MOLECULAR GENETICS OF SENSORY GANGLIA DEVELOPMENT

描述（由申请人提供）：外周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。主要的焦点将集中在三叉神经感觉神经节上，这是脊椎动物头部神经元的集合，它们介导触觉、温度和疼痛感觉。三叉神经的损伤和畸形在临床上和美容上都是毁灭性的，并且通常与三叉神经痛相关，三叉神经痛是一种严重的复发性神经性面部疼痛综合征。尽管它的重要作用，它仍然是知之甚少三叉神经节如何发展。使用斑马鱼作为模型系统，三叉神经节发育的最早阶段将通过结合胚胎学和遗传操作的荧光标记的神经元和轴突的体内成像进行分析。具体目标1将确定神经节是如何从神经元前体组装的。我们将检验短距离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划分头部表皮的感受区。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分支模式。引导信号在三叉神经节组装和轴突分支中的作用和相互作用将被分析。这些研究将有助于我们了解神经节的发展，并提供深入了解神经元组装和分区接受区的机制，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.