Topographic mapping by cranial motor neurons

颅运动神经元的地形图

基本信息

批准号：
9791356
负责人：
Cecilia B Moens
金额：
$ 48.57万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
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/9791356
关键词：
Anterior Axon Brain Brain Stem Branchial arch structure Breathing Cells Cephalic Cranial Nerves Cues Deglutition Development Digestion Efferent Neurons Embryo Environment Exhibits Gastrointestinal Diseases Gene Expression Genes Genetic Goals Head Heart Diseases Heart Rate Homeobox Genes Human Ice Image Larynx Ligands Limb structure Maps Modeling Molecular Motor Motor Neurons Muscle Nervous system structure Neuraxis Neurobiology Neurons Pathway interactions Pharyngeal structure Process Regulation Retina Retinal Ganglion Cells Role Speech Spinal Cord Structure System Tectum Mesencephali Time To specify Translating Transplantation Vagus nerve structure Viscera Visual Work Zebrafish axon guidance axonal guidance experimental study hindbrain in vivo in vivo evaluation interest nerve supply neuron development novel preservation receptor expression relating to nervous system retinal neuron retinotopic spatial relationship superior colliculus Corpora quadrigemina

项目摘要

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.

概括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。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，发展才是根本利益神经生物学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脊椎动物后脑中的目标肌肉表现出拓扑结构。与头部周边咽弓衍生肌肉的图形关系神经支配，因此更多的前神经元支配更多的前咽弓。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我们将其称为“时间匹配”模型，以区别于咽弓目标。源自地形测绘的经典空间匹配（化学亲和力）模型。该提案的总体目标是发现 Hox 调节和时间匹配机制如何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。