Specification and segmentation of the paraxial mesoderm

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Abstract
Somite formation in the mouse embryo begins with the recruitment of mesenchymal cells into the paraxial mesoderm. Cells destined for the paraxial mesoderm are recruited from a progenitor population found first in the embryonic ectoderm and later in the primitive streak and the tail bud. Experimental evidence suggests that the allocation of precursor cells to different mesodermal lineages may be related to the site at which the cells ingress through the primitive streak. An increasing number of genes, such as those encoding growth factor and transcription factors, are now known to be expressed in the primitive streak. It is not known whether the specification of mesodermal cell fate has any relationship with the activity of genes that are expressed in the restricted cell populations of the primitive streak. Somitomeres, which are spherical clusters of mesenchymal cells in the presomitic mesoderm, presage the segmentation of somites in the paraxial mesoderm. The somitomeric organization denotes a pre-pattern of segmentation that defines the physical boundary and the bilateral symmetry of the mesodermal segments in the body axis. The establishment of new somitomeres seems to require the interaction of a resident cell population in the presomitic mesoderm and the incoming primitive streak cells. Cell mixing, which occurs in the somitomeres prior to somite segmentation, poses problems in understanding the developmental role of the somitomere and the real significance of the partitioning of the node-derived and primitive streak-derived cells in the mesodermal segments. In the presomitic mesoderm, the expression of some genes that encode transcription factors, growth factors or tyrosine kinase receptor, and the localization of certain cell adhesion molecules are closely associated with distinct morphogenetic events, such as cell clustering in the presomitic mesoderm and the formation of epithelial somites. There is, however, very little direct relationship between the spatial pattern of gene expression and the somitomeric organization in the presomitic mesoderm. Results of somite transplantation experiments suggest that both the segmental address and the morphogenetic characteristics of the somite may be determined during somite segmentation. Regional identity of the paraxial mesodermal segment is conferred by the expression of a combination of Hox genes in the sclerotome and probably other lineage-specific genes that are subject to imprinting. Superimposed on the global metameric pattern, two orthogonal polarities of cell differentiation are endowed in each mesodermal segment. The rostro-caudal polarity is established prior to somite segmentation. This polarity is later manifested by the subdivision of the sclerotome and the alliance of the neural crest cells and motor axons with the rostral half-somite. The dorso-ventral polarity is installed after somite segmentation, probably by an inductive mechanism similar to that which specifies the dorso-ventral pattern of neuronal differentiation in the neural tube. The segmental pattern of the paraxial mesoderm has been found to exert a direct impact not only on the morphogenesis of the vertebral column, but also on the segmental organization of the lateral mesoderm, the peripheral nervous system and the craniofacial structures.