Extensive molecular differences between anterior- and posterior-half-sclerotomes underlie somite polarity and spinal nerve segmentation

Several hundred genes are differentially-expressed between the two sclerotome halves, showing that a marked degree of molecular heterogeneity underpins the development of somite polarity.We have identified a set of genes that warrant further investigation as regulators of somite polarity and vertebral morphogenesis, as well as repellents of spinal axon growth. Moreover the results indicate that, unlike the posterior half-sclerotome, the central region of the anterior-half-sclerotome does not contribute bone and cartilage to the vertebral column, being associated instead with the development of the segmented spinal nerves.The subdivision of embryonic tissues into serial repeat-units, or segments, is a fundamental patterning process in early vertebrate development, and is most prominent in the formation of the mesodermal somites. Somites arise as paired epithelial spheres that bud off from the undifferentiated paraxial mesoderm (presomite mesoderm, PSM) flanking the notochord, and subsequently give rise to several tissues including the segmented axial skeleton and epaxial musculature of the adult organism [1,2].The formation and development of somites involves the superposition of two orthogonal patterning systems acting within the paraxial mesoderm. The first operates along the anterior-posterior (A-P) axis and is intrinsic to the paraxial mesoderm, resulting in individuation of the somites and their concomitant polarization into anterior and posterior halves (Figure 1). Somite formation is dependent on a molecular 'clock' within the PSM that generates periodic expression of genes including the notch, wnt and fibroblast growth factor (FGF) signalling pathways [3-5]. These cyclical gene expression patterns are superimposed on a regressing, longitudinal gradient of FGF expression along the A-P axis that results in the co-ordinated maturation of groups of PSM cells into each successive somite. Somite polarity is determined within the anterior PSM by a complex feedback m