CONTROL OF OLFACTORY AND GUSTATORY NEURON REGENERATION

本提案中描述的研究的总体目标是了解 (I)发育和再生的化学感觉神经如何驾驭 通向其适当目标的路径；(2)当它们到达目标时， 它们停止生长和(Iii)它们如何改变它们的基因表达 成长模式向成熟模式转变，在这种模式下，它们形成了功能关系 与目标的关系。在味觉和嗅觉系统中，我们建议 无论是神经生长的环境还是靶子 结构提供了调节生长和成熟行为的信号 很有胆量。这些信号可能包括导航引导提示， “停止生长”信号，以及导致基因表达变化的信号。 在大鼠舌上，有2条感觉神经、舌质(LP)支。 三叉神经和鼓索(CT)为真菌样神经支配 乳头状。在发育过程中，它们同时进入舌头，但 指向不同的目标。CT支配关节的根尖。 菌状乳头，而LP支配这些区域的其他区域 结构，以及前舌的剩余部分。我们建议 识别将这些神经导向不同方向的导航信号 通过：(1)绘制菌状乳头中的靶点 可能促进(或抑制)神经的细胞外基质(ECM)分子 生长；(2)识别生长和再生过程中的表面分子 舌头上的感觉神经，可能作为当前信号的接收器 在环境中或在突触靶点上；(3)识别阳性和 轴突生长的负向信号和停止信号 舌头发育；(4)识别改变基因表达的信号 味觉神经元。含有环状乳头的味蕾是 由舌咽神经支配的。因为味觉和 舌咽神经中的躯体感觉神经来自两个不同的 在大鼠的神经节中，我们也将能够检查其中的一些问题 环状乳头的神经支配。在嗅觉系统中，我们 建议(1)识别嗅轴突的“停止生长”信号；(2) 识别可溶的或与膜相关的可改变的球部信号 嗅觉神经元的基因表达。体内和体外方法 将会被使用。

The broad goal of the research described in this proposal is to understand (i) how developing and regenerating chemosensory nerves navigate their paths to their appropriate targets; (ii) how, when they reach the targets, they stop growing and (iii) how they alter their gene expression from a growth mode to a mature mode in which they form a functional relationship with the target. In both the taste and the olfactory systems we suggest that both the environment through which the nerve growth and the target structures provide signals that regulate the behavior of growing and mature nerve. These signals are likely to include navigational guidance cues, "stop growth" signals, and signals that induce changes in gene expression. In the rat tongue, 2 sensory nerves, the lingual proper (LP) branch of the trigeminal, and the chorda tympani (CT) provide innervation to fungiform papillae. During development they enter the tongue simultaneously but are directed to different targets. The CT innervates the apices of the fungiform papillae whereas the LP innervates other regions of these structures, as well as the remainder of the anterior tongue. We propose to identify the navigational signals directing these nerves to different targets in the fungiform papilla by; (1) mapping the distribution of extracellular matrix (ECM) molecules that might promote (or inhibit) nerve growth; (2) identifying surface molecules on growing and regenerating sensory nerves in the tongue that might act as receptors of signals present in the environment or on the synaptic target; (3) identifying positive and negative tropic signals and stop signals for axonal growth in the developing tongue; (4) identifying signals that alter gene expression in gustatory neurons. The taste bud containing circumvallate papilla is innervated by the glossopharyngeal nerve. Because gustatory and somatosensory nerves in the glossopharyngeal nerve arise from two distinct ganglia in the rat we will also be able to examine some of these issues in the innervation o the circumvallate papilla. In the olfactory system we propose (1) to identify the "stop growth" signal for olfactory axons; (2) to identify soluble or membrane-associated bulbar signals that act to alter gene expression in olfactory neurons. Both in vivo and in vitro methods will be used.