The assembly of the peripheral nervous system occurs in a precise order: motor efferent axons (MEs) emerge first, followed by somatosensory afferent axons (SAs), and then by sympathetic efferent axons (SEs). While this order is clearly defined, it is not clear whether the pioneering axons provide instructive cues for the trailing axons to follow, and thus whether the network represents a true hierarchy. In this issue (p. ), Till Marquardt and colleagues take an evolutionary approach to address this issue, and find that peripheral nerve assembly is governed by a stringent hierarchy of axon-dependent interactions. Using elegant in vivo genetic analyses to manipulate sensory and motor axons networks in three different vertebrate organisms – fish, chick and mouse – the authors show that MEs act as pioneer axons, laying down tracks that are followed by SAs, which in turn act as pioneers for SEs. The authors argue that this hierarchy mirrors the phylogenetic emergence of peripheral nerve types during vertebrate evolution.
