Topographic mapping by cranial motor neurons

摘要 地形神经图是大脑和外周之间的有序连接，其中 投影场中的空间坐标在目标场中表示。地形图 是脊椎动物神经系统组织中的常见基序，对于我们的能力至关重要 感知世界并准确应对世界，发展才是根本利益 到神经生物学。地形图的例子是视网膜神经元的有序投影 大脑中的视觉中心和脊髓中的运动神经元的投射到特定的 目标肢体肌肉。脊椎动物后脑中的颅运动神经元表现出拓扑结构 与头部周边咽弓衍生肌肉的图形关系 神经支配，即更多的前神经元支配更多的前咽弓。使用 用于单个运动神经元实时成像和移植的透明斑马鱼模型，我们 发现在迷走神经（X 脑神经）运动亲内可以检测到地形图 注射到 3 天胚胎的后咽弓，并发现了两个平行的 控制其形成的lel策略：Hox调节的分子机制和新的温度 调节迷走神经轴突起始时间以匹配顺序的口腔机制 咽弓目标的发育。我们称其为“时间匹配”模型 源自地形测绘的经典空间匹配（化学亲和力）模型。的 该提案的总体目标是发现 Hox 调节和时间匹配机制如何 动物共同调节地形测绘。我们将通过以下方式确定分子机制 迷走神经轴突起始的时间在体内受到空间调节以及它如何与 目标 1 中咽弓发育的时间。我们将确定指导路径 目标2中受hox5基因调节。最后，我们将确定这两种机制如何协调 目标 3 中的空间线索直接调节。最终我们的目标是阐明新机制 地形测绘及其在开发过程中的调节和整合。

SUMMARY 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.