Retinoic acid organizes the vagus motor topographic map via spatiotemporal regulation of Hgf/Met signaling

SUMMARY The topographic map, in which the positions of neuron cell bodies correspond with the positions of their synaptic targets, is a major organizational motif in the nervous system. To understand how topographic axon targeting is controlled during development, we examine the mechanism underlying topographic innervation of the pharyngeal arches by the vagus motor nerve in zebrafish. We reveal that Retinoic Acid organizes the topographic map by specifying anterior-posterior identity in post-mitotic vagus motor neurons. We then show that chemoattractant signaling between hepatocyte growth factor (Hgf) and the Met receptor is required for pharyngeal arch innervation by the vagus motor nerve. Finally, we find that Retinoic Acid controls the spatiotemporal dynamics of Hgf/Met signaling to coordinate axon targeting with the developmental progression of the pharyngeal arches and show that experimentally altering the timing of Hgf/Met signaling is sufficient to redirect axon targeting and disrupt the topographic map. These findings establish a new mechanism of topographic map development in which regulation of chemoattractant signaling in both space and time guides axon targeting.