NERVE-TARGET CELL INTERACTION IN TASTE BUD MAINTENANCE

味蕾维持中的神经靶细胞相互作用

• 批准号: 6820959
• 负责人: MARK Celestin WHITEHEAD
• 金额: $ 29.47万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-04-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6820959
• 关键词: cell cell interaction; cell differentiation; cell line; chorda tympani; ganglion cell; gene targeting; genetically modified animals; growth factor receptors; hamsters; immunocytochemistry; in situ hybridization; innervation; laboratory mouse; nerve injury; nervous system regeneration; neural information processing; neural plasticity; neurogenesis; neurotrophic factors; receptor expression; taste buds

DESCRIPTION (provided by applicant): A key question in taste is how the system maintains a stable message about taste quality while receptor cells are turning over, constantly changing connections between the taste bud and its nerve fibers. To accomplish this the taste periphery must employ a high degree of receptoneural plasticity. We are beginning to understand the neurochemical basis of receptoneural plasticity in relation to the precision with which ganglion cells are connected to taste buds. Plasticity is most dramatic in the degeneration of taste buds when denervated, and their rapid regeneration when reinnervated. Evidence is growing that such neuron-target cell plasticity involves neurotrophins and their tyrosine kinase receptors. In hamster, the fungiform buds of which uniquely resist degeneration after denervation, we identified enrichments in BDNF, TrkB and TrkC not seen in vallate or foliate buds that do not resist denervation, e.g., neurotrophin-positive fungiform bud cells are uniquely unaffected by denervation. Conceivably, cells expressing these growth factors are involved in taste bud maintenance and in promoting nerve fiber in-growth. The possibilities that such maintenance involves increases in gemmal cell genesis to offset cell losses due to denervation, or influences on cell lifespan, will be evaluated by BrdU labeling. A role for neurotrophins in the targeting of nerve fibers will be explored with multicolored lipophilic dyes to demonstrate precisely the connectivity between small populations of ganglion cells and a single buds. Studies of taste bud neurotrophin expression in relation to denervation, reinnervation, gemmal cell genesis, and innervation patterns will emphasize analysis of the mouse. Mouse fungiform buds have uniquely discrete innervation patterns and express neurotrophins differently (e.g., less BDNF) than hamster buds. Species comparison allows formulation of hypotheses about the role of neurotrophins and receptors in taste bud maintenance and innervation. An existing BDNF epithelial overexpressing mouse line will be used to test the hypothesis that increased peri-bud neurotrophin results in denser, less discrete innervation and heightened bud cell genesis or lifespan. For comparison, bud-specific BDNF knockout mice will be generated to specifically test the effect of bud neurotrophin absence on innervation, reinnervation and gemmal cell differentiation. Additionally, an inducible BDNF bud knockout mouse will be generated to test the effect of BDNF loss.

描述（由申请人提供）：味觉中的一个关键问题是系统如何在受体细胞翻转时保持关于味觉质量的稳定信息，不断改变味蕾及其神经纤维之间的连接。为了实现这一点，味觉外围必须采用高度的感受神经可塑性。我们开始了解感受神经可塑性的神经化学基础，与神经节细胞与味蕾连接的精确性有关。可塑性是最戏剧性的味蕾退化时，去神经支配，并迅速再生时，重新神经支配。越来越多的证据表明，这种神经元-靶细胞可塑性涉及神经营养因子及其酪氨酸激酶受体。在仓鼠中，其真菌状芽在去神经支配后独特地抵抗退化，我们鉴定了在不抵抗去神经支配的卵形或叶状芽中未观察到的BDNF、TrkB和TrkC的富集，例如，神经营养素阳性菌状芽细胞独特地不受去神经支配的影响。可以想象，表达这些生长因子的细胞参与味蕾维持和促进神经纤维向内生长。这种维持涉及增加胚芽细胞发生以抵消由于去神经支配引起的细胞损失或对细胞寿命的影响的可能性，将通过BrdU标记进行评价。神经营养因子在靶向神经纤维中的作用将用多色亲脂性染料进行探索，以精确地证明小群体神经节细胞和单个芽之间的连接。味蕾神经营养因子表达与去神经支配、再神经支配、生殖细胞发生和神经支配模式的关系的研究将强调对小鼠的分析。小鼠菌状芽具有独特的离散神经支配模式，并以不同的方式表达神经营养因子（例如，比仓鼠芽更少的BDNF）。物种比较允许制定的假说的作用，神经营养因子和受体在味蕾的维护和神经支配。现有的BDNF上皮过表达小鼠系将用于测试增加的芽周神经营养因子导致更密集、更少离散的神经支配和提高的芽细胞发生或寿命的假设。为了比较，将产生芽特异性BDNF敲除小鼠以特异性测试芽神经营养因子缺失对神经支配、神经再支配和芽细胞分化的影响。此外，将产生诱导型BDNF芽敲除小鼠以测试BDNF损失的影响。