Axon-axon interactions in neuronal circuit assembly: lessons from olfactory map formation

During the development of the nervous system, neurons often connect axons and dendrites over long distances, which are navigated by chemical cues. During the past few decades, studies on axon guidance have focused on chemical cues provided by the axonal target or intermediate target. However, recent studies have shed light on the roles and mechanisms underlying axonaxon interactions during neuronal circuit assembly. The roles of axonaxon interactions are best exemplified in recent studies on olfactory map formation in vertebrates. Pioneerfollower interaction is essential for the axonal pathfinding process. Pre-target axon sorting establishes the anteriorposterior map order. The temporal order of axonal projection is converted to dorsalventral topography with the aid of secreted molecules provided by early-arriving axons. An activity-dependent process to form a discrete map also depends on axon sorting. Thus, an emerging principle of olfactory map formation is the self-organisation of axons rather than the lock and key matching between axons and targets. In this review, we discuss how axonaxon interactions contribute to neuronal circuit assembly.