Molecular regulation of trigeminal sensory ganglia development

三叉神经感觉神经节发育的分子调控

基本信息

批准号：
8217101
负责人：
Holger Knaut
金额：
$ 36.37万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-02-01 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8217101
关键词：
Accounting Address Adhesions Adhesives Affect Afferent Neurons Axon Behavior Binding Biological Models Brain CXCL12 gene Cadherins Cell Adhesion Cells Complex Development Disease Embryo Ensure Environment Esthesia Facial Pain Ganglia Genetic Goals Head Health Human Image Immigration Injury Label Ligands Light Mediating Membrane Modeling Molecular Nervous system structure Neural Crest Neuralgia Neurobiology Neurons Pain Pathway interactions Peptide Hydrolases Peripheral Phase Phenotype Population Process Property Proteins R-cadherin Recruitment Activity Recurrence Regulation Research Role Sensory Ganglia Signal Transduction Site Sorting - Cell Movement Source Stimulus Structure Temperature Testing Tissues Touch sensation Trigeminal Nerve Diseases Trigeminal System Vertebrates Work Zebrafish adhesion receptor afferent nerve base cadherin-6 chemokine chemokine receptor genetic manipulation in vivo insight malformation migration mutant nervous system development novel prevent promoter receptor receptor expression research study response segregation

项目摘要

DESCRIPTION (provided by applicant): The long-range goal of the proposed studies is to determine the cellular, genetic and molecular interactions that underlie trigeminal sensory ganglion development. The trigeminal sensory ganglion is the primary group of sensory nerves in the vertebrate head and mediates touch, temperature and pain sensations. It is formed from neural crest and placodal precursors that migrate to a shared assembly site. These two subpopulations segregate to different regions of the ganglion and differentiate into stimulus-specific neuronal subtypes. Malformations or injuries of the trigeminal sensory ganglion are associated with neuralgia, a recurrent facial pain condition. Despite its important role, very little is known about how the trigeminal sensory ganglion develops. This proposal focuses on the mechanisms by which trigeminal sensory neurons are recruited to the ganglion assembly site and how the two precursor populations sort to two distinct domains of the ganglion. Using zebrafish as a model, we will analyze neuron assembly and segregation by combining in vivo imaging of fluorescently labeled neuronal precursors with embryological and genetic manipulations. In Specific Aim 1, we will determine how chemokine signaling guides neurons to the assembly site. We will test the hypotheses that chemokine signaling is intrinsically long-range but becomes restricted to a short-range signal by the environment. In Specific Aim 2, we will determine how cell adhesion mediates sorting of neurons into different regions of the ganglion. We find that cell adhesion receptor expression divides the ganglion into different regions. We will test the hypothesis that neurons sort to different regions of the ganglion based on their adhesive properties. Lastly, we will ask how chemokine guidance and cell adhesion cooperate to organize the assembling ganglion. With these studies, we hope not only to provide insights into how neurons are organized into clusters, but also shed light onto the mechanisms underlying trigeminal neuropathies that can contribute to painful disease conditions afflicting humans. PUBLIC HEALTH RELEVANCE: Neurons in the nervous system are organized into layers and clusters. How this complex structure forms is unclear. We are using the trigeminal sensory ganglion in zebrafish as a model to address this question. In this proposal, we ask how chemokine signaling and cadherin cell adhesion receptors work together to assemble neurons into a cluster.

描述（由申请人提供）：拟议的研究的远距离目标是确定三叉神经节发育的基础的细胞，遗传和分子相互作用。三叉神经节神经节是脊椎动物头中的一组感觉神经，并介导触摸，温度和疼痛感觉。它是由迁移到共享组装位点的神经rest和placodal前体形成的。这两个亚群将神经节的不同区域隔离，并分化为刺激特异性的神经元亚型。三叉神经节神经节的畸形或伤害与神经痛有关，神经痛是一种反复出现的面部疼痛状况。尽管它具有重要的作用，但对三叉神经节神经节的发展知之甚少。该提议着重于将三叉神经元神经元募集到神经节组件部位的机制，以及两个前体种群如何将其分类到神经节的两个不同领域。使用斑马鱼作为模型，我们将通过结合荧光标记的神经元前体的体内成像与胚胎和遗传操纵的体内成像来分析神经元组装和隔离。在特定的目标1中，我们将确定趋化因子信号如何将神经元引导到组装位点。我们将测试趋化因子信号传导本质上是远距离的假设，但限于环境的短距离信号。在特定的目标2中，我们将确定细胞粘附如何介导神经元的分类为神经节的不同区域。我们发现细胞粘附受体表达将神经节分为不同区域。我们将检验以下假设：神经元基于神经节的粘附特性对不同区域进行分类。最后，我们将询问趋化因子引导和细胞粘附如何合作组织组装神经节。通过这些研究，我们不仅希望提供有关神经元如何组织成簇的见解，而且还希望对三叉神经病的机制进行启示，这些机制可能导致痛苦的疾病疾病困扰人类。公共卫生相关性：神经系统中的神经元被组织成层和簇。这种复杂结构的形式尚不清楚。我们将斑马鱼中的三叉神经节神经节用作解决这个问题的模型。在此提案中，我们询问趋化因子信号传导和钙粘蛋白细胞粘附受体如何共同起作用，将神经元组装成簇。