Taste organs: formation and regulation

味觉器官：形成和调节

基本信息

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
项目类别：
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

项目摘要

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

项目摘要/摘要味蕾细胞，将化学刺激转换为传达的神经信号的感觉末端器官中枢神经系统，居住在哺乳动物舌头的味觉乳头上。因此，品味乳头托管上皮将分化为包括味蕾细胞。但是，味觉生物学领域缺乏完整的理解：（1）哪些构成发展乳头状的味觉细胞前体；（2）如何以及何时前体在舌上皮中有区分，以获取味觉乳头和味蕾表型。（3）如何和通过哪些因素的基础间充质信号到乳头上的舌头上皮和味蕾发展。我们有关舌上皮和表型中神经rest衍生细胞（NCDC）分布的神经rest衍生细胞（NCDC）分布的初步数据在间充质NCDC中造成遗传修饰引起的舌头和味觉乳头的改变，表明神经rest对上皮和间质的贡献，形成器官的形成。 Cre介导的，组织特异性，遗传标记和修饰为这些细胞谱系测定和功能分析。两种特征良好的转基因小鼠系，用于神经rest测定法，Wnt1-和p0-cre，使用。我们发现：（1）在舌上上皮，p0-cre标记的NCDC首先以单个分布 E11.5-12.5处的散射元素稍后在味道乳头和味蕾中进行聚类。本地化味蕾中的P0-CRE标记的细胞表明味觉细胞的神经rest推导。我们建议单身散射的P0-CRE标记的上皮细胞是神经rest前体，这些细胞将经历细胞分化味觉乳头和味蕾的特定细胞类型。（2）在舌质中，wnt1-和p0-cre标记 NCDC与味觉乳头和味蕾密切相关。 WNT1和P0-CRE驱动的条件遗传用于骨形态发生蛋白（BMP）的I型受体ALK2修饰，并显着改变舌头和味道乳头的发展，表明舌质通过BMP信号传导相互作用与乳头分化的上皮上皮。拟议的研究将解决有关味觉乳头器官形成的基本问题技术（CRE介导的遗传修饰）和体内和体外研究的组合。我们的目标是至：（目标1）证明神经rest细胞在何时何地迁移到舌头或原始的上皮；这些细胞如何以及何时在舌上皮中分化以获取特定的细胞表型；什么类型和比例的味蕾细胞来自神经rest。（AIM 2）表征舌质的方式，通过BMP信号通过间充质NCDC中的特定受体进行信号，与上覆上皮相互作用舌头和品味乳头的发展。总体而言，提出的用于证明细胞起源，分化和间充质相互作用的研究品味乳头和味蕾将有助于理解味觉器官的开发，并带来新的信息和新颖的视野对味道乳头和味蕾细胞的神经rest贡献。关键词：舌头；品尝乳头；神经rest衍生的细胞