We report that the many Eph-related receptor tyrosine kinases, and their numerous membrane-bound ligands, can each be grouped into only two major specificity subclasses. Receptors in a given subclass bind most members of a corresponding ligand subclass. The physiological relevance of these groupings is suggested by viewing the collective distributions of all members of a subclass. These composite distributions, in contrast with less informative patterns seen with individual members of the family, reveal that the developing embryo is subdivided into domains defined by reciprocal and apparently mutually exclusive expression of a receptor subclass and its corresponding ligands. Receptors seem to encounter their ligands only at the interface between these domains. This reciprocal compartmentalization implicates the Eph family in the formation of spatial boundaries that may help to organize the developing body plan.

Slug, a vertebrate gene encoding a zinc finger protein of the Snail family, is expressed in the neural crest and in mesodermal cells emigrating from the primitive streak. Early chick embryos were incubated with antisense oligonucleotides to chick Slug. These oligonucleotides specifically inhibit the normal change in cell behavior that occurs at the two sites in the emerging body plan in which the gene is expressed. This change, which is the transition from epithelial to mesenchymal character, occurs at the formation of mesoderm during gastrulation and on emigration of the neutral crest from the neural tube.

Formation of mesoderm is a crucial event in vertebrate development, establishing many of the important features of the body. Recent studies have implicated molecules that are similar to growth factors in mesoderm formation in Xenopus, but other gene products involved in this process have yet to be identified. Genetic evidence indicates that in the mouse the T gene (Brachyury) has a role in the formation and organization of mesoderm. Mice homozygous for mutant alleles of the T gene do not generate enough mesoderm, and show severe disruption in morphogenesis of mesoderm-derived structures, in particular the notochord. The cloning of the T gene has now allowed us to examine its expression pattern. We report that T-gene expression occurs in both early stage mesoderm and its epithelial progenitor, and then becomes restricted to the notochord. This expression pattern correlates with the tissues affected in the T-gene mutant, and indicates that the T gene has a direct role in the early events of mesoderm formation and in the morphogenesis of the notochord.

No abstract

The control of cell movement during development is essential for forming and stabilizing the spatial organization of tissues and cell types. During initial steps of tissue patterning, distinct regional domains or cell types arise at appropriate locations, and the movement of cells is constrained in order to maintain spatial relationships during growth. In other situations, the guidance of migrating cells or neuronal growth cones to specific destinations underlies the establishment or remodeling of a pattern. Eph receptor tyrosine kinases and their ephrin ligands are key players in controlling these cell movements in many tissues and at multiple stages of patterning.