Analysis of EphA4 in the lesser spotted catshark identifies a primitive gnathostome expression pattern and reveals co-option during evolution of shark-specific morphology

The Eph family is the largest known group of structurally related receptor tyrosine kinases (RTKs). Each Eph receptor has a specific Ephrin ligand, and these function to define spatial boundaries during development. Analyses of EphA4 in mouse, chick, frog and zebrafish embryos have implicated this gene in a number of developmental processes, including maintenance of segmental boundaries, axon guidance, limb development, neural crest migration and patterning of the ear. In order to determine which components of EphA4 function may be primitive for gnathostomes, we cloned EphA4 from the lesser spotted catshark ( Scyliorhinus canicula) and examined its expression pattern during shark embryonic development. Consistent with the patterns reported for bony fish and tetrapods, we observed segmental expression of EphA4 in the developing hindbrain and later in the pharyngeal arches of shark embryos. EphA4 was also detected during sensory organogenesis, in the developing ear, eye, nasal pits and lateral line. A dynamic pattern of EphA4expression occurs during shark fin development, suggesting an early role in outgrowth and patterning of the fin buds and a later role in tissue differentiation. We also observed several novel domains of EphA4expression that have not been reported in other vertebrates, including external gill buds, dermal denticles, median fins and claspers. While some of these domains may reflect co-option of EphA4expression to novel sites for development of shark-specific characters, others are more likely to be ancestral patterns of expression that were lost in other vertebrate lineages.