Topographic mapping by cranial motor neurons

总结 地形神经地图是大脑和周边之间的有序连接， 投影场中的空间坐标被表示在目标场中。地形图 是脊椎动物神经系统组织中的一个常见基序，对我们的能力至关重要， 感知世界并准确应对，因此他们的发展是根本利益所在 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投射到特定的 瞄准肢体的肌肉脊椎动物后脑中的颅运动神经元表现出拓扑结构， 与咽弓衍生肌肉在头部周边的图形关系， 神经支配，从而更多的前神经元支配更多的前咽弓。使用 透明的斑马鱼模型，用于活体成像和单个运动神经元移植，我们 已经发现，在迷走神经（颅神经X）运动原中可以检测到地形图， 在3天的胚胎中，咽后弓的喷射，并发现了两个平行的， 控制其形成的lel策略：一种Hox调节的分子机制和一种新的TEM- 迷走神经轴突起始的时间被调节以匹配顺序的 咽弓目标的发展。我们称之为“时间匹配”模型， 从经典的空间匹配（化学亲和性）模型的地形图。的 这项建议的总体目标是发现如何Hox调节和时间匹配机制， 各民族共同管理地形测绘。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是空间调节的，以及它是如何与神经元相匹配的。 目标1中咽弓发育的时间。我们将确定指导途径， 在Aim 2中受hox 5基因调控。最后，我们将确定这两种机制是如何协调的- 在目标3中受空间线索的直接调节。最终我们的目标是阐明新的机制 地形图的绘制，它们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.