DISTINCT AND OVERLAPPING EXPRESSION PATTERNS OF LIGANDS FOR EPH-RELATED RECEPTOR TYROSINE KINASES DURING MOUSE EMBRYOGENESIS

Recent studies have implicated Eph-related receptor tyrosine kinases a nd their membrane-bound ligands in restricting or stimulating the move ment of cells and axons. Members of these large families of receptors and ligands fall into two major binding specificity classes, in which the GPI-anchored subgroup of ligands can each bind to all members of a subgroup of receptors, whereas the transmembrane ligands interact wit h a distinct subgroup of receptors. Analysis of expression patterns is therefore important in order to understand which receptor-ligand inte ractions occur in vivo. We have cloned mouse orthologues of five membe rs of the ligand family and analysed in detail their developmental exp ression, in comparison with each other, and with the receptor specific ity class they can interact with. We find that B61, AL-1/RAGS, LERK4, and ELF-1, members of the GPI-anchored subgroup of ligands,have both d istinct and overlapping aspects to their expression in early mesoderm, somites, and branchial arches; in complex, dynamic patterns in the li mb; and in spatial domains and specific neurons in the CNS. Similarly, Elk-L is expressed in hindbrain segments, the roof plate, and floor p late, which overlaps with that of other transmembrane ligands, but has distinct expression in somites. The expression domains of ligands are complementary to those of the corresponding receptors in a number of tissues, including the midbrain, hindbrain, and differentiating limbs, consistent with potential roles in restricting cell movement. In addi tion, we find that there are some overlaps in expression of receptors and ligands, for Example in somites and the early limb, Taken together with previous studies showing that Eph related receptors also have di stinct but overlapping expression patterns, these data indicate that e ach ligand may have stage- and tissue-specific interactions with an in dividual member or multiple members of the receptor family. (C) 1996 A cademic Press, Inc.