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

项目概要/摘要味蕾细胞是一种感觉末端器官，可将化学刺激转化为神经信号，并传递到大脑中枢神经系统，存在于哺乳动物舌头的味觉乳头中。因此，味觉乳突承载着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了解：（1）发育中的乳头中可能的味觉细胞前体是由什么构成的； (2) 如何以及何时前体细胞在舌上皮中分化以获得味乳头和味蕾细胞表型；和（3）底层间质如何以及通过什么因素向乳头和味蕾的舌头上皮发出信号发展。我们关于舌上皮神经嵴衍生细胞 (NCDC) 分布和表型的初步数据间充质 NCDC 基因修饰引起的舌头和味觉乳头的改变表明神经嵴对味觉器官形成中的上皮和间质都有贡献。 Cre介导，组织特异性、基因标记和修饰为这些细胞谱系测定和功能分析。用于神经嵴测定的两个经过充分表征的转基因小鼠品系，Wnt1-和 P0-Cre，被使用。我们发现：（1）在舌上皮中，P0-Cre标记的NCDC首先分布在单个、 E11.5-12.5 的分散元素后来在味乳头和味蕾中形成聚集模式。本土化味蕾中 P0-Cre 标记的细胞表明味觉细胞的神经嵴衍生。我们建议单身人士，分散的 P0-Cre 标记的上皮细胞是神经嵴前体细胞，它们将经历细胞分化味乳头和味蕾中的特定细胞类型。 (2) 在舌间充质中，Wnt1-和P0-Cre均被标记 NCDC 与味乳头和味蕾密切相关。 Wnt1- 和 P0-Cre 驱动，条件遗传 I 型受体 Alk2 对骨形态发生蛋白 (BMP) 的修饰并显着改变舌头和味觉乳头的发育，表明舌头间充质通过 BMP 信号传导相互作用与乳头分化中的上皮细胞一起。拟议的研究将利用现代技术解决味觉乳头器官形成的基本问题。技术（Cre 介导的遗传修饰）以及体内和体外研究的结合。我们的目标是目的：（目标 1）证明神经嵴细胞何时何地迁移到舌上皮或原基；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；什么类型和部分味蕾细胞源自神经嵴；（目标 2）表征舌头间质如何，通过间充质 NCDC 中特定受体的 BMP 信号传导，与上皮细胞相互作用舌头和味觉乳头的发育。总体而言，拟议的研究旨在证明细胞起源、分化和间质相互作用味乳头和味蕾将有助于理解味觉器官的发育，并将带来新的神经嵴对味乳头和味蕾细胞的贡献领域的信息和新颖视角。关键词：舌头；味乳头；神经嵴衍生细胞