Taste organs: formation and regulation

味觉器官：形成和调节

基本信息

批准号：
8598468
负责人：
Hongxiang Liu
金额：
$ 37.29万
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/8598468
关键词：
ACVR1 gene Address 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 Genetic Genetic Recombination Goals Homeostasis In Vitro Ingestion Knock-out Knowledge Label Lead Life Link Location Maintenance Mammals Maps Mediating Mesenchymal Mesenchymal Differentiation Mesenchyme Midbrain structure Modification Molecular Monitor Mus Neural Crest Neural Crest Cell Neuraxis Nutrient Organ Pathway interactions Pattern Phenotype Primordium Quality of life Regulation Role Sensory Signal Pathway Signal Transduction Staging Stimulus Taste Bud Cell Taste Buds Taste Disorders Taste Perception Techniques Tissue Recombination Tissues Tongue Transgenic Mice base bone morphogenetic protein receptor type I bone morphogenetic protein receptors cell motility cell type density early embryonic stage hindbrain in vivo migration mouse model novel precursor cell public health relevance receptor relating to nervous system tongue papilla tool

ACVR1 gene Address 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 Genetic Genetic Recombination Goals Homeostasis In Vitro Ingestion Knock-out Knowledge Label Lead Life Link Location Maintenance Mammals Maps Mediating Mesenchymal Mesenchymal Differentiation Mesenchyme Midbrain structure Modification Molecular Monitor Mus Neural Crest Neural Crest Cell Neuraxis Nutrient Organ Pathway interactions Pattern Phenotype Primordium Quality of life Regulation Role Sensory Signal Pathway Signal Transduction Staging Stimulus Taste Bud Cell Taste Buds Taste Disorders Taste Perception Techniques Tissue Recombination Tissues Tongue Transgenic Mice base bone morphogenetic protein receptor type I bone morphogenetic protein receptors cell motility cell type density early embryonic stage hindbrain in vivo migration mouse model novel precursor cell public health relevance receptor relating to nervous system tongue papilla tool

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项目摘要

DESCRIPTION (provided by applicant): 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 (NC) derived cell distributions in lingual epithelium, and of phenotypic alterations of tongue and taste papillae induced by genetic modifications in mesenchymal NC derived cells, 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 NC assays, Wnt1-Cre and P0-Cre, are used. We have found that: (1) In tongue epithelium, both Wnt1-Cre and P0-Cre labeled NC derived cells are seen including taste papillae and taste buds (abundant in P0-Cre, infrequent in Wnt1-Cre) suggesting a potential NC derivation of taste cells which leads to a new concept in the field. P0-Cre labeled cells are first distributed in single, scattered elements at early stages to a clustered pattern later in taste papillae and taste buds. We propose that the single, scattered P0-Cre labeled epithelial cells are NC precursors and these will undergo cell differentiation to specific cell types in taste papillae and taste buds. (2) In tongue mesenchyme, Wnt1-Cre labeled NC derived cells are closely associated with taste papillae and taste buds. Wnt1-Cre driven, conditional genetic modifications of type I receptors Alk2 and Alk3 for bone morphogenetic proteins (BMPs) significantly alter the tongue, taste papilla and taste bud formation and maintenance in a level-, stage- and receptor-specific manner. This suggests that BMP signaling in tongue mesenchyme, via distinct receptors, interacts with the overlying epithelium for different roles in the development of tongue, taste papillae and taste buds. 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 the optimal stage (1a) and primary cranial region (midbrain or hindbrain) (1b) of NC cell migration into the epithelium of tongue primordium; when and how many these cells differentiate in lingual epithelium to acquire specific cell phenotypes (1c); what types and proportions of taste bud cells are derived from NC (1d); (Aim 2) characterize how the BMP signaling in tongue mesenchymal NC derived cells, via distinct type I receptors (ALK2 and ALK3), interacts with the overlying epithelium in the development and maintenance of tongue, taste papillae and taste buds, with genetic modifications to (2a) down-regulate BMP signaling activity with Wnt1-Cre driven conditional knockout of Alk2 or Alk3; and (2b) up-regulate BMP signaling with Wnt1-Cre driven conditional constitutive activation of each receptor. 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.

描述（由申请人提供）：味蕾细胞，将化学刺激转移到传递到中枢神经系统的神经信号的感觉端器官，居住在哺乳动物舌头的味觉乳头上。因此，味觉乳头含有上皮，该上皮将分化为包括味蕾细胞。但是，味觉生物学领域缺乏对以下原因的完全理解：（1）哪些构成了发育中的乳头状的味觉细胞前体；（2）前体如何以及何时在舌上皮中分化以获取味觉乳头和味蕾细胞表型；（3）如何和通过哪些因素的基础间充质信号与乳头上的舌上和味蕾的发育中的舌头上皮。我们关于舌上上皮中神经rest（NC）衍生的细胞分布的初步数据，以及在间充质NC衍生细胞中诱导的舌和味觉乳头状的表型改变，表明神经犯罪对味道organs形成的上皮细胞和中层的神经犯果贡献。介导的，组织特异性的遗传标记和修饰为这些细胞谱系测定和功能分析提供了强大的工具。使用了两个用于NC测定的特征良好的转基因小鼠系，Wnt1-CRE和P0-CRE。我们发现：（1）在舌上皮中，可以看到Wnt1-Cre和P0-Cre标记的NC衍生细胞，包括味觉乳头和味蕾（含有P0-CRE的味道乳头和味蕾，在Wnt1-Cre中很少见），这表明味觉细胞的潜在NC衍生物是在该领域引起新概念的味觉细胞。 P0-CRE标记的细胞首先在早期阶段分布在单个零星的元素中，以便在味觉乳头和味蕾中以聚集的方式分布。我们建议单个散布的P0-CRE标记的上皮细胞是NC前体，这些细胞将经历味觉乳头和味蕾中特定细胞类型的细胞分化。（2）在舌间充质中，WNT1-CRE标记的NC衍生细胞与味觉乳头和味蕾密切相关。 Wnt1-Cre驱动的，I型受体ALK2和ALK3的有条件遗传修饰用于骨形态发生蛋白（BMP），以水平，阶段和受体特异性方式显着改变舌头，味觉乳头状和味蕾的形成和维护。这表明，舌质中的BMP信号传导通过不同的受体与上覆的上皮相互作用，在舌头，味道乳头和味蕾的发展中发挥了不同的作用。拟议的研究将使用现代技术（CRE介导的遗传修饰）以及体内和体外研究的组合解决有关味觉乳头器官形成的基本问题。我们的目标是：（ AIM 1）证明NC细胞迁移到舌头上皮的NC细胞迁移的最佳阶段（1a）和原发性颅骨区域（中脑或后脑）（1b）；这些细胞何时何地分化在舌上皮中，以获取特定的细胞表型（1C）；味蕾细胞的哪些类型和比例来自NC（1D）； (Aim 2) characterize how the BMP signaling in tongue mesenchymal NC derived cells, via distinct type I receptors (ALK2 and ALK3), interacts with the overlying epithelium in the development and maintenance of tongue, taste papillae and taste buds, with genetic modifications to (2a) down-regulate BMP signaling activity with Wnt1-Cre driven conditional knockout of Alk2 or Alk3; （2B）用Wnt1-CRE驱动的每个受体的有条件组成型激活上调BMP信号传导。总体而言，拟议的有关味觉乳头和味蕾的细胞起源，分化和间充质相互作用的研究将有助于理解味觉器官的发展，并将为味道乳头乳头和味蕾细胞的神经rest贡献带来新的信息和新观点。