Spatial and temporal mechanisms of vagus motor neuron topographic map development

Abstract

Many networks throughout the nervous system are organized into topographic maps, where the positions of neuron cell bodies in the projecting field correspond with the positions of their axons in the target field. Previous studies of topographic map development show evidence for spatial patterning mechanisms, in which gene expression patterns in the projecting and target fields determine axon targeting in a manner that depends on the precise positions of the cell bodies. Here, we describe a novel mechanism of topographic map formation that depends on the timing of axon outgrowth, and that is overlaid on spatial patterning mechanisms. We focus on the vagus motor neurons, which are topographically arranged in both mammals and fish. We show that cell position along the anterior-posterior axis of hindbrain rhombomere 8 determines expression of hox5 genes, which are expressed in posterior vagus motor neurons. Using live-imaging techniques in zebrafish embryos, we additionally reveal a difference in time of axon formation between anterior versus posterior motor neurons that is independent of neuron birth time. We show that hox5 expression directs topographic mapping without affecting time of axon outgrowth, and that time of axon outgrowth directs topographic mapping without affecting hox5 expression. The vagus motor neuron topographic map is therefore determined by two mechanisms that are acting in parallel: a hox5-dependent spatial mechanism akin to classic mechanisms of topographic map formation, and a novel axon outgrowth-dependent temporal mechanism in which time of axon formation is differentially regulated to direct axon targeting.