The expression and regulation of chick EphA7 suggests roles in limb patterning and innervation

Eph receptors and their ligands, the ephrins, have been implicated in early patterning and axon guidance in vertebrate embryos. Members of these famil ies play pivotal roles in the formation of topographic maps in the central nervous system, the formation of brain commissures, and in the guidance of neural crest cells and motor axons through the anterior half of the somites , Here, we report a highly dynamic expression pattern of the chick EphA7 ge ne in the developing limb. Expression is detected in discrete domains of th e dorsal mesenchyme from 3 days of incubation. The expressing cells are adj acent to the routes where axons grow to innervate the limb at several key p oints: the region of plexus formation, the bifurcation between dorsal and v entral fascicles, and the pathway followed by axons innervating the dorsal muscle mass. These results suggested a role for EphA7 in cell-cell contact- mediated signalling in dorsal limb patterning and/or axon guidance. We carr ied out experimental manipulations in the chick embryo wing bud to alter th e dorsoventral patterning of the limb. The analyses of EphA7 expression and innervation in the operated wings indicate that a signal emanating from th e dorsal ectoderm regulates EphA7 in such a way that, in its absence, the w ing bud lacks EphA7 expression and shows innervation defects at the regions where the gene was downregulated. EphA7 downregulation in the dorsal mesen chyme after dorsal ectoderm removal is more rapid than that of Lmx-1, the g ene known to mediate dorsalisation in response to the ectodermal signal, Th ese results add a new gene to the dorsalisation signalling pathway in the l imb. Moreover, they implicate the Eph receptor family in the patterning and innervation of the developing limb, extending its role in axon pathfinding to the distal periphery.