Taste organs: formation and regulation

味觉器官：形成和调节

• 批准号: 8709030
• 负责人: Hongxiang Liu
• 金额: $ 22.72万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8709030
• 关键词: Address; Anterior; Biological Assay; Biological Models; Biology; Bone Morphogenetic Proteins; Cell Differentiation process; Cell Lineage; Cells; Cephalic; Chemicals; Data; Derivation procedure; Development; Elements; Embryo; Epithelial; Epithelial Cells; Epithelium; Fungiform Papilla; Gene Expression; Genetic; Genetic Recombination; Goals; Homeostasis; In Vitro; Ingestion; Knowledge; Label; Life; Link; Location; Mammals; Maps; Mediating; Mesenchymal; Mesenchymal Differentiation; Mesenchyme; Modification; Molecular; Monitor; Mus; Neural Crest; Neural Crest Cell; Neuraxis; Nutrient; Organ; Pathway interactions; Pattern; Phenotype; Primordium; Quality of life; Receptor Signaling; Regulation; Role; Sensory; Signal Pathway; Signal Transduction; Stimulus; Taste Bud Cell; Taste Buds; Taste Disorders; Taste Perception; Techniques; Tissue Recombination; Tissues; Tongue; Transgenic Mice; abstracting; base; bone morphogenetic protein receptor type I; bone morphogenetic protein receptors; cell motility; cell type; density; early embryonic stage; in vivo; novel; precursor cell; receptor; relating to nervous system; tongue papilla; tool

Project Summary/Abstract Taste bud cells, the sensory end organs that transduce chemical stimuli into neural signals conveyed to the central nervous system, reside in taste papillae in the mammalian tongue. Therefore, taste papillae host the epithelium that will differentiate to include taste bud cells. However, the field of taste biology lacks a complete understanding of: (1) what constitutes possible taste cell precursors in developing papillae; (2) how and when the precursors differentiate in lingual epithelium to acquire taste papilla and taste bud cell phenotypes; and (3) how and via what factors the underlying mesenchyme signals to tongue epithelium in papilla and taste bud development. Our preliminary data on neural crest derived cell (NCDC) distributions in lingual epithelium, and of phenotypic alterations of tongue and taste papillae induced by genetic modifications in mesenchymal NCDCs, suggest neural crest contributions to both epithelium and mesenchyme in the formation of taste organs. Cre-mediated, tissue-specific, genetic labeling and modifications provide powerful tools for these cell lineage assays and functional analyses. Two well-characterized transgenic mouse lines for neural crest assays, Wnt1- and P0-Cre, are used. We have found that: (1) In tongue epithelium, P0-Cre labeled NCDCs are first distributed in single, scattered elements at E11.5-12.5 to a clustered pattern later in taste papillae and taste buds. The localization of P0-Cre labeled cells in taste buds indicate a neural crest derivation of taste cells. We propose that the single, scattered P0-Cre labeled epithelial cells are neural crest precursors and these will undergo cell differentiation to specific cell types in taste papillae and taste buds. (2) In tongue mesenchyme, both Wnt1- and P0-Cre labeled NCDCs are closely associated with taste papillae and taste buds. Wnt1- and P0-Cre driven, conditional genetic modifications of type I receptor Alk2 for bone morphogenetic proteins (BMPs) and significantly alter the development of tongue and taste papillae, suggesting that tongue mesenchyme, via BMP signaling, interacts with the overlying epithelium in papilla differentiation. The proposed studies will address fundamental issues about formation of the taste papilla organ, using modern techniques (Cre-mediated genetic modifications) and combination of in vivo and in vitro studies. Our goals are to: (Aim 1) demonstrate where and when neural crest cells migrate to the epithelium of tongue or primordium; how and when these cells differentiate in lingual epithelium to acquire specific cell phenotypes; what types and proportions of taste bud cells are derived from neural crest; (Aim 2) characterize how the tongue mesenchyme, via BMP signaling through specific receptors in mesenchymal NCDCs, interacts with the overlying epithelium in the development of tongue and taste papillae. Overall, the proposed studies for demonstration of cell origin, differentiation and mesenchymal interactions in taste papillae and taste buds will contribute to understanding development of the taste organ and will bring new information and novel perspectives to the field for neural crest contributions to taste papillae and taste bud cells. Key words: tongue; taste papillae; neural crest derived cells

项目总结/摘要 味蕾细胞是将化学刺激转化为神经信号的感觉末端器官， 中枢神经系统，位于哺乳动物舌头的味觉乳头中。因此，味觉乳头 将分化为包括味蕾细胞的上皮。然而，味觉生物学领域缺乏完整的 理解：（1）什么构成了乳头发育中可能的味觉细胞前体;（2）如何以及何时 前体在舌上皮中分化以获得味觉乳头和味蕾细胞表型;以及（3） 舌乳头和味蕾中的间充质如何以及通过什么因素向舌上皮发出信号 发展 我们对舌上皮中神经嵴衍生细胞（NCDC）分布的初步数据， 间充质NCDCs中遗传修饰诱导的舌和味觉乳头的改变表明， 神经嵴在味觉器官形成中对上皮和间充质的作用。Cre介导， 组织特异性的遗传标记和修饰为这些细胞谱系测定提供了有力的工具， 功能分析用于神经嵴测定的两个良好表征的转基因小鼠系，Wnt 1-和P0-Cre， 被使用。我们发现：（1）在舌上皮中，P0-Cre标记的NCDCs首先以单个， 在E11.5-12.5时，在味觉乳头和味蕾中呈散在分布，随后呈簇状分布。国产化 P0-Cre标记的味蕾细胞表明味觉细胞的神经嵴起源。我们建议， 散在的P0-Cre标记的上皮细胞是神经嵴前体细胞，这些细胞将经历细胞分化， 味觉乳头和味蕾中的特定细胞类型。(2)在舌间质中，Wnt 1-和P0-Cre均被标记， NCDC与味觉乳头和味蕾密切相关。Wnt 1和P0-Cre驱动，条件遗传 骨形态发生蛋白（BMP）的I型受体Alk 2的修饰，并显著改变了骨形成蛋白（BMP）的表达。 舌和味觉乳头的发育，表明舌间充质，通过BMP信号， 在乳头分化中具有覆盖的上皮。 这项研究将利用现代生物技术， 技术（Cre介导的遗传修饰）和体内和体外研究的组合。我们的目标是 目的：（1）明确神经嵴细胞向舌上皮或原基迁移的位置和时间; 这些细胞如何以及何时在舌上皮中分化以获得特定的细胞表型; 味蕾细胞的比例来源于神经嵴;（目的2）表征舌间充质， 通过间充质NCDC中的特异性受体的BMP信号传导，与上覆上皮相互作用， 舌头和味觉乳头的发育。 总体而言，为证明细胞起源、分化和间充质相互作用而提出的研究， 味觉乳头和味蕾将有助于理解味觉器官的发育，并将带来新的 信息和新的观点，该领域的神经嵴的贡献，味觉乳头和味蕾细胞。 关键词：舌;味乳头;神经嵴源性细胞