Development of the Sense of Taste

描述（由申请人提供）：味觉领域已经确定了几种调节分子，这些分子指导真菌状乳头的发育，真菌状乳头是舌头前部味蕾的感觉器官。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，真菌状乳头形成与无乳头的舌区基因表达的具体差异尚未探讨。本应用着重于这样一个概念，即只有了解舌头特定区域和真菌状乳头隔室的基因表达和蛋白质定位，才能清楚地了解乳头的发育是如何被调节的。舌区和乳头区室是整合信号以平衡细胞增殖或分化反应的生理单位。因此，细胞信号传导是在特定区室的范围内进行的，然后这些区室来回发出信号来定义乳头的诱导、发育和分化。工作假设是，重要的形态原Sonic hedgehog通过以下途径以浓度依赖的方式控制真菌状乳头的发育：(a)信号传导调节特定区室和舌区的细胞增殖；(b)与其他信号分子家族的相互作用。验证该假设的方法包括使用报告小鼠和转基因小鼠；舌器官培养；基因阵列;以及通过转染和电穿孔敲除sirna的基因。三个特定的目标是：重要的形态原，Sonic hedgehog (Shh)，在细胞增殖与分化中的探测阶段和室特异性作用。定义和探索室特异性基因在发育中的舌头和舌头培养中的作用，比较乳头充满、乳头过剩、乳头抑制或无乳头的舌头组织。确定Shh、无翼蛋白（Wnt）和骨形态发生蛋白（Bmp）家族之间的相互作用。研究将为理解真菌状乳头的形成增加至关重要的深度；深度对于了解乳头和味觉细胞的特定区室是如何产生的至关重要。反过来，关于乳突分化过程中信号室的知识对于探索特定味觉细胞构成的起源、乳突和味觉细胞更新的控制以及乳突和味觉细胞在发育过程中的可塑性等问题至关重要。这些知识对于获取味觉如何产生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：味觉是生命所必需的，在指导识别和摄入或排斥营养物质。味蕾位于舌头的味道乳头中，这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。为了理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食物偏好和厌恶，我们需要了解味道乳头感觉器官是如何发育的。有必要了解乳头发育的哪些时期是严格确定的，哪些时期容易受到母体摄入或进入胎盘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有助于了解味蕾-感觉神经相互作用的形成，这种相互作用建立了味觉的神经回路。

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.