Expression of EphA4, ephrin-A2 and ephrin-A5 during axon outgrowth to the hindlimb indicates potential roles in pathfinding

During neural development, spinal motor axons extend in a precise manner fr om the ventral portion of the developing spinal cord to innervate muscle ta rgets in the limb. Although classical studies in avians have characterized the cellular interactions that influence motor axon pathfinding to the limb , less is known about the molecular mechanisms that mediate this developmen tal event. Here, we examine the spatiotemporal distributions of the EphA4 r eceptor tyrosine kinase (RTK) and its cognate ligands, ephrin-A2 and ephrin -A5, on motor neurons, their axons and their pathways to the avian hindlimb to determine whether these molecules may influence axonal projections. The expression patterns of EphA4, ephrin-A2 and ephrin-A5 mRNAs and proteins a re highly complex and appear to exhibit some overlap during motor axon outg rowth and pathfinding to the hindlimb, reminiscent of the co-expression of Eph RTKs and ephrins in the retinotectal system. EphA4, similar to the carb ohydrate moiety polysialic acid, strikingly marks the main dorsal, but not ventral, nerve trunk after axon sorting at the limb plexus region. Our resu lts suggest that EphA4 RTK and its ligands may influence axon fasciculation and the sorting of axons at the limb plexus, contributing to the correct d orsoventral organization of nerve branches in the hindlimb, Copyright (C) 2 000 S. Karger AG, Basel.