MOLECULAR GENETICS OF SENSORY GANGLIA DEVELOPMENT

感觉神经节发育的分子遗传学

• 批准号: 6925444
• 负责人: ALEXANDER F SCHIER
• 金额: $ 30.34万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6925444
• 关键词: alternatives to animals in research; biological signal transduction; cell cell interaction; cell differentiation; cell growth regulation; cell migration; chemokine; chemokine receptor; developmental genetics; developmental neurobiology; embryo /fetus; embryogenesis; ganglions; genetic regulation; neuroanatomy; neurogenetics; neuroimaging; neuronal guidance; neurons; neuropeptides; neuroregulation; protein localization; protein structure function; trigeminal nerve; zebrafish

DESCRIPTION (provided by applicant): The sensory ganglia of the peripheral nervous system provide information about the environment to the central nervous system. The long-range goal of our research is to determine how sensory ganglia develop. The main focus will be on the trigeminal sensory ganglia, an assembly of neurons in the vertebrate head that mediate touch, temperature and pain sensations. Injuries and malformations of the trigeminal nerve are clinically and cosmetically devastating and are often associated with trigeminal neuralgia, a severe and recurrent neuropathic facial pain syndrome. Despite its important role, it is still poorly understood how the trigeminal ganglion develops. Using zebrafish as a model system, the earliest steps of trigeminal ganglion development will be analyzed by combining in vivo imaging of fluorescently labeled neurons and axons with embryological and genetic manipulations. Specific Aim 1 will determine how the ganglion is assembled from neuronal precursors. We will test the hypothesis that short-range chemokine signaling and neuron-neuron interactions regulate the location and clustering of trigeminal ganglion neurons. Specific Aim 2 will examine how the peripheral axons of the trigeminal ganglion come to cover and partition the receptive area of the head epidermis. We will determine how axon-axon interactions determine the direction of axon outgrowth and sculpt the axon arborization pattern of the trigeminal ganglion. The role and interaction of guidance signals in trigeminal ganglion assembly and axon arborization will be analyzed. These studies will contribute to our understanding of ganglion development and provide insights into the mechanisms through which neurons assemble and partition receptive areas, two fundamental issues in developmental neurobiology.

描述（由申请人提供）：周围神经系统的感觉神经节向中枢神经系统提供有关环境的信息。我们研究的长期目标是确定感觉神经节如何发育。主要关注点是三叉神经感觉神经节，这是脊椎动物头部中调节触觉、温度和疼痛感觉的神经元集合。三叉神经的损伤和畸形在临床和美容上具有破坏性，并且通常与三叉神经痛（一种严重的复发性神经性面部疼痛综合征）相关。尽管发挥着重要作用，但人们对三叉神经节如何发育仍知之甚少。使用斑马鱼作为模型系统，通过将荧光标记的神经元和轴突的体内成像与胚胎学和遗传操作相结合，分析三叉神经节发育的最早步骤。具体目标 1 将确定神经节如何由神经元前体组装而成。我们将检验短程趋化因子信号传导和神经元-神经元相互作用调节三叉神经节神经元的位置和聚集的假设。具体目标 2 将检查三叉神经节的外周轴突如何覆盖和分隔头部表皮的接受区域。我们将确定轴突-轴突相互作用如何决定轴突生长的方向并塑造三叉神经节的轴突树枝化模式。将分析引导信号在三叉神经节组装和轴突树枝化中的作用和相互作用。这些研究将有助于我们对神经节发育的理解，并深入了解神经元组装和划分感受区的机制，这是发育神经生物学中的两个基本问题。