The role of BDNF in taste receptor cell innervation

BDNF 在味觉受体细胞神经支配中的作用

• 批准号: 6523629
• 负责人: Robin Frances Krimm
• 金额: $ 14.3万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-26 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6523629
• 关键词: brain derived neurotrophic factor; chemoreceptors; ganglion cell; gene expression; genetically modified animals; immunocytochemistry; in situ hybridization; innervation; laboratory mouse; polymerase chain reaction; taste; taste buds

DESCRIPTION (provided by applicant): The neurotrophin (BDNF) is essential for the development and proper innervation of taste buds. Analysis of the taste system in wildtype and overexpresser transgenic mouse models has shown that BDNF acts, at least in part, as a target-derived factor that modulates axon targeting and innervation density. During early embryonic periods, BDNF is expressed in the epithelium of fungiform papillae. By later embryonic times BDNF expression in the tongue becomes focused and is only found in cells comprising developing taste buds. This refined expression pattern suggests that BDNF synthesis by taste bud cells is crucial for normal taste innervation. In support of this possibility, we found that transgenic mice that overexpress BDNF across the entire tongue epithelium had severely disrupted innervation to taste buds and fewer taste buds, even though these mice had more gustatory (geniculate) neurons. We now propose to advance this analysis and test how the level of BDNF in the taste bud itself affects neuron survival and innervation. This will be done using a new transgenic mouse model in which the keratin 19-gene promoter will be used to target BDNF gene expression to receptor cells of taste buds. Transgenic mice that overexpress K19 in taste cells (K19-BDNF mice) will be used to examine how target-derived BDNF modulates taste bud development and innervation. Specifically, we will use RT-PCR, in situ hybridization, retrograde labeling, and basic histological approaches to determine if enhanced expression of BDNF in taste cells, 1) increases innervation to fungiform papillae, 2) increases the size or number of taste buds in fungiform papillae, 3) disrupts the positive co-relation that exists between taste bud size and innervation, and 4) increases gelliculate ganglion cell survival. These mice will also provide a valuable model for studies on the receptor mechanisms and internal signaling pathways that underlie the action of BDNF in gustatory development. This approach provides a new and powerful means to manipulate gene expression in the taste end organs, allowing study of the intrinsic factors that regulate taste organ development and innervation.

描述（由申请人提供）：神经营养因子（BDNF）是必不可少的， 味蕾的发育和适当的神经支配。口味分析 野生型和过表达转基因小鼠模型中的系统表明，BDNF 至少部分地充当调节轴突靶向的靶源因子 和神经密度。在早期胚胎时期，BDNF表达于 菌状乳头的上皮。到胚胎后期BDNF表达 舌头中的细胞变得集中，并且仅在包括发育中的细胞中发现 味蕾这种精细的表达模式表明，BDNF的合成是通过 味蕾细胞对于正常的味觉神经支配至关重要。为支持这一 可能性，我们发现，过度表达BDNF的转基因小鼠， 整个舌上皮细胞对味蕾的神经支配受到严重破坏， 更少的味蕾，即使这些老鼠有更多的味觉（膝状体） 神经元我们现在建议推进这一分析，并测试BDNF的水平如何 影响神经元的存活和神经支配。这将是 使用一种新的转基因小鼠模型，其中角蛋白19基因启动子 将用于将BDNF基因表达靶向味蕾的受体细胞。 将使用在味觉细胞中过表达K19的转基因小鼠（K19-BDNF小鼠 研究靶源性BDNF如何调节味蕾发育， 神经支配具体而言，我们将使用RT-PCR、原位杂交、逆行 标记和基本的组织学方法，以确定是否增强表达 1）增加对菌状乳头的神经支配，2） 增加菌状乳头中味蕾的大小或数量，3）破坏 味蕾大小与神经支配之间存在正相关关系， 4)增加胶状神经节细胞存活。这些老鼠也将提供一个 为研究受体机制和内部信号传导提供了有价值的模型 这是脑源性神经营养因子在味觉发育中作用的基础。这 方法提供了一种新的和强有力的手段来操纵基因表达在 味觉末端器官，允许研究调节味觉的内在因素 器官发育和神经支配。