Eph/ephrin Signaling in Taste Nerve Development

味觉神经发育中的 Eph/ephrin 信号转导

• 批准号: 7073196
• 负责人: MICHAEL William ROCHLIN
• 金额: $ 21.08万
• 依托单位: LOYOLA UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7073196
• 关键词: afferent nerve; biological signal transduction; cell migration; central neural pathway /tract; chorda tympani; developmental neurobiology; embryo /fetus tissue /cell culture; ephrins; gene expression; genetically modified animals; laboratory mouse; neurogenesis; nucleic acid amplification techniques; peripheral nervous system; polymerase chain reaction; protein structure function; sensory mechanism; taste

DESCRIPTION (provided by applicant): The motile tips of embryonic axons integrate signaling information from a multitude of guidance molecules during development, plasticity, and regeneration following injury. The rodent taste system provides an especially attractive model in which to study these processes. Perhaps the earliest event in taste nerve development is the sorting of geniculate axons into one of two nerves that diverge from one another at a right angle as they exit the ganglion. No differences between these axons have been described. Cell- contact dependent processes have a prominent role in pathway and target discrimination, and could underlie the divergent signaling. Eph receptors and ephrins are implicated in contact-dependent axon divergence and target selection elsewhere both within the nervous system and in other tissues, but neither their expression nor their function has been explored in the taste system. Our preliminary data indicate that several members are expressed in the taste system. Approaches: (Aim 1) We will test the hypothesis that Eph/ephrins are differentially expressed among early embryonic sensory neurons that ultimately innervate well separated targets. To this end, nerve labeling will be carried out, and then cells from each of these populations will be microdissected and subjected to antisense RNA amplification and PCR, enabling us to profile up to 10 Eph/ephrin family members per cell. (Aim 2) We will perturb Eph/ephrin function in organ cultured embryos. We will place beads soaked in diffusible (Fc) constructs of these molecules near the ganglion to test their impact on nerve divergence.

描述（由申请人提供）：胚胎轴突的运动尖端在损伤后在发育，可塑性和再生过程中整合了许多引导分子的信号信息。啮齿动物味道系统提供了一个特别有吸引力的模型来研究这些过程。味觉神经发育中最早的事件也许是将晶状轴突分选为两条神经之一，当它们退出神经节时，它们以直角彼此差异。这些轴突之间没有差异。细胞接触依赖性过程在途径和目标歧视中具有重要作用，并且可能是信号传导的基础。 EPH受体和埃弗林与接触依赖性的轴突差异和神经系统和其他组织中其他地方的目标选择有关，但是在味觉系统中均未探索它们的表达和功能。我们的初步数据表明，在口味系统中表达了几个成员。方法：（目标1）我们将检验以下假设：以eph/ephrins在早期的胚胎感觉神经元中差异表达，这些神经元最终将良好的分离靶标支配。为此，将执行神经标记，然后将微分区分这些人群的细胞进行微解析并进行反义RNA扩增和PCR，从而使我们能够每个细胞的概况高达10 eph/ephrin家族成员。 （AIM 2）我们将在器官培养的胚胎中扰动EPH/Ephrin功能。我们将将浸泡在神经节附近的这些分子的扩散（FC）构建体中，以测试其对神经差异的影响。