Topographic neural maps are ordered connections between the brain and the periphery in which spatial coordinates in the projecting field are represented in the target field. Topographic maps are a common motif in vertebrate nervous system organization and are critical for our ability to perceive the world and accurately respond to it, so their development is of fundamental interest to neurobiology. Examples of topographic maps are in the ordered projections of retinal neurons to visual centers in the brain and in the projections motor neurons in the spinal cord to specific target muscles in the limb. Cranial motor neurons in the vertebrate hindbrain exhibit a topo- graphic relationship with the pharyngeal arch-derived muscles in the head periphery that they innervate, whereby more anterior neurons innervate more anterior pharyngeal arches. Using the transparent zebrafish model for live imaging and transplantation of single motor neurons, we have found that a topographic map is detectable within the vagus (cranial nerve X) motor pro- jections to the posterior pharyngeal arches in the 3-day embryo, and have discovered two paral- lel strategies that govern its formation: a Hox-regulated molecular mechanism and a novel tem- poral mechanism in which timing of vagus axon initiation is regulated to match the sequential development of the pharyngeal arch targets. We call this a ?temporal matching? model as distin- guished from classical spatial matching (chemoaffinity) models of topographic mapping. The overall aim of this proposal is to discover how the Hox-regulated and temporal matching mech- anisms together regulate topographic mapping. We will identify the molecular mechanism by which timing of vagus axon initiation is spatially regulated in vivo and how it is matched to the timing of pharyngeal arch development in Aim 1. We will identify the guidance pathway that is regulated by hox5 genes in Aim 2. Finally, we will determine how the two mechanisms are coor- dinately regulated by spatial cues in Aim 3. Ultimately our goal is to elucidate novel mechanisms of topographic mapping, their regulation and integration during development.
RESEARCH & RELATED Other Project Information 8. Project Narrative We propose to study a fundamental problem in brain development: how neurons project their axons to a target field such that the spatial relationships amongst the neuron cell bodies are reflected in the spatial arrangement of their targets; a process called topographic mapping. The neuronal projection whose topographic map we study is that of the vagus efferent neurons in the brainstem, which control speech and swallowing as well as autonomic functions like heartbeat, breathing and digestion. There is growing interest in the vagus nerve as a target for treating a variety of cardiac and gastrointestinal disorders, so it is important to understand the spatial relationships between vagus neurons and their targets.
