Development of the Sense of Taste

味觉的发展

• 批准号: 8277395
• 负责人: CHARLOTTE M MISTRETTA
• 金额: $ 31.35万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8277395
• 关键词: Anterior; Automobile Driving; Back; Biological; Bone Morphogenetic Proteins; Cell Proliferation; Cells; Complex; Connective Tissue; Constitution; Development; Developmental Biology; Diet; Differentiation and Growth; Electroporation; Embryo; Environment; Epithelial; Epithelium; Equilibrium; Erinaceidae; Esthesia; Family; Food; Food Aversion; Food Preferences; Fungiform Papilla; Gene Expression; Gene Expression Profile; Gene Proteins; Genes; Genetic; Goals; Ingestion; Knockout Mice; Knowledge; Laboratories; Lead; Life; Location; Mesenchymal; Mesenchyme; Molecular; Molecular Profiling; Mus; Nerve; Nucleic Acid Regulatory Sequences; Nutrient; Organ; Organ Culture Techniques; Pathway interactions; Pattern; Physiological; Placenta; Protein Family; Regulation; Relative (related person); Reporter; Reporter Genes; Role; Sense Organs; Sensory; Sensory Receptors; Signal Transduction; Staging; Stimulus; Taste Bud Cell; Taste Buds; Taste Perception; Testing; Tissues; Tongue; Transfection; Transgenic Mice; Work; afferent nerve; base; experience; human SMO protein; insight; morphogens; neural circuit; novel strategies; progenitor; receptor; residence; response; smoothened signaling pathway; sonic hedgehog receptor; tongue papilla; transcription factor

PROJECT SUMMARY The field of taste has identified several regulatory molecules that direct development of the fungiform papilla: the sense organ residence of taste buds on the anterior tongue. However, the complexity of the papilla taste organ, composed of specific signaling compartments and encompassing both epithelial and connective tissues, has been ignored. Furthermore, specific differences in gene expression in fungiform papilla-forming versus papilla-free tongue regions have not been explored. This application focuses on the concept that only with knowledge about gene expression and protein localization in particular regions of the tongue and compartments of the fungiform papilla can a clear understanding emerge about how papilla development is regulated. Tongue regions and papilla compartments are physiological units that integrate signals to balance cell responses of proliferation or differentiation. Thus, cell signaling proceeds in the confines of particular compartments that then signal back and forth to define papilla induction, development and differentiation. The working hypothesis is that the important morphogen, Sonic hedgehog controls fungiform papilla development, in a concentration dependent manner, through: (a) signaling to regulate cell proliferation in specific compartments and tongue regions; and, (b) interactions with signaling other molecular families. Approaches to test the hypothesis include use of reporter and transgenic mice; tongue organ cultures; gene arrays; and gene knockdown with siRNAs via transfection and electroporation. Three specifc aims are to: Probe stage and compartment specific roles for the important morphogen, Sonic hedgehog (Shh), in cell proliferation versus differentiation. Define, and explore roles for, compartment specific genes in the developing tongue and tongue cultures, comparing lingual tissues in conditions that are papilla-replete, papilla-superabundant, papilla-suppressed, or papilla-free. Determine interactions among Shh, Wingless (Wnt) and Bone morphogenetic protein (Bmp) families. Studies will add crucial depth to understanding fungiform papilla formation; depth that is essential to knowing how papilla- and taste cell- specific compartments arise. In turn knowledge about signaling compartments in papilla differentiation is fundamental to pursuing questions about the origins of specific taste cell constitution, control of papilla and taste cell renewal, and papilla and taste cell plasticity during development. This knowledge is essential for acquiring basic information about how taste sensation emerges, to ultimately direct our diet and food choices.

项目总结 味觉领域已经确定了几个指导真菌样发育的调节分子 乳头：味蕾在舌前部的感觉器官。然而，这个问题的复杂性 乳头状味觉器官，由特定的信号间隔组成，包括上皮性和 结缔组织，一直被忽视。此外，真菌样中基因表达的特异性差异 乳头形成舌区和无乳头舌区还没有被研究过。此应用程序侧重于 只有对基因表达和蛋白质在特定区域的定位有了解的概念 舌头和菌状乳头的间隔可以清楚地理解乳头是如何形成的 开发是受监管的。舌区和乳头间隔是整合的生理单位 平衡细胞增殖或分化反应的信号。因此，信元信令在 特定隔室的范围，然后来回发出信号以定义乳头的诱导、发育 和差异化。工作假说是，重要的形态因子，声波刺猬控制着 菌状乳头的发育依赖于浓度，通过：(A)信号调节细胞 在特定间隔和舌区的增殖；以及，(B)与其他信号的相互作用 分子家族。检验这一假说的方法包括使用报告和转基因小鼠；舌头 器官培养；基因阵列；以及通过转基因和电穿孔用siRNA敲除基因。三 具体目标是：探测阶段和隔室中重要的形态因子Sonic的特定作用 Hedgehog(Shh)，在细胞增殖与分化之间。定义和探索隔间的角色 发展中的舌头和舌头文化中的特定基因，比较条件下的舌头组织 乳头完整，乳头过多，乳头抑制，或无乳头。确定交互作用 在Shh、无翼(Wnt)和骨形态发生蛋白(BMP)家族中。研究将增加至关重要的深度 了解菌状乳头的形成；深度对于了解乳头-以及细胞的味道-是必不可少的 特定的隔间就会出现。反过来，关于乳头分化中的信号间隔的知识是 对于探索特定味觉细胞构成的起源、乳头和 味觉细胞更新，以及乳头和味觉细胞发育过程中的可塑性。这方面的知识对于 获取有关味觉如何产生的基本信息，最终指导我们的饮食和食物 选择。