Topographic mapping by cranial motor neurons

颅运动神经元的地形图

• 批准号: 10610122
• 负责人: Cecilia B Moens
• 金额: $ 27.21万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10610122
• 关键词: Topographic; mapping; cranial; motor; neurons

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.

摘要 地形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表示在目标场中。地形图 是脊椎动物神经系统组织中的常见主题，对我们的能力至关重要 感知世界，准确回应世界，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。 到大脑的视觉中枢和脊髓中的运动神经元的投射到特定的 以肢体肌肉为目标。脊椎动物后脑中的颅运动神经元表现出一种拓扑学-- 与头周部咽弓派生的肌肉的图形关系 支配，因此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活体成像和移植的透明斑马鱼模型 他们发现，在迷走神经(X脑神经)运动前体内可以检测到地形图。 投射到3天胚胎的后咽弓，发现了两个平行的 控制其形成的LEL策略：HOX调控的分子机制和一种新的TEM-2 迷走神经轴突起始的时间被调节为与序列相匹配的临时性机制 咽弓靶点的发展。我们将此称为“时间匹配”模型，称为Distin-- 从地形图的经典空间匹配(化学亲和力)模型中推测出来。这个 该提案的总体目标是发现HOX调节和时间匹配机制是如何- 反常现象共同规范着地形图绘制。我们将通过以下方式确定其分子机制 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 目标1中咽弓发育的时机。我们将确定引导途径，即 由目标2中的hox5基因调控。最后，我们将确定这两种机制如何协调。 在目标3中由空间线索直接调控。最终我们的目标是阐明新机制 地形图测绘及其在发展过程中的调整和整合。