During development, families of ligands and receptors control concurrent processes, but how do cells discriminate between closely related signals? To find out, Erez Raz and co-workers have been studying chemokine signalling during primordial germ cell (PGC) migration in zebrafish embryos (see p. ). In vertebrates, the chemokine Cxcl12, which binds the Cxcr4 receptor, guides PGC migration. Zebrafish express two Cxcl12 paralogues and two Cxcr4 receptors. The researchers report that, although PGCs can respond to both Cxcl12 ligands, only Cxcl12a, which exhibits a higher affinity than Cxcl12b for one of the receptors (Cxcr4b), guides the cells. Moreover, a single amino acid exchange switches the relative affinity of the Cxcl12 ligands for the duplicated Cxcr4 receptors, allowing each chemokine to elicit a distinct effect. The researchers suggest that the subfunctionalisation of the cxcl12 genes that followed their duplication occurred through alterations in their expression patterns and in the specificity of receptor binding. Subfunctionalisation of this sort, they suggest, could enable chemokines and other receptor-ligand families to control concurrent developmental processes.
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