Taste organs: formation and regulation

味觉器官：形成和调节

• 批准号: 8436892
• 负责人: Hongxiang Liu
• 金额: $ 14.5万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 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 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8436892
• 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

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）：味蕾细胞是将化学刺激转化为神经信号传递给中枢神经系统的感觉末端器官，位于哺乳动物舌头的味觉乳头中。因此，味觉乳头承载的上皮将分化为包括味蕾细胞。然而，味觉生物学领域缺乏一个完整的理解：(1)什么构成可能的味觉细胞前体在发育乳头；(2)前体细胞在舌上皮中如何以及何时分化为味觉乳头和味蕾细胞表型；(3)在舌乳头和味蕾发育过程中，间充质如何以及通过哪些因素向舌上皮传递信号。我们关于神经嵴（NC）衍生细胞在舌上皮中的分布，以及间充质NC衍生细胞遗传修饰引起的舌乳头和味觉乳头的表型改变的初步数据表明，神经嵴在味觉器官的形成过程中对上皮和间充质都有贡献。Cre介导的、组织特异性的、基因标记和修饰为这些细胞谱系分析和功能分析提供了强大的工具。两种具有良好特征的转基因小鼠系用于NC检测，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（在P0-Cre中丰富，在Wnt1-Cre中很少），这表明味觉细胞可能是NC衍生的，这导致了该领域的一个新概念。P0-Cre标记的细胞优先