Development of the Sense of Taste

味觉的发展

• 批准号: 7878551
• 负责人: CHARLOTTE M MISTRETTA
• 金额: $ 32.39万
• 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/7878551
• 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 Preferences; Fungiform Papilla; Gene Expression; Gene Expression Profile; 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; Proteins; 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; public health relevance; receptor; residence; response; tongue papilla; transcription factor

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: The sense of taste is life-essential, in directing identification and ingestion or rejection of nutrients. Taste buds reside, in the tongue, in taste papillae which are complex sensory organs. Thus developing papillae contain cell and molecular information that ultimately determines taste bud formation. To understand the developmental origins of nutrient selection, and the extent to which genetic makeup or early food experience can determine food preferences and aversions, basic knowledge is needed about how the taste papilla sense organs develop. It is necessary to know what periods of papilla development are rigidly determined and what periods are vulnerable to influence from substances that cross the placenta after maternal ingestion or access. Understanding the basic developmental biology of taste papillae also will provide insight into formation of taste bud-sensory nerve interactions that set up the neural circuits for taste sensation.

描述（由申请人提供）：味觉领域已经鉴定了指导菌状乳头发育的几种调节分子：味蕾在前舌上的感觉器官驻留。然而，乳头味觉器官的复杂性，由特定的信号室组成，包括上皮和结缔组织，一直被忽视。此外，在菌状乳头形成与无乳头舌区基因表达的具体差异尚未探讨。这个应用程序的重点是概念，只有与知识有关的基因表达和蛋白质定位在特定区域的舌头和菌状乳头的车厢可以清楚地了解出现乳头的发展是如何调节。舌区和乳头区室是整合信号以平衡增殖或分化的细胞反应的生理单位。因此，细胞信号传导在特定隔室的范围内进行，然后来回发出信号以定义乳头诱导、发育和分化。工作假设是，重要的形态发生素Sonic hedgehog以浓度依赖性方式控制菌状乳头发育，通过：（a）信号传导以调节特定隔室和舌区域中的细胞增殖;以及（B）与信号传导其他分子家族的相互作用。检验这一假设的方法包括使用报告基因和转基因小鼠;舌器官培养;基因阵列;以及通过转染和电穿孔用siRNA敲除基因。三个具体目标是：探针阶段和车厢的重要形态，刺猬（嘘），在细胞增殖与分化的具体作用。定义，并探讨在发展中的舌和舌文化，比较舌组织的条件下，乳头充满，乳头过剩，乳头抑制，或乳头无区室特异性基因的作用。确定Shh，Wingless（Wnt）和Bone Morphogenetic Protein（Bmp）家族之间的相互作用。研究将增加重要的深度，了解菌状乳头的形成;深度是必不可少的，知道如何乳头和味觉细胞的具体隔间出现。反过来，乳头分化中的信号室的知识是追求特定的味觉细胞构成的起源，乳头和味觉细胞更新的控制，以及乳头和味觉细胞在发育过程中的可塑性问题的基础。这些知识对于获得有关味觉如何出现的基本信息至关重要，最终指导我们的饮食和食物选择。公共卫生相关性：味觉是生命的基本，在指导识别和摄取或拒绝营养。味蕾位于舌头的味觉乳头中，是一种复杂的感觉器官。因此，发育中的乳头包含最终决定味蕾形成的细胞和分子信息。为了了解营养选择的发育起源，以及基因组成或早期食物经验在多大程度上决定了食物偏好和厌恶，需要了解味觉乳头感觉器官如何发育的基本知识。有必要知道乳头发育的哪个时期是严格确定的，哪个时期容易受到母体摄入或进入后穿过胎盘的物质的影响。了解味觉乳头的基本发育生物学也将提供深入了解味蕾感觉神经相互作用的形成，建立味觉神经回路。