mechanism involving mRNA decay which provides an efficient means to couple the spatio-temporal activation of segmentation to the posterior elongation of the embryo. Finally, the subsequent regional differentiation of the precursors of the vertebrae is controlled by Hox genes, whose collinear expression controls both gastrulation of somite precursors and their subsequent patterning into anatomical domains. Therefore somite development provides an outstanding paradigm to study patterning and differentiation in vertebrate embryos and a conceptual framework to explain human spine malformations, such as scoliosis.
Keywords: Developmental biology / segmentation / somitogenesis / morphogenesis / patterning / signaling