MOLECULAR GENETICS OF SENSORY GANGLIA DEVELOPMENT

描述(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是如何发育的。主要焦点将放在三叉神经感觉神经节上，三叉神经节是脊椎动物头部的神经元集合，负责调节触摸、温度和痛觉。三叉神经的损伤和畸形在临床上和美容上都是毁灭性的，经常与三叉神经痛有关，三叉神经痛是一种严重的复发性神经性面部疼痛综合征。尽管三叉神经节具有重要的作用，但三叉神经节是如何发育的仍然知之甚少。以斑马鱼为模型系统，将荧光标记的神经元和轴突的体内成像与胚胎学和遗传学操作相结合，将分析三叉神经节发育的最早步骤。具体目标1将决定神经节是如何由神经元前体组装起来的。我们将检验这一假设，即短程趋化因子信号和神经元-神经元相互作用调节三叉神经节神经元的位置和聚集。具体目标2将研究三叉神经节的外周轴突如何覆盖和分割头部表皮的接受区。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模式。将分析引导信号在三叉神经节组装和轴突树枝形成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，并为神经元组装和划分感受区的机制提供见解，这是发育神经生物学中的两个基本问题。

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.