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Neurotrophin receptor regulation of taste development

味觉发育的神经营养蛋白受体调节

基本信息

批准号：
8246445
负责人：
Robin Frances Krimm
金额：
$ 26.55万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8246445
关键词：
Adult Afferent Neurons Axon Binding Birth Brain-Derived Neurotrophic Factor Cell Count Cell Cycle Data Development Developmental Process Docking Embryonic Development Epithelium Fiber Fungiform Papilla Genes Genetic Goals Growth Growth Factor Immunohistochemistry Injury Intracellular Signaling Proteins Knockout Mice Maintenance Mediating Molecular Mus Mutate NTF3 gene Natural regeneration Nerve Nerve Growth Factor Receptors Nerve Regeneration Nervous System Trauma Neurites Neuronal Differentiation Neurons Neurotrophic Tyrosine Kinase Receptor Type 2 Palate Pathway interactions Pattern Peripheral Phospholipase Phosphorylation Site Receptor Protein-Tyrosine Kinases Receptor Signaling Regulation Research Role Scanning Electron Microscopy Sensory Sensory Ganglia Signal Pathway Signal Transduction Site System Systems Development Taste Buds Taste Perception Techniques Testing Therapeutic Uses Time Tongue Tyrosine Wild Type Mouse adapter protein axon regeneration improved in vivo nerve supply neuron development neuron loss neuronal survival neurotrophic factor neurotrophin 4 postnatal receptor reinnervation relating to nervous system research study response somatosensory synaptogenesis tool transcriptional coactivator p75

项目摘要

Project Summary: During development, sensory innervation to taste buds is tightly regulated by the actions of two neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4). Although both of these factors regulate gustatory innervation, their specific functions are different from one another. BDNF is expressed in gustatory epithelium and determines whether gustatory neurons will locate and innervate taste placodes during development, while NT4 does not. Both BDNF and NT4 regulate gustatory neuron and taste bud number, but they have their influences at different times during development. The long range goal of this research is to understand the cellular and molecular mechanisms that regulate the neural innervation to and the maintenance of taste buds during development. The proposed studies focus on mechanisms by which these two neurotrophins, BDNF and NT4, can influence various aspects of neural innervation through the same receptors, TrkB and p75. The proposed studies use cell counting, tract tracing, immunohistochemistry and scanning electron microscopy in gene knockout mice to determine when TrkB and p75 are required for specific aspects of gustatory development, including axonal extension into the tongue, target selection, and geniculate neuron/taste bud survival. Furthermore, these studies combine these anatomical approaches with sophisticated genetic tools allowing the function of single phosphorylation sites on the TrkB receptor protein to be blocked in vivo. These experiments will determine which TrkB intracellular signaling pathways are required for axonal extension into the tongue, target selection, and geniculate neuron/taste bud survival. Together these studies test the hypotheses that TrkB mediates the effects of both BDNF and NT4, but that each function of these neurotrophins requires a different intracellular signaling pathway. While p75's, more subtle role, is to modulate the regulation of gustatory development by neurotrophins. Because these experiments examine the fundamental mechanisms of how neurotrophins regulate neuronal survival and axon targeting via Trk receptors, this project has important implications for the therapeutic use of these signaling mechanisms in controlling neuron survival and axon targeting during regeneration. .

项目概述：在发育过程中，味蕾的感觉神经支配受到脑源性神经营养因子（脑源性神经营养因子）和神经营养因子-4（NT 4）这两种神经营养因子的作用。虽然这两种因素都调节味觉神经支配，但它们的具体功能与彼此BDNF在味觉上皮中表达，并决定味觉神经元是否将在发育过程中定位和支配味觉基板，而NT 4不。BDNF和NT 4 调节味觉神经元和味蕾数量，但它们的影响在不同的时间，发展这项研究的长期目标是了解细胞和分子调节神经支配和维持味蕾的机制，发展拟议的研究集中在这两种神经营养因子，BDNF 和NT 4，可以通过相同的受体TrkB和第75页。建议的研究使用细胞计数，束示踪，免疫组织化学和扫描在基因敲除小鼠中进行电子显微镜检查，以确定何时需要TrkB和p75进行特异性味觉发育方面，包括轴突延伸到舌头，目标选择，膝状体神经元/味蕾存活。此外，这些研究结合了联合收割机的这些解剖结构，使用复杂的遗传工具的方法，允许单个磷酸化位点的功能， TrkB受体蛋白在体内被阻断。这些实验将确定哪些TrkB细胞内信号通路是轴突延伸到舌、靶选择和膝状体所必需的。神经元/味蕾存活。这些研究共同验证了TrkB介导以下效应的假设： BDNF和NT 4，但这些神经营养因子的每种功能都需要不同的细胞内信号通路而p75的作用更为微妙，是调节味觉的调节，神经营养因子的发育因为这些实验研究了神经营养因子如何通过Trk受体调节神经元存活和轴突靶向，该项目这些信号传导机制在控制神经元中的治疗用途的重要意义存活和再生过程中的轴突靶向。 .